Cancer

Diagnosis The stage is set for the diffusion of positron emission tomography (PET) in oncology A large body of evidence now attests to the diagnostic accuracy and cost-effectiveness of PET in oncology MJA 1999; 171: 527-528 Positron emission tomography (PET) is an exact, non-invasive technique for studying the body's biochemistry. The patient is injected with a positron-emitting radioisotope of a biologically active substance -- for oncological investigations, fluorodeoxyglucose (FDG) (2-deoxyglucose labelled with the positron emitter fluorine 18) is used.1,2 FDG is actively concentrated in cancer cells, and the PET camera detects the location of the FDG by registering the ejection of positrons from the nuclei of fluorine 18 atoms. As the positrons are ejected they collide with electrons; both particles annihilate and emit two 511 keV gamma rays at 180º to each other. Rings of detectors in PET cameras register these signals and the resulting images of particular organs, or the whole body, are displayed in three dimensions. Thus, PET can reveal the presence of cancer by recording an increased rate of glucose metabolism before any of the structural changes detectable by ultrasound, radiography, computed tomography (CT) and magnetic resonance imaging (MRI) have occurred. The history of PET in Australia is given in Box 1. Recognition of the utility of PET, particularly in cancer management, is reflected in its expanding applications around the world, and in the proportion of papers on PET (rising from 10% to 36%) presented at annual meetings of the US Society of Nuclear Medicine.3 The majority of these papers relate to its applications in oncology. Similarly, most clinical PET studies performed in Australia (over 80%) have been for cancer management.4 Box 2 gives a summary (adapted from Valk5) of the current role of PET in cancer management. Although these overseas studies demonstrate the superior diagnostic accuracy of PET in a wide range of applications in oncology, the article in this issue of the Journal by Hicks et al6 is the first extensive Australian report of the use of PET. The contributions of PET to patient management in oncology reported by Hicks and colleagues are similar to those recorded in the international literature. Hicks and colleagues did not assess cost-effectiveness as part of their audit of PET studies, but studies in other countries have provided a large body of evidence of the cost-effectiveness of PET in oncology. However, Valk emphasises that, while there are adequate cost-effectiveness data on diagnosis of pulmonary nodules and mediastinal staging of lung cancer, cost-effectiveness data for the use of PET in other conditions are incomplete.7 Cost-effectiveness studies have demonstrated that the benefits of PET include avoidance of unnecessary imaging procedures (radiography, CT, and MRI) and biopsies, as well as prevention of unnecessary surgery and hospitalisation.7-9 Influenced by the findings of diagnostic accuracy and cost-effectiveness, the US government has now included the oncology applications for PET studies detailed below among its Medicare reimbursement categories: Characterisation of solitary pulmonary nodule; and initial staging of non-small-cell carcinoma of the lung (since January 1998); and Colorectal cancer recurrence or metastasis; lymphoma staging and characterisation; melanoma recurrence or metastasis (since July 1999).10 In Australia, it is time to consider making PET available at additional sites, both to improve medical outcomes for a greater number of patients and to obtain our own cost-effectiveness data. Essential to this process are: A reliable supply of FDG; Acceptable instrumentation; Accredited PET staff (physicians, scientists and technologists); Appropriate locations for PET services; and Provision for ongoing evaluation. The current situation in Australia in relation to these critical factors is as follows. Fluorine-18 deoxyglucose (FDG) supply: In the past decade, Australia has made a multimillion dollar investment in cyclotrons -- the National Medical Cyclotron (NMC) in Sydney, operated by the Australian Nuclear Science and Technology Organisation (ANSTO), and two small cyclotrons in Melbourne. These cyclotrons can supply enough FDG to meet the present and immediate future needs of all capital cities except Perth and Darwin. If PET continues to expand, it may be necessary to install further regional cyclotrons. Acceptable instrumentation: The bulk of the evidence used by expert committees in the United States and Australia to determine existing reimbursement policies in PET in oncology came from PET studies using scanners equipped with bismuth germanate crystals (BGO). PET centres at Royal Prince Alfred Hospital and the Austin and Repatriation Medical Centre are equipped with BGO cameras, which remain the reference standard for FDG PET oncology studies. Further studies on cost-effectiveness need to be based on data obtained using comparable instruments. A range of instruments claiming similar performance exists, and there is an ongoing need for these to be evaluated. Accredited PET staff (physicians, scientists,11,12 technologists): Australia has a number of PET-trained physicians, scientists and technologists. This pool of expertise will need to be expanded and appropriate accreditation guidelines defined and implemented. Appropriate location of PET services: Delivery of advanced oncology therapy is centred predominantly in major hospitals which have comprehensive diagnostic services (eg, radiography, CT, MRI, nuclear medicine), a range of other specialties and radiation oncology planning and treatment services. The oncological dominance of clinical PET usage patterns automatically proposes centres such as these as logical sites for the diffusion of PET. Ongoing evaluation: Diffusion of PET services should be carried out in conjunction with the established, transparent evaluation processes. The oncology stakeholders, including patient advocacy groups, should be involved in the formulation and implementation of protocols. Liaison with the Medical Services Advisory Committee, the federal Department of Health and Aged Care and State and Territory health departments is essential. The Federal Department of Health and Aged Care is currently conducting a review of PET with input from a Medical Services Advisory Committee PET working party and involving existing PET providers. In addition, NSW and Victoria are conducting their own reviews of PET services. As well as demonstrating clinical utility, the study of Hicks et al shows the advantages that flow from locating PET facilities in major oncology referral centres. The model for the role of PET suggested here proposes the collocation of PET services in the nuclear medicine departments of comprehensive refer ral hospitals which have existing regional oncology services. The advantages of this proposal are that PET is located where the greatest number of oncology patients can benefit from its clinical accuracy, and further large-scale evaluations of its cost effectiveness can be undertaken. John G Morris, AO Professor of Clinical Medicine Australian Nuclear Medicine and PET Consultants, Sydney, NSW Sokoloff L, Reivich M, Kennedy C, et al. The [14C] deoxyglucose method of local cerebral glucose utilisation: Theory, procedure, and normal values in the conscious and anaethestised albino rat. J Neurochem 1977; 28: 897-916. Som P, Atkins HL, Bandoypadhyay D, et al. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): non-toxic tracer for rapid tumor detection. J Nucl Med 1980; 21: 670-675. Proceedings of the 46th Annual Meeting of the Society of Nuclear Medicine, Los Angeles, California, 1999. J Nucl Med 1999; 40 (Suppl): 5. Commonwealth Department of Health and Aged Care (Diagnostics and Technology Branch). Review of positron emission tomography (PET). Canberra: The Department, July 1999. Valk PE. Effect of FDG-PET on patient management and cost. Handout book. Reston, Va (USA): Society of Nuclear Medicine, 1999: 200-204. Hicks RJ, Binns DS, Fawcett ME, et al. Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner. Med J Aust 1999; 171: 529-532. Valk PE, Pounds TR, Tesar TD, et al. Cost-effectiveness of PET in clinical oncology. Nucl Med Biol 1996; 23: 737-743. Lowe VJ, Fletcher JW, Gobar L, et al. Prospective evaluation of positron emission tomography in lung nodules. J Clin Oncol 1998; 16: 1075-1084. Gambhir SS, Hoh CK, et al. Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med 1996; 37: 1428-1436. HCFA expands Medicare coverage of PET. J Nucl Med 1999; 50: 23N. Bailey DL, Miller MP, Spinks TJ, et al. Experience with fully 3D PET and implications for future high-resolution 3D tomographs. Phys Med Biol 1998; 43: 777-786. Hutton B. Emerging clinical applications of quantitative emission computed tomography. In: Pham B, Braun M, Maeder AJ, Eckert MP, editors. New approaches in medical image analysis, 1999. Proceedings of SPIE (International Society of Optical Engineering) 1999; 3747: 57-76. (ISBN 0-8194-3229-6.) 1: History of positron emission tomography in Australia In Australia, PET was first used in 1992 at the Royal Prince Alfred Hospital (RPAH), Sydney, and the Austin Hospital, in Melbourne (now the Austin and Repatriation Medical Centre). In 1993, the Federal Government, in conjunction with the New South Wales and Victorian governments, funded a five-year evaluation project involving PET units at these two sites. The intention was to undertake a rigorous evaluation of the effectiveness of PET as a diagnostic tool in Australian clinical practice and provide information on which to base decisions about future resource allocation. This project had difficulties in establishing appropriate protocols, and in October 1997 a modified evaluation strategy was adopted. This involved limited Medical Benefits Schedule (MBS) funding of the RPAH and Austin PET centres to develop evidence on the clinical role, value and cost effectiveness of PET. MBS reimbursement for oncology covered breast, gastrointestinal, genitourinary, head and neck, haematological, hepatobiliary, soft tissue and thoracic cancer. In 1996 and 1998, respectively, unfunded PET centres began operating at the Peter MacCallum Cancer Institute in Melbourne and the Wesley Hospital in Brisbane. Back to text2: Uses of positron emission tomography (PET) in oncology4 1. Primary tumour diagnosis Solitary pulmonary nodule Unknown primary tumour 2. Primary tumour staging Non-small-cell lung cancer Hodgkin's disease Breast cancer Oesophageal cancer 3. Recurrent tumour - diagnosis and staging Recurrent colorectal cancer Metastatic melanoma Recurrent head and neck cancer Other tumours: lymphoma, ovarian cancer, breast cancer, non-small-cell lung cancer 4. Treatment evaluation (surgical, chemotherapy, radiation therapy) Non-small-cell lung cancer Non-Hodgkin's lymphoma Recurrent head and neck cancer Hepatic recurrence of colorectal cancer Metastatic breast cancer Adapted from Society of Nuclear Medicine 1999 Handout Book, June 1999. Back to text

John G Morris

Diagnosis Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner Positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) is an accurate technique for staging and therapeutic monitoring in oncology. We evaluated our use of FDG PET in an oncology centre after our first 2500 studies, and summarise our experience of PET for the major referral indications. Optimised for clinical service, PET offers lower scanning costs and therefore improved cost-effectiveness. Rodney J Hicks, David S Binns, Meagan E Fawcett, Robert E Ware, Victor Kalff, Allan F McKenzie, John P Zalcberg and Lester J Peters MJA 1999; 171: 529-532 For related articles see Morris Introduction - Major referral indications - Providing cost-effective PET in oncology - Conclusion - Acknowledgements - References - Authors' details - - More articles on Oncology Introduction There is increasing recognition of the role of positron emission tomography (PET) in oncology, supplementing its established roles in the evaluation of myocardial viability1 and epilepsy.2 The radiopharmaceutical fluorine-18 fluorodeoxyglucose (FDG), an analogue of glucose, has high uptake in a wide range of tumours. FDG PET has been shown to be an accurate technique for tumour staging3 and for therapeutic monitoring.4However, the high establishment and operating costs of conventional PET facilities make economic justification more difficult than for cheaper imaging methods. Before funding new technologies, government and third-party payers increasingly require evidence of cost-effectiveness as well as diagnostic accuracy. High unit scanning costs demand substantially greater effectiveness. The development of lower-cost positron imaging systems over the past 10 years offers a realistic opportunity to expand the clinical availability of PET by improving this balance. Our PET facility, which uses such a system and is optimised for clinical service provision, was commissioned in September 1996. Our aim was to summarise our experience of PET scanning after the first 2500 FDG PET studies performed at our centre (Figure 1). Major referral indications Lung cancer The most common referral indication was known or suspected lung cancer -- 522 studies (20%). Our preliminary, prospective evaluation of the impact of PET scans on the management of 47 consecutive lung cancer patients found that, in over 60% of cases, management was significantly influenced by the scan result (Figure 2).16 In particular, in 32% of patients being considered for treatment with curative intent, management was changed to palliative therapy after documentation of previously unrecognised extrathoracic disease. In a more recent review limited to 140 consecutive patients being staged before definitive treatment of non-small-cell lung cancer, we found that PET changed treatment intent or modality in 47 patients (33%), altered delivery of the intended therapy in 39 patients (28%), and confirmed that the intended therapy was appropriate in only 39 patients (28%). In 15 patients (11%), an abnormality on PET, subsequently confirmed at follow-up, was ignored, with adverse outcome in all but two patients. Melanoma Assessing resectability of clinically localised metastatic disease in melanoma and staging of high-risk primary malignant melanoma have also been frequent indications -- 386 studies (14%) (possibly reflecting the presence of a dedicated melanoma unit at our institution). Based on data suggesting excellent accuracy of FDG PET for staging malignant melanoma,8 we have recently performed a comparison of this technique with high-dose gallium-67 (Ga-67) scanning, previously the standard functional imaging technique for high risk melanoma at our institution. This prospective comparison in 108 patients demonstrated concordance between these investigations in over 80% of cases.17 However, in a limited number of patients, absence of gallium avidity in metastatic melanoma deposits led to striking discordance between FDG PET and Ga-67 results (Figure 3). As FDG PET is a much more convenient study for patients, being completed in less than three hours (whereas Ga-67 requires scanning up to a week after injection), we have largely replaced Ga-67 scanning with PET for this indication at our institution. Head and neck cancer After surgery or radiotherapy, normal tissue planes can be scarred and disrupted. This complicates structural imaging or clinical examination for evaluation of residual or recurrent head and neck cancer. Thus, restaging was the most frequent indication for PET among the 318 studies (13%) in this subgroup. A preliminary review of our experience with FDG PET in 72 patients with head and neck cancer showed a positive predictive accuracy of 92% and a negative predictive accuracy of 100% for restaging.18Gastrointestinal malignancy Referrals of patients with gastrointestinal malignancy (251 studies --10%) have mainly been after primary management. Confirmation of resectability of apparently localised metastatic disease or suitability for local radiotherapy have been the major clinical indications. In a preliminary review of our experience in 41 patients,19 PET altered clinical management in 21 patients (52%), including 14 patients whose management was converted from aggressive locoregional therapy to palliative treatment based on demonstration of previously occult metastases (Figure 4). Breast cancer Evaluation of suspected recurrent or residual disease after treatment of breast cancer (190 studies -- 8%) has been the most common reason for referral of patients with breast cancer. Epilepsy Of the non-oncological indications, localisation of epileptogenic foci of complex partial seizures (88 studies -- 4%) was the most common reason for FDG PET studies. A recent review of our experience in epilepsy involving 52 patients demonstrated a sensitivity for localisation of a seizure focus of 83% versus only 49% by volumetric magnetic resonance imaging (MRI) in the same patient cohort.20 Of 20 patients with localising PET studies who have undergone surgery, 18 are currently seizure free and the other two have had a single seizure associated with drug withdrawal (unpublished data). Providing cost-effective PET in oncology Cost-effectiveness Despite an increasing body of evidence supporting the accuracy of FDG PET in oncology,5-7,9-15,21 its high cost and limited cost-effectiveness data have militated against funding for routine clinical use. In the United States, FDG PET scanning has been shown to be a cost-effective alternative to conventional diagnostic methods of assessing solitary pulmonary nodules22 and staging non-small-cell lung cancer,23 and now attracts reimbursement for these indications. US government funding of PET scans has recently been extended (on the basis of as yet unpublished cost-effectiveness analyses) to evaluation of suspected recurrent colorectal cancer and staging of melanoma and lymphoma (in place of high-dose gallium-67 scanning). In the United Kingdom, because of a reduction in surgical procedures, cost-effectiveness of PET for lung cancer staging has been reported.24 Our own preliminary data suggest a significant management impact of PET on lung cancer.16 Cost-benefit analyses to justify the use of FDG PET have shown significant savings even when based on costs derived from conventional PET facilities (quoted at US$1200, which includes technical and reporting costs).23 The ultimate cost of clinical PET scans depends on throughput of patients, availability and cost of radiopharmaceutical supplies, and the case mix of PET studies. Further evolution of lower-cost positron imaging devices and the development of production and distribution facilities to supply FDG to sites remote from a cyclotron have the potential to further reduce costs. If the cost of PET scans becomes more competitive, the merit of funding of PET for clinical use could be argued not on the basis of cost, but on its proven diagnostic and prognostic accuracy compared with standard investigations. A clinical service model As clinical service provision has been the major focus at our facility, our equipment and staffing reflect this orientation. Most other PET centres have focused on performing basic research as well as clinical studies. The capital and human establishment costs needed to perform the complex investigative studies that advance and validate PET technology increase the overall operational costs of such centres. The PET scanner at Peter McCallum Cancer Institute (GE Quest-300H, UGM Medical Systems Inc, Philadelphia, Pennsylvania, USA) uses scintillation crystals similar to those used in standard nuclear medicine gamma cameras. This significantly reduces the purchase price compared with conventional PET scanners. However, the documented spatial resolution and sensitivity are similar to current generation three-dimensional PET scanners.25 The larger axial field-of-view (25 cm v 16 cm) allows higher patient throughput. For example, whole-body imaging studies can be completed in less than an hour. The scanner characteristics limit administered radioacitivity to around 111 MBq (3 mCi) of F-18 FDG, compared with the typical dose of 300-555 MBq (8-15 mCi) with conventional PET scanners. This reduces operating costs, but limits the potential use of more short-lived PET tracers. Unlike amortisation costs, which fall, radioisotope costs increase as the number of patients studied per day increases. Because of radioactive decay, patients studied late in the day require far more isotope to be dispensed at the time of production. Decay also occurs during transport, and therefore proximity of the end-user to the cyclotron also influences daily isotope requirements and costs. A more sensitive scanner has particular advantages when used at a site remote from the production cyclotron. We believe that the relatively low start-up costs, high throughput and reduced operating expenses enable our facility to offer clinical PET studies at a cost that is significantly less than that generally quoted in the literature. Even with the lower cost of our model of practice, PET is likely to remain more expensive than other tomographic diagnostic procedures commonly used in cancer staging and therapeutic monitoring. However, the relatively poor diagnostic accuracy of these tests, when used alone, means that multiple investigations are often used or tests are supplemented by invasive staging procedures, making overall costs considerably higher. The advantages to patient quality of life of more accurate staging, particularly that which spares futile surgical intervention or reduces patient anxiety by timely assessment of therapeutic response, although more difficult to express in economic terms, can not be underestimated. Conclusion PET scanning has been available at our institution for three years. During this time it has been readily adopted by clinicians for planning of cancer management and for therapeutic monitoring. The high proportion of referrals from outside our institution suggests that there is growing awareness and high clinical acceptance of this technology among the medical community. Our own preliminary data support its utility in a wide range of oncological settings. More detailed prospective evaluation of the diagnostic accuracy and impact of PET in our institution is in progress and will help to further define the role of F-18 FDG PET in clinical oncology. By reducing scanning costs, the model of practice proposed offers the potential for PET to be become more widely available to the Australian community as a clinical rather than a research investigation. Acknowledgements Thanks to the staff of the cyclotron facilities at the Austin and Repatriation Medical Centre and the National Medical Cyclotron for providing timely supply of isotopes for clinical studies. We also thank the staff of our Department of Nuclear Medicine for taking on significantly increased work-loads with only a minimal increase in staffing levels, and Dr John Morris, the Chief Executive Officer of Peter McCallum Cancer Institute, for his ongoing support of the PET Program. References Tillisch J, Brunken R, Marshall R, et al. Reversibility of cardiac wall-motion abnormalities predicted by positron tomography. N Engl J Med 1986; 314: 884-888. Engel J, Henry TR, Risinger MW, et al. Presurgical evaluation for partial epilepsy: relative contributions of chronic depth-electrode recordings versus FDG-PET and scalp-sphenoidal ictal EEG. Neurology 1990; 40: 1670-1677. Rigo P, Paulus P, Kaschten BJ, et al. Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose. Eur J Nucl Med 1996; 23: 1641-1674. Price P, Jones T. Can positron emission tomography (PET) be used to detect subclinical response to cancer therapy? Eur J Cancer 1995; 31A: 1924-1927. Valk P, Pounds TR, Hopkins DM, et al. Staging non-small cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 1995; 60: 1573-1582. Coleman RE. PET in lung cancer. J Nucl Med 1999; 40: 814-820. Steinert HC, Hauser M, Allemann F, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node sampling. Radiology 1997; 202: 441-446. Steinert HC, Huch BÖni RA, Buck A, et al. Malignant melanoma: staging with whole-body positron emission tomography and 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1995; 195: 705-709. Delbeke D. Oncological application of FDG PET imaging; brain tumors, colorectal cancer, lymphoma and melanoma. J Nucl Med 1999; 40: 591-603. Benchaou M, Lehman W, Slosman DO, et al. The role of FDG-PET in the preoperative assessment of N-staging in head and neck cancer. Acta Otolaryngol 1996; 116: 332-335. Newman JS, Francis IR, Kaminski MS, Wahl RL. Imaging of lymphoma with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose: correlation with CT. Radiology 1994; 190: 111-116. Hoh CK, Glaspy J, Rosen P, et al. Whole-body FDG-PET imaging for staging of Hodgkin's disease and lymphoma. J Nucl Med 1997; 38: 343-348. Tse NY, Hoh CK, Hawkins RA, et al. The application of positron emission tomographic imaging with fluorodeoxyglucose to the evaluation of breast disease. Ann Surg 1992; 216: 27-34. Utech CI, Young CS, Winter PF. Prospective evaluation of fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer for staging of the axilla related to surgery and immunocytochemistry. Eur J Nucl Med 1996; 23: 1588-1593. Avril N, Bense S, Ziegler SI, et al. Breast imaging with fluorine-18-FDG PET: quantitative image analysis. J Nucl Med 1997; 38: 1186-1191. Kalff V, Hicks RJ, MacManus M, et al. The clinical impact of PET scanning in patients with lung cancer: a prospective study [Abstract]. J Nucl Med 1998; 39: 249. Hicks RJ, Kalff V, Binns DS, et al. Are high dose Ga-67 scans as good as FDG PET in staging melanoma? [Abstract] J Nucl Med 1998; 39: 11. Porceddu S, Hicks RJ, Rischin D, Peters L. Impact of PET on head and neck cancer. Proceedings of the 49th Annual Scientific Meeting of the Royal Australasian College of Radiology, 1998 Oct; Brisbane, Australia. [Abstract]: 290-291. Kalff V, Binns DS, Fawcett ME, Hicks RJ. Clinical impact of FDG PET scanning in colon cancer: a prospective study. Nucl Med Commun 1999; 20: 381. Murphy M, O'Brien TJ, Hicks RJ, et al. Experience of a 3-D, large-field-of-view PET scanner for the localisation of partial epilepsy. Annual Meeting of the American Epilepsy Society, 1999. Epilepsia (Suppl). In press. Strauss LG, Conti PS. The applications of PET in oncology. J Nucl Med 1991; 32: 623-648. Dewan NA, Reeb SD, Gupta N, et al. PET-FDG imaging and transthoracic needle lung aspiration biopsy in evaluation of pulmonary lesions: a comparative risk- benefit analysis. Chest 1995; 108: 441-446. Gambhir SS, Hoh CK, Phelps ME, et al. Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med 1996; 37: 1428-1436. Lewis P, Griffin S, Marsden P, et al. Whole body 18F-fluorodeoxyglucose positron emission tomography in preoperative evaluation of lung cancer. Lancet 1994; 344: 1265-1266. Karp JS, Muehllehner G, Mankoff DA, et al. Continuous-slice PENN-PET: a positron tomograph with volume imaging capability. J Nucl Med 1990; 31: 617-627. (Received 1 Jul, accepted 5 Oct, 1999) Authors' details The Peter MacCallum Cancer Institute, Melbourne, VIC. Rodney J Hicks, MD, FRACP, Director of Diagnostic Imaging. David S Binns, DipAppSci, ANMT, Chief Nuclear Medicine Technologist. Meagan E Fawcett, BAppSci, ANMT, Nuclear Medicine Technologist. Robert E Ware, MB BS, FCP(South Africa), Honorary Physician in Nuclear Medicine; currently, Director, Hobart Isotope Imaging, Hobart, TAS. Victor Kalff, MB BS, FRACP, Honorary Physician in Nuclear Medicine; currently, Deputy Director, Alfred Hospital, Melbourne, VIC. Allan F McKenzie, MB BS, FRACR, Director of Radiology. John R Zalcberg, PhD, FRACP, Professor, and Director of Medical Oncology. Lester J Peters, MD, FRACR, Professor, and Director of Radiation Oncology. Reprints: Dr R J Hicks, Director of Diagnostic Imaging, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett Street, Melbourne, VIC 3000. rhicksATpetermac.unimelb.edu.au The primary referral diagnosis was that prospectively assigned at the time of the PET study. Oncological indications were grouped by system (eg, "lung cancer" primarily comprised patients with non-small-cell tumours, but also included small-cell lung cancer and solitary pulmonary nodule). All imaging performed on a given day was counted as a single study. Almost all oncology patients had screening of areas remote from the known or suspected site of the primary tumour. The referral indication was known or suspected cancer in 2390/2500 cases (95.6%); 1881 individual patients had scans, with 619 follow-up studies in 379 patients for therapeutic monitoring or restaging after treatment. More than a third of our referrals were from clinicians without formal affiliation with our institution, including referrals from all States and Territories. The main referral indications at our facility reflect those cancers which have been shown to be accurately evaluated by PET - including lung cancer,5-7 melanoma,8,9 head and neck cancer,10 colorectal cancer,9 lymphoma,9,11,12 and breast cancer.13-15Back to text Figure 2. Non-small-cell lung cancer was diagnosed at bronchoscopy. A computed tomography scan was equivocal for mediastinal disease. FDG PET scanning of the thorax and abdomen was performed to assess suitability for surgical resection. The primary tumour (large arrows) and mediastinal nodal metastasis (small arrows) are clearly identified in transaxial (upper panel), sagittal (middle panel) and coronal (lower panel) projections. The patient was offered chemoradiotherapy rather than surgery. Back to text Figure 3: After resection of a melanoma of the left cheek, a palpable lymph node was shown (by fine-needle aspiration biopsy) to be a metastasis. A high-dose gallium-67 scan (left panel), which included tomographic imaging, did not demonstrate significant abnormality, so radical neck dissection was considered. Whole body FDG PET scanning (right panel) demonstrated disseminated metastases (arrows). The patient was spared unnecessary neck dissection and offered systemic therapy. Back to text Figure 4. After resection of a Duke C rectal carcinoma, this patient had rising carcinoembryonic antigen (CEA) levels and an apparently solitary hepatic metastasis (found at laparotomy - large arrow in left panel). At operation, a small bowel obstruction was thought to be related to postsurgical adhesions. FDG PET, performed to evaluate the patient's suitability for subsequent hepatic resection (right panel), demonstrated previously unrecognised widespread metastases (small arrows) and the patient was spared further futile surgery. Chemotherapy was commenced. Back to text

Rodney J Hicks · David S Binns · Meagan E Fawcett · Robert E Ware · Victor Kalff · Allan F McKenzie · John P Zalcberg · Lester J Peters

Editorial Sentinel node biopsy: evaluating a new technique Can we safely avoid axillary clearance in selected women with breast cancer? MJA 1999; 171: 452-453 Breast cancer is one of the most-researched areas of medicine, and best practice has evolved from well conceived and conducted randomised trials. For instance, we know that outcomes after breast-conserving surgery and mastectomy are equivalent, that adjuvant therapies improve survival, and that breast screening reduces mortality. Yet, many questions remain unanswered. In breast cancer, the status of the axillary nodes is one of the strongest prognostic indicators, and a major factor in determining adjuvant systemic therapy. Although the landmark National Surgical Adjuvant Breast Project (NSABP 04) study concluded that treatment of the axilla per se did not affect long-term survival,1 the issue of whether or not good local control (ie, radiotherapy or axillary clearance) affects survival is still debated,2,3 and the evidence to date suggests that at least Level 2 dissection -- 10 or more nodes -- is required for reliable assessment of axillary involvement.4 A proportion of women will experience complications after axillary dissection, including shoulder dysfunction, paraesthesiae and chronic lymphoedema.5 The question then arises: can we avoid axillary clearance in selected patients -- for example, by the technique of axillary node biopsy? This technique is based on the assumption that the status of the first node in the draining basin of the primary tumour is an accurate indicator of the overall status of that field of drainage; with a tumour-free sentinel node, axillary dissection may be unnecessary. Now that screening and evidence-based improvements to treatment are starting to have an impact on survival, we need to be wary of replacing well established methods with new techniques that have not been rigorously evaluated. Can sentinel node biopsy be implemented safely, with real long term benefits for our patients? In this issue of the Journal , Kollias and colleagues report their results with the sentinel node biopsy technique,6 which compare favourably with other international series. Sentinel nodes were identified successfully in 95 of the 117 women by a combination of three techniques -- lymphoscintigraphy, blue dye and a hand-held gamma probe (the latter two for intraoperative identification). Lymphoscintigraphy is an important prelude to sentinel node biopsy, but in the series of Kollias et al it successfully mapped the sentinel node in only 63.2% of cases. However, the authors point out that they were able to improve the accuracy by increasing the injection volume. The skill and persistence of the nuclear physician are key factors in obtaining optimal lymphoscintigraphy. In Australia, we are fortunate to have a radiopharmaceutical (99mTc-labelled antimony sulfide colloid) that is superior to those available in other countries. This means that we may produce more accurate maps of lymphatic drainage, and thereby identify sentinel nodes more often. Research reported from the Royal Prince Alfred Hospital in Sydney has shown that drainage patterns from individual tumours can be quite unexpected.7 This new area of study means that we will have to re-evaluate the whole notion that "skip metastases" occur, and their significance in determining overall prognosis.8 If a decision on whether to dissect the axilla had been based on a confirmed tumour-negative sentinel node, then 66 of the 117 women in the study of Kollias and colleagues would have been spared axillary dissection, although in two women this would have been a false negative diagnosis (two of the 31 women with nodal involvement had sentinel nodes negative for tumour). This rate (6.5%) is comparable with those in other series.9,10 Although we should be concerned about the false negative rate of sentinel node biopsy, we should also recognise that some occult metastases are not detected in standard haematoxylin-eosin histopathological sections. With standard staining methods, the false negative rate in a series of patients reported from St Vincent's Hospital in Melbourne was 12%; in that series, antimucin monoclonal antibodies showed micrometastatic deposits in 41 of 343 patients previously classified as having node-negative breast cancer by haematoxylin-eosin staining.11 False negative assessments are inevitable when lymph nodes are sampled, but the more detailed examination of one or two "sentinel" nodes may prove more beneficial than the standard examination of many nodes. The detection of micrometastatic deposits introduces a new area of uncertainty requiring further study -- we have yet to determine their significance. How do they affect prognosis and how should we treat them? Ongoing evaluation of locoregional recurrence and distant disease is essential. At first glance, sentinel node biopsy appears invitingly easy, but success in completing the sometimes technically difficult procedures involved will define the oncological relevance of the technique. Simply removing a "hot" or "blue" node is not enough -- we have to reappraise our indications for treating the internal mammary nodes and the supraclavicular nodes, as well as those in the axilla, as nodes from more than one site may be involved. It is equally important that women with breast cancer be managed in consultation with oncologists: women treated in a multidisciplinary setting tend to have better outcomes.12 While Kollias et al conclude that sentinel node biopsy is an accurate method of assessing axillary lymph node status, the accuracy has varied in other series. Reported detection rates range from 66% to 100% and false negative rates from zero to 17%.13 Why is there such a discrepancy? A possible explanation is the different techniques used in individual series. Some surgeons used only one method of localisation; others used different combinations of the three techniques -- different dyes, different radiopharmaceuticals, different times between injection and surgery, different methods of injection, and even different criteria by which sentinel nodes are searched for and removed. In Australia, we have a window of opportunity to work towards a standardised approach to sentinel node biopsy, using agreed protocols and prospective and uniform data collection. Kollias and colleagues, and other representatives from the major breast units and the Section of Breast Surgery of the Royal Australasian College of Surgeons, are working together and have proposed an Australasian prospective randomised trial with the capacity to involve all surgeons who are interested in breast cancer management. New techniques require proper evaluation. As a group, surgeons have been quick to adopt new procedures before scientific validation.14 In addition, consumer pressures, and sometimes market pressures, are at work. For comparison, consider laparoscopic cholecystectomy, which has now gained widespread approval. The learning curve was steep -- the early reports of this technique were full of enthusiasm and the procedure was adopted rapidly. There is no doubt that, in those early days, considerable morbidity for many patients could have been avoided with more caution and less haste.15 The technical aspects of these two quite different operations are not comparable; the parallel to be drawn relates to the way new procedures may be incorporated into, and perhaps finally adopted as, standard procedures. It therefore behoves us to ensure that, with any new procedure, consumers are not placed at increased risk, particularly if it is performed with limited expertise. Owen A Ung Clinical Services Director New South Wales Breast Cancer Institute, and Breast and Endocrine Surgeon Westmead Hospital, Sydney, NSW owenuATbci.org.au Neil R Wetzig Chairman, Section of Breast Surgery Royal Australasian College of Surgeons and Senior Surgeon Princess Alexandra Hospital, Brisbane, QLD Fisher B, Redmond C, Fisher ER, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med 1985; 312: 674-681. Harris JR, Osteen RT. Patients with early breast cancer benefit from effective axillary treatment. Breast Cancer Res Treat 1985; 5: 17-21. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997; 337: 949-955. Axelsson CK, Mouridsen HT, Zedeler K, on behalf of The Danish Breast Cancer Cooperative Group (DBCG). Axillary dissection of level I and II lymph nodes is important in breast cancer classification. Eur J Cancer 1992; 28A: 1415-1418. NHMRC National Breast Cancer Centre. Lymphoedema: prevalence, risk factors and management: a review of research. Sydney: NBCC, 1997. Kollias J, Gill PG, Chatterton BE, et al. Reliability of sentinel node status in predicting axillary lymph node involvement in breast cancer. Med J Aust 1999; 171: 461-465. Uren RF, Howman-Giles RB, Thompson JF, et al. Mammary lymphoscintigraphy in breast cancer. J Nucl Med 1995; 36: 1775-1780. Danforth DN, Findlay PA, McDonald HD, et al. Complete axillary lymph node dissection for stage I-II carcinoma of the breast. J Clin Oncol 1986; 4: 655-662. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994; 220: 391-398. Krag DN, Ashikaga T, Harlow SH, Weaver DL. Development of sentinal node targeting technique in breast cancer patients. Breast J 1998; 4: 67-74. Hainsworth PJ, Tjandra JJ, Stillwell RG, et al. Detection and significance of occult metastases in node-negative breast cancer. Br J Surg 1993; 80: 459-463. Sainsbury R, Haward B, Rider L, et al. Influence of clinical workload and patterns of treatment on survival from breast cancer. Lancet 1995; 345: 1265-1270. McIntosh SA, Purushotham AD. Lymphatic mapping and sentinel node biopsy in breast cancer. Br J Surg 1998; 85: 1347-1356. Solomon MJ, McLeod RS. Surgery and the randomised controlled trial: past, present and future. Med J Aust 1998; 169: 380-383. The Southern Surgeons Club. A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med 1991; 324: 1073-1078.

Research Reliability of sentinel node status in predicting axillary lymph node involvement in breast cancer James Kollias, P Grantley Gill, Barry E Chatterton, Vivian E Hall, Melissa A Bochner, Brendon J Coventry and Gelareh Farshid MJA 1999; 171: 461-465 For editorial comment, see Ung & Wetzig Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - More articles on Oncology Abstract Objectives: To assess the reliability of determining sentinel node status in staging regional lymph nodes in breast cancer. Design and setting: Prospective validation study in a major public teaching hospital, comparing histological sentinel node status with that of remaining axillary nodes. Patients: 117 women who underwent sentinel node biopsy and axillary dissection for primary breast cancer between 1995 and 1998. Main outcome measures: Intraoperative success rate in sentinel node identification; false negative rate; predictive value of negative sentinel node status; overall accuracy of sentinel node status. Results: The sentinel node was identified at operation in 95 patients (81.2%). Tumour involvement of the sentinel node was demonstrated in 29 of 31 women (93.5%; 95% CI, 79%-99%). Sixty-four of the 66 women in whom the sentinel node was negative for tumour showed no further involvement of remaining axillary nodes (standard haematoxylin-eosin histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 women in whom sentinel node status was compared with axillary node status was 97.9%. Conclusions: Histopathological examination of the sentinel node is an accurate method of assessing axillary lymph node status in primary breast cancer and is likely to be incorporated into future surgical management of women with primary breast cancer. Introduction Axillary lymph node status is the most important prognostic indicator in early breast cancer, and the detection of nodal metastases is a key factor in recommending adjuvant systemic therapy after surgery.1,2 Surgical removal and histopathological assessment of these nodes remains the only accurate way of determining their involvement with tumour. Axillary dissection also reduces the risk of regional recurrence of breast cancer in the axilla,3 as the risk is inversely related to the number of axillary nodes removed.4However, axillary lymph node dissection is not without morbidity: seroma formation, wound infection, damage to nerves, and reduced shoulder mobility. Of particular importance is lymphoedema, which occurs in 15% and 30% of women.5-8 As a consequence, other, less invasive methods of assessing axillary node status have been investigated (eg, mammography, ultrasound and colour doppler imaging, magnetic resonance imaging [MRI] and positron emission tomography [PET] scanning), but have yet to achieve the accuracy of surgical staging. Axillary node sampling -- removal of a small number of Level 1 nodes (those below the lower border of the pectoralis minor muscle) -- is associated with fewer complications, and has been proposed as an alternative to complete axillary dissection for staging of the axilla.9,10 However, its efficacy has been questioned.11 With the advent of population-based mammographic screening programs, there has been a dramatic decrease in tumour size and lymph node involvement in women diagnosed with early breast cancer.12,13 Thus, an increasing proportion of women will undergo axillary dissection only to find that their lymph glands are free of disease. Ideally, there should be a method of providing accurate assessment of axillary lymph node status without the need for axillary dissection. The sentinel lymph node (the first draining node within a lymph node basin) is the first to receive lymphatic drainage from a tumour site. Selective biopsy of this node allows the detection of metastases in clinically normal nodes with a low false negative rate, and has been used in patients with operable breast cancer by several groups.14-19 Their findings indicate that the status of the sentinel node(s) can accurately predict that of the fully dissected axilla. We report our experience of lymphoscintigraphy, intraoperative sentinel node mapping and sentinel node biopsy in 117 women with primary operable breast cancer. Our aims were: To assess the success rate of lymphoscintigraphy and intraoperative lymph node mapping in identifying the sentinel node; and To assess the accuracy of sentinel node biopsy in staging the axillary nodes. Methods Patients A consecutive series of 117 women treated for primary breast cancer at the Royal Adelaide Hospital Breast Unit between June 1995 and August 1998 entered a prospective evaluation of the technique of sentinel lymph node biopsy in breast cancer. Ethical approval for the study was provided by the Human Ethics Committee of the Royal Adelaide Hospital. All women gave written informed consent to participate in the study. Eligibility criteria were: Operable primary breast cancer (tumour, < 5 cm in diameter), detected clinically and by imaging, and confirmed by cytology, core biopsy or open biopsy; Clinically impalpable axillary lymph nodes; and The usual surgical indications for axillary dissection (ie, invasive, operable cancer). Patients were excluded if their condition did not fulfil these criteria; if they were pregnant or currently breastfeeding; if there was a high clinical suspicion or preoperative verification of axillary nodal involvement; or if they had metastatic breast carcinoma or a preoperative diagnosis of ductal carcinoma-in-situ. The women's ages ranged from 31 to 82 years (median, 60 years). Their clinical characteristics are summarised in Table 1. During the period of study, no eligible women refused entry to the study. Isotope injection technique The radiopharmaceutical used was 99mTc-labelled antimony sulfide colloid ("Lymph-Flo", Royal Adelaide Hospital Radiopharmacy). The colloid underwent filtration through a 0.2-µ sterile filter, ensuring more than 80% of the filtered particles were smaller than 20 nm. A 32-mm, 25-gauge needle was used to inject 40 MBq of tracer to four sites surrounding the palpable margin of the breast lesion. If the lesion was not palpable, ultrasound localisation was performed, and the injection was given in a similar manner under ultrasound guidance. In the initial stages of the study, 0.5 mL of tracer was injected in each of 82 patients. For the remaining 35 women, the injected volume was increased to 4 mL in four divided doses. In these latter women, the injection site was lightly massaged, and they were instructed to move their arms to encourage lymphatic movement. All radioisotope injections were given on the morning of the day of surgery. Lymphoscintigraphy and lymph node mapping After injection, serial anterior and appropriate lateral images were obtained with a large-field-of-view gamma camera (GE XRT, General Electric) at about 15-minute intervals until the initial draining node (or nodes) was visualised (Figure 1). The surface projection of the sentinel node was then marked on the skin with a radioactive marker. Orthogonal projections were made by the established technique of "triangulation"; the marks were joined by a straight line to indicate the base of a right-angled triangle with the node at the apex. Body outline was marked with a radioactive marker, or a transmission image was performed by holding a "flood" source behind the patient. The intraoperative probe (RMD CTC 4 with audible guidance system, Gammasonics, Melbourne) was calibrated in the Nuclear Medicine Department to the counts detected at the skin surface. Surgical technique After completion of lymphoscintigraphy and sentinel node mapping, the patient and hand-held gamma probe were transferred to the operating theatre. In 66 patients, 1-2 mL of 2.5% Patent Blue V dye (Guerbet Laboratories, France; distributed by Fauldings Australia, Adelaide) was injected into the breast parenchyma or subdermal fat overlying the tumour to facilitate intraoperative identification of the sentinel node. Blue dye alone was used in 19 patients before a gamma probe was available. At operation, a 2-cm transverse axillary incision was made in accordance with the planned axillary lymph node dissection, but taking into account the preoperative skin markings indicating the location of the sentinel node at lymphoscintigraphy. An attempt was made to identify the node in vivo before commencement of axillary dissection. The node was identified by its blue colour (if dye was used) and/or by the hand-held gamma probe (in a sterile sheath). The probe enabled detection of individual nodes with radioactivity levels significantly greater than those of the axillary fat (Figure 2). Sometimes more than one sentinel node was identified. If both dye and radioisotope were used for lymphatic mapping, the blue node corresponded to the most radioactive node. Once the sentinel node was removed, its activity was reassessed ex vivo and it was sent for histological examination separately from the main axillary nodal specimen. The axillary fat was then examined with the gamma probe in vivo to exclude any residual activity suggesting further sentinel nodes. The axillary skin incision was then lengthened and a level I and II axillary lymph node dissection was performed. The resected axillary tissue was examined ex vivo using the probe to identify any further radioactive or blue lymph nodes not identified during in-vivo examination. Histopathological examination All specimens were examined by duty histopathologists at the Institute of Medical and Veterinary Science. The histological tumour features were classified according to tumour size and grade,20 and presence or absence of vascular invasion.21 Generally, sentinel nodes were submitted in their entirety for histological evaluation. Those larger than 1.5 cm were sliced before paraffin embedding. Each node was placed in an individual cassette. At least one section of each node was stained with haematoxylin-eosin (H&E) and examined with light microscopy. Immunohistochemical analysis (antikeratin antibody CAM 5.2, Becton Dickinson) was performed in H&E-stained sections suspected of having metastatic tumour deposits. The axillary fat was fixed in formalin and the nodes were later isolated from the fat after clearance in Carnoy's solution. Each node was placed in an individual cassette and larger nodes were sliced before being embedded in paraffin. At least one H&E-stained section of each node was examined. Statistical analysis A false negative sentinel node was defined as an excised sentinel lymph node which contained no microscopically detectable tumour, but which was associated with at least one tumour-positive node in the remaining resected axillary tissue. The false negative rate and the predictive value of negative sentinel node status were calculated together with 95% confidence intervals. The kappa (κ) statistic for paired data was used to assess the level of agreement between sentinel node status and axillary node status.22 A score of -1 indicates perfect disagreement and + 1 indicates perfect agreement. The corresponding z and P values were calculated. Univariate analysis was used to assess clinical and histological factors that predicted intraoperative sentinel node localisation. Fisher's exact and χ2 tests were used for other analyses between groups. Results Lymphoscintigraphy The sentinel node was identified on preoperative lymphoscintigraphy in 74 of 117 women (63.2%). One sentinel node was identified in 52 women, two were identified in 20 women, and in two further women three and four sentinel nodes were identified, respectively. The sentinel node was identified outside the lower axilla in nine patients (Table 2). A significant increase in sentinel node identification at lymphoscintigraphy was noted after the injection of larger isotope volumes into the breast (77% v 57%; χ2 = 4.15; P = 0.04), while rates of intraoperative detection of the sentinel node also increased (91% v 76%; χ2 = 3.4; P = 0.06). Intraoperative sentinel node identification The sentinel node was identified in 95 patients (81.2%) at operation. In 66 women, one sentinel node was identified, two were identified in 20 women, three in eight women, and in one four sentinel nodes were identified. The sentinel node was identified in 35 of the 51 women in whom radioisotope alone was used (68.6%), compared with 18 of 19 women in whom blue dye alone was used (94.7%) and 42 of 47 women in whom both isotope and blue dye were used (89.4%) (χ2 = 9.6; P = 0.008). Of the clinical and histological factors assessed for predicting intraoperative sentinel node identification, only a positive preoperative lymphoscintigram was significant (χ2 = 28.7; P < 0.001) (Table 3). Predictive value of sentinel node(s) In 95 patients in whom the sentinel node was identified, 31 had metastatic tumour involvement of axillary nodes (32.6%). Tumour involvement of the sentinel node was demonstrated in 29 of these 31 women (93.5%; 95% CI, 79%-99%), giving a false negative rate of 6.5%. The sentinel node was the only positive node in 13 of 31 women (41.9%). Of 66 women with a negative sentinel node, 64 had no tumour involvement in the remainder of the axillary nodes (by standard H&E histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 patients in whom sentinel node status was compared with axillary node status was 97.9% (κ, 0.95; z = 9.3; P < 0.001) (Table 4). Of the 22 women in whom the sentinel node was not identified at operation, six had nodal metastases on histological examination of the dissected axillary nodes. Discussion The concept of the sentinel lymph node is based on the premise that the first lymph node to receive lymphatic drainage from a tumour site should be the first site of lymphatic spread; that "skip metastases" do not occur; and that the absence of tumour metastases in the sentinel node implies the absence of lymph node metastases in the entire lymphatic basin. This concept was first described in penile carcinoma in 197723 and was later studied in patients with cutaneous melanoma.24 Previous detailed pathological studies of axillary nodes in women with breast cancer have demonstrated a skip metastasis rate of less than 5%.25,26Our results confirm that the status of the sentinel lymph node(s) predicts the overall axillary lymph node status with a high degree of accuracy, and can thus be used to limit the morbidity associated with axillary surgery. More importantly, the predictive value of a tumour-free sentinel node was 97%. As such, women identified with a sentinel node free of metastatic tumour can be reassured that further axillary lymph node involvement is highly unlikely. Other studies of sentinel node biopsy in breast cancer (using blue dye and radioactive isotope techniques) have shown sentinel node status to accurately determine axillary lymph node status in more than 95% of women.14-19 We still need to deal with the problem that 3% of patients exhibited tumour-positive axillary nodes when the biopsied sentinel node was negative. The optimal method of pathological assessment of the sentinel node remains unresolved and was not addressed in our study. This issue was discussed at the Adelaide Workshop on Sentinel Node Biopsy in Breast Cancer27 and is the subject of further studies by one of us (G F). Giuliano et al28 have found that immunohistochemical studies of sentinel nodes showed micrometastases in an additional 11% of women whose sentinel node was tumour negative on light microscopy. However, similar assessment of two women with false negative results in our study did not reveal metastases. The implications of micrometastases detected by sensitive immunohistochemical and polymerase chain reaction (PCR) techniques for multidisciplinary care are unknown. They are currently being investigated in trials in the United States (Merrick Ross, Associate Professor of Surgical Oncology, M D Anderson Hospital, Texas, USA, personal communication). Until the answers to this question are available, a large UK trial (ALMANAC) is assessing sentinel node status by conventional microscopy (R Mansell, Professor of Surgery, Cardiff University, UK, personal communication), as this is the current method on which treatment planning is based. These uncertainties emphasise the need for Australian studies to incorporate detailed protocols for pathology assessment of the sentinel node. The prognostic implications of a false negative sentinel node are uncertain, but should be compared with the considerable physical morbidity associated with axillary dissection in lymph node negative women. There is a definite error rate in routine pathological assessment of axillary dissection specimens which may underestimate metastatic disease by 11%-30%,27,29 while unselective sampling of the axilla fails to remove involved nodes in many women.11 The false negative rate must ultimately be minimised by maximal detection of the sentinel node by scintigraphy, careful operative technique and optimal pathological assessment, which requires an experienced multidisciplinary team. The concomitant intraoperative use of both blue dye and radionuclide methods for lymphatic mapping was particularly useful for sentinel node biopsy. Preoperative lymphoscintigraphy permits identification of the sentinel node and subsequent planning of the site of skin incision. Several radiolabelled colloids are currently in use around the world, but the recent workshop in Adelaide27 identified antimony colloids as having excellent properties for lymphoscintigraphy. This is the only agent available for this purpose in Australia and is able to visualise sentinel nodes in the internal mammary chain as well as in the axillary node group. The blue dye technique facilitated visualisation of the sentinel node at the time of surgery and was supplemented by the use of an intraoperative gamma probe. In all patients in whom both blue dye and radionuclide were used, the blue node corresponded to the "hot" node previously identified on lymphoscintigraphy and identified intraoperatively with the hand-held gamma probe. Furthermore, the identification of a sentinel node at preoperative lymphoscintigraphy was the only factor significantly associated with the intraoperative identification of the sentinel node. Lymphoscintigraphy also demonstrates the number and location of potential sentinel nodes requiring biopsy. The initial rate of preoperative identification of the sentinel node by lymphoscintigraphy in our series was lower than that in published reports. However, this was overcome by increasing the volume of the isotope injection and presumably increasing tissue oncotic pressure, lymphatic uptake and drainage. The importance of isotope volume in achieving successful scintigraphic identification of the sentinel node has also been suggested by others.30 Sentinel lymph node mapping and biopsy are likely to be incorporated into clinical practice, provided they can be successfully performed in most patients, and it can be shown that women with negative sentinel nodes who undergo no further treatment to the axilla are not adversely compromised in terms of disease-free and overall survival. This will be best established by randomised controlled studies comparing sentinel node biopsy with standard axillary surgical management. In addition, these studies should address the implied assumption of lower short and long term morbidity associated with this procedure, the optimal methods of pathological assessment, and allow analysis and comparison with clinicopathological variables in predicting sentinel node status. Studies are currently being undertaken in Europe, the United Kingdom and the United States and it is hoped that Australian women can soon participate in similar trials in Australia. References Carter CL, Allen C, Henson DE. Relation of tumour size, lymph nodes status and survival in 24,740 breast cancer cases. Cancer 1989; 63: 181-187. Fisher ER, Anderson S, Redmond C, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project Protocol B-06: 10 year pathological and clinical prognostic discriminants. Cancer 1993; 71: 2507-2514. Fisher D, Woolmark N, Bauer M, et al. The accuracy of clinical nodes staging and of limited axillary dissection as a determinant of histological nodal status in carcinoma of the breast. Surg Gynecol Obstet 1991; 152: 765-772. Axellsson CK, Mouridsen HT, Zedeler K. Axillary dissection of Level I and II lymph nodes is important in breast cancer classification: The Danish Breast Cancer Cooperative Group (DBCG). Eur J Cancer 1992; 28: 1415-1418. Kissin MW, Querci-Della-Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986; 73: 580-584. Aitken RJ, Gayes MN, Rodger A, et al. Arm morbidity within a trial of mastectomy and either node sample with selective radiotherapy or axillary clearance. Br J Surg 1989; 76: 568-571. Larson D, Weinstein M, Goldburg I, et al. Oedema of the arm as a function of the extent of axillary surgery in patients with Stage 1-2 carcinoma of the breast treated with primary radiotherapy. Int J Radiat Oncol Biol Phys 1986; 12: 1575-1582. Liljegren G, Holmburg L. Arm morbidity after sector resection and axillary dissection with or without postoperative radiotherapy in breast cancer. Stage 1: Results from a randomised trial. Uppsala Orebro Breast Cancer Study Group. Eur J Cancer 1997; 33: 193-199. Steel RJC, Forrest APM, Gibson T, et al. The efficacy of lower axillary sampling in obtaining lymph node status in breast cancer: a controlled randomised trial. Br J Surg 1985; 72: 368-369. Dixon JM, Dillon P, Anderson TJ, Chetty U. Axillary node sampling in breast cancer: an assessment of its efficacy. Breast 1998; 7: 206-208. Kissin MW, Thompson PH, Price AB, et al. The inadequacy of axillary sampling in breast cancer. Lancet 1982; 1: 1210-1212. Tabar L, Fagerberg G, Duffy SW, et al. Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am 1992; 30: 187-210. Cady B, Stone MD, Schuler JG, et al. The new era in breast cancer: invasion, size and lymph node involvement dramatically decreased as a result of mammographic screening. Arch Surg 1996; 131: 301-308. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy in breast cancer. Ann Surg 1994; 220: 391-401. Albertini JJ, Lyman GH, Cox C, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA 1996; 276: 1818-1822. Veronesi U, Paganelli G, Galimberti V, et al. Sentinel node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet 1997; 349: 1864-1867. Borgstein PJ, Pijpers R, Comans EF, et al. Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg 1998; 186: 275-283. Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998; 227: 645-653. O'Hea BJ, Hill ADK, El-Shirbiny AM, et al. Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center. J Am Coll Surg 1998; 186: 423-427. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19: 403-410. Pinder SE, Ellis IO, Galea M, et al. Pathological prognostic factors in breast cancer. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 1994; 24: 41-47. Fliess JL. Statistical methods for rates and proportions. 2nd edition. New York, NY: John Wiley and Sons, 1981. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977; 39: 456-466. Morton DL, Wen D-R, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 392-399. Berg JW. The significance of axillary node levels in the study of breast cancer. Cancer 1955; 8: 776-778. Veronesi U, Rilke F, Luimi A, et al. Distribution of axillary node metastases by level of invasion: an analysis of 539 cases. Cancer 1987; 59: 682-687. Kollias J, Gill PG, Chatterton B, et al. Sentinel node biopsy in breast cancer: recommendations for surgeons, pathologists, nuclear physicians and radiologists in Australia and New Zealand. Aust N Z J Surg 1999. In press. Giuliano AE, Dale PS, Turner RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995; 222: 387-399. Hainsworth PJ, Tjandra JJ, Stillwell RG, et al. Detection and significance of occult metastases in node negative breast cancer. Br J Surg 1993; 80: 459-463. Krag DN, Ashikaga T, Harlow SH, Weaver DL. Development of sentinel node targeting technique in breast cancer patients. Breast J 1998; 4: 67-74. (Received 22 Apr, accepted 9 Sep, 1999) Authors' details Royal Adelaide Hospital and Women's Health Centre, Adelaide, SA. James Kollias, MB BS, FRACS, Staff Surgeon, Breast-Endocrine and Surgical Oncology Unit. P Grantley Gill, FRACS, MD, Head, Breast-Endocrine and Surgical Oncology Unit; and Associate Professor, University of Adelaide. Barry E Chatterton, MB BS, FRACP, Director, Department of Nuclear Medicine. Vivian E Hall, MB BS, FRACR, Radiologist, Department of Radiology. Melissa A Bochner, MB BS, FRACS, Senior Registrar, Breast-Endocrine and Surgical Oncology Unit. Brendon J Coventry, FRACS, PhD, Senior Surgeon, Breast-Endocrine and Surgical Oncology Unit; and Senior Lecturer, University of Adelaide. Department of Tissue Pathology, Institute of Medical and Veterinary Science, Adelaide, SA. Gelareh Farshid, MB BS, FRCPA, Senior Lecturer, University of Adelaide. Reprints will not be available from the authors. Correspondence: Associate Professor P G Gill, Breast-Endocrine Surgical Oncology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000. cbatesbrownswordATmedicine.adelaide.edu.au Back to textBack to textBack to textBack to text 3: Clinical and histological features predicting success in sentinel node identification at operationVariableNo. of womenSentinel node identified (%)χ2 (P)Age (years)< 503330 (91%)2.84> 508465 (77%)(0.09)Tumour site (quadrant)Upper/outer86 69 (80%)0.2Lower/inner31 26 (84%)(0.66)Tumour detectionScreening56 42 (75%)2.7Symptomatic61 53 (87%)(0.1)Previous core biopsyYes1210 (83%)0.04No10585 (79%)(0.84)Previous open biopsyYes11089 (81%)0.1No76 (86%)(0.75)Scintiscan resultPositive74 71 (96%)28.7Negative43 24 (56%)(< 0.001)OperationMastectomy31 24 (77%)1.23Wide local excision5547 (85%)(0.54)Localised wide local excision3124 (77%)Tumour size*< 2cm79 64 (81%)0.03≥ 2cm36 29 (81%)(0.95)Tumour grade*12721 (78%)2.425346 (87%)(0.31)33526 (74%)Lymphatic/vascular invasionNegative101 83 (82%)0.44Positive16 12 (75%)(0.5)Lymph node statusNegative80 64 (80%)0.2Positive37 31 (84%)(0.6) * Excludes two cases of ductal carcinoma-in-situ, diagnosed after excision. 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James Kollias · Barry E Chatterton · Vivian E Hall · Melissa A Bochner · Brendon J Coventry · Gelareh Farshid

Review Breast cancer screening and management A Patrick M Forrest and Elaine D C Anderson MJA 1999; 171: 479-484 Synopsis - Introduction - Why screen for breast cancer? - Evidence for screening - Screening programs - Breast self-examination - Familial breast cancer - Management of screen-detected breast cancer - The future -- specialised, multidisciplinary services - Acknowledgements - References - Authors' details - - More articles on Oncology Synopsis Mammographic screening to detect preclinical cancer was introduced when it was realised that once breast cancer became symptomatic it could not be cured regularly by local surgery, as early systemic dissemination had almost invariably occurred. Meta-analysis of randomised controlled trials of screened versus unscreened women has demonstrated a mortality benefit approaching 30% in screened women (> 50 years of age) seven to nine years from the start of the trials. The UK and Australian breast screening programs are compared. Differences in the design are largely a result of differences in the healthcare systems in the two countries. Breast self-examination, although still recommended by many Australian practitioners, is not an appropriate screening method, as it does not affect breast cancer death rates. About 5% of women have familial breast cancer (associated with mutations of BRCA1 or BRCA2). Women at high risk are screened at an earlier age and at more frequent intervals. Current best practice management of screen-detected breast cancer, including surgery, radiotherapy, assessment of the axilla, and systemic therapy, is summarised. Women with symptomatic breast disease ideally should be treated by a specialised multidisciplinary service, which can provide sophisticated diagnosis and treatment as well as supportive care. Introduction In 1987, the UK government initiated screening for breast cancer by a single medial-lateral oblique view of each breast every three years for all women aged 50-64 years.1 The breast screening program in Australia -- BreastScreen -- began in 1991 and provides two-view mammographic screening at two-year intervals, mainly for women aged 50-69 years.2 Why screen for breast cancer? Screening was introduced when long term follow-up studies showed that most women with symptomatic breast cancer could not be cured by local surgery.3,4 Breast cancer was not a slowly progressive, locoregional disease; early systemic dissemination with the formation of distant micrometastases was the rule. Proof of this has now come from unequivocal evidence that systemic treatment, either by anti-oestrogens or chemotherapy, significantly prolongs survival in women with symptomatic disease.5-7Mammographic screening can detect cancer of the breast in its preclinical phase (ie, before it is palpable). The success of screening depends in part on the size of the tumour and whether the cancer has spread to the axillary lymph nodes, but the tumour's biological aggressiveness also needs to be taken into account. The excision of small tumours which are markedly undifferentiated may save lives in the short term, but it is the detection of small tumours while still of favourable grade which is likely to confer the greatest long term benefit. Evidence for screening Evidence that mammographic screening reduces mortality comes from randomised trials comparing mortality from breast cancer of women invited to be screened with women without any intervention. Recent meta-analyses have demonstrated a mortality benefit approaching 30% in women over 50 years of age seven to nine years from the start of the trials.8,9 In the 70% of women who accepted the invitation, mortality reduction is obviously larger. The 14-year follow-up of one of these six randomised trials,10 initiated in Edinburgh in 1978 and including over 22 000 women, indicated a reduction in breast cancer deaths of 21% (relative risk [RR], 0.79; 95% CI, 0.60-1.02), which bordered on significance. As patients diagnosed with breast cancer after the conclusion of the trial (when both study and control groups were eligible for screening) could not have influenced the mortality rate, a further analysis was performed with patients censored 10 years after entry. The 29% mortality reduction was significant (RR, 0.71; 95% CI, 0.53-0.95), and this mortality advantage was no less in women 45-50 years of age than in older women.10 Screening programs In the NHS Breast Screening Programme in the United Kingdom, the need for quality at every stage of the screening process has been emphasised, and national coordinators and regional advisory committees publish annual reports which include regularly revised targets against which performance can be measured (Boxes 1 and 2).11Australia's program, BreastScreen, which began in 1991, has a different design and less standardisation than in the UK program, largely because Australian general practitioners and surgeons work as independent providers. Women aged 50-69 years are eligible for two-yearly screening, but younger women, 40-50 years, and those over 70 years are screened on request. Women in the target group are invited to take part by direct mailouts based on the electoral roll, and 1996-1997 compliance rates were 52.2%.2 Two-view mammography is used, and double reading of mammograms is mandatory. However, the experience of radiologists reading mammograms, the protocols for assessment of screen-detected lesions, and arrangements for surgical biopsies and their pathological interpretation vary greatly between clinics and between States and Territories. National evaluation is only now under way. Breast self-examination Breast self-examination (BSE) can detect symptomatic breast cancer at an earlier stage, but it does not appear to influence mortality. A recent American Cancer Society study compared 177 602 women who practised BSE during the preceding 13 years with 272 554 women who did not, and found similar breast cancer death rates in the two groups.12 The UK Trial of Early Detection of Breast Cancer (TEDBC)13 involved 300 000 women in eight health districts, two with mammographic screening centres, two where BSE was taught by trained nurses, and four where neither form of intervention was available. At 16 years the relative risk of death from breast cancer in women attending the two screening clinics was reduced by 27% (RR, 0.73; 95% CI, 0.63-0.84), but there was no risk reduction in the two BSE centres (RR, 0.99; 95% CI, 0.87-1.12). Three randomised trials to evaluate the effect of BSE on breast cancer mortality are under way in St Petersburg and Moscow,14 and Shanghai.15 Preliminary results of the Shanghai study, which included over 250 000 women, found a similar incidence and an identical number of breast cancer deaths among BSE subjects and controls.15 BSE has greatly increased biopsy rates, with the number of benign lesions detected in the BSE group being twice those of the controls.15 These findings indicate that women should be aware of their breasts as part of general body awareness and seek medical help when their breasts look or feel abnormal, but the promotion of regular BSE is not justified. Familial breast cancer Some 20% of women with breast cancer report a "family history", but only about 5% are truly familial cancers, with the proportion being greater in women under 45 years at diagnosis (Box 3). Management of screen-detected breast cancer A recent audit of 500 screen-detected invasive cancers treated in Scottish hospitals found that 75% were under 1 cm in size and 70% node negative.30 Mastectomy is not necessarily the best treatment for such cancers; some surgeons believe that local excision alone is appropriate. However, the results of five randomised trials show a high local relapse rate if radiotherapy is not also given (Box 4).31-35 After nine years of follow-up in the US National Surgical Adjuvant Breast Project B-06 (NSABP B-06) trial, the relapse rate reached 43%.36 As these trials included tumours of 2.5-4 cm in size, the need for radiotherapy in small (< 1 cm) tumours of low grade and special histological type is unknown. Some surgeons believe that if tamoxifen is given after local excision radiotherapy can be avoided. The Scottish Conservation Trial, in which all 585 patients were prescribed adjuvant systemic therapy (tamoxifen or CMF [cyclophosphamide-methotrexate-5-fluorouracil]) appropriate to the oestrogen-receptor status of the tumour, indicated that this was not so.35 After six years of follow-up, locoregional relapse rates in the non-irradiated group were 24.5%, compared with 5.8% in those irradiated. This does not mean that no patients can safely be treated by local excision alone, but that more precise methods of selection are required before this can be recommended. A number of factors affect relapse rates after local excision and radiotherapy. These include tumour size, the extent of an in-situ component and histological grade. However, the need for complete excision with "clear margins" overrides other considerations, and it is essential that surgeons ensure accurate margin assessment. Biopsy of the excision cavity (cavity shavings) is reported to increase the accuracy of margin assessment.37 The axilla Some surgeons still perform complete dissection of the axilla for all invasive breast cancers; others advise routine radical radiotherapy. Neither approach is logical; an uninvolved axilla needs no treatment. Trials in Edinburgh have shown that sampling fewer axillary nodes (four nodes) provides adequate information on axillary node status, but, as this requires exposure of the axilla under general anaesthesia, it is appropriate only if radiotherapy is the preferred treatment for the involved axilla.38-40For staging the axilla, sentinel node biopsy is under intensive study. The sentinel node or nodes, the first node to which lymph drains from the tumour, can be marked by injecting blue dye or a radioactive marker around the breast tumour.41,42 With the former, visualisation of the axillary contents is necessary, but a radioactive marker allows precise identification of the sentinel node in the operating room with a hand-held gamma probe. The node can be removed with minimal disturbance to other tissues. Some surgeons advocate immediate examination by frozen section, and, if the sentinel node is shown to be involved, a full axillary dissection can proceed. However, frozen section examination is less accurate for node assessment,43 and histopathological examination of the suspected node is preferred practice. If the node can be identified by radionuclear scanning, it can be removed under local anaesthesia before final treatment is planned. Cytokeratin immunostaining improves the accuracy of detection of metastases, but is not appropriate for peroperative assessment. Many surgeons are already practising sentinel node biopsy, but, as recently stressed, the definition of a best method and its evaluation under controlled conditions is required before sentinel node biopsy can be regarded as an acceptable alternative to axillary sampling or clearance.44,45 Systemic therapy Despite evidence that ovarian ablation, tamoxifen and chemotherapy appropriate to the oestrogen-receptor status of the tumour increases this benefit, most surgeons do not advise adjuvant systemic therapy in small node-negative tumours.5-7 Yet, a small proportion of these are still aggressive and cause rapid death. There is a need for tumour markers which can predict likely outcomes for these small tumours; in the meantime, histological grade (as used in the Nottingham Prognostic Index), oestrogen-receptor status and possibly expression of C-erb B2 (HER-2) are the only markers routinely available.46The Nottingham Prognostic Index,47 which combines the size and histological grade of the tumour with the status of the axillary lymph nodes, has been validated in several studies as a reliable prognostic indicator in symptomatic breast cancer.48This Index has also been applied to predict mortality differences in the UK randomised trial of frequency of screening,49 but in a recent study of its application to the Edinburgh randomised trial of screening we have found that the inclusion of more detailed discrimination of size and also of histological type improves prediction in screen-detected cancers (Dr T J Anderson, Pathologist, Department of Pathology, University of Edinburgh, personal communication). Ductal carcinoma in situ (DCIS) Mammographic screening detects an increased number of cases of DCIS,11 but the natural history of the disease is not well understood. In an extensive review of 11 760 excisional breast biopsies performed for accepted benign conditions, 28 DCIS were identified for which a 24-year follow-up was available.50 Invasive breast cancer developed in nine of the 28 patients (32%). However, all were of favourable (non-comedo) type and had been excised, although the completeness of the excision was unknown. These figures may underestimate the true risk in those with more aggressive comedo-type of disease, but it is clear that there is a need for effective treatment. Some surgeons still advocate mastectomy as the only means of guaranteeing cure, but this can no longer be regarded as best practice for other than extensive disease. In Europe, local excision with radical radiotherapy is the preferred option. Features influencing relapse include size, architecture, the presence or absence of necrosis, and cytological nuclear grade.51 However, the factor of overriding importance is the completeness of surgical excision as indicated by free margins.52 Management options have recently been reviewed,53 and three randomised trials are in progress. The results of two trials (NSABP B-17 and B-24, and EORTC 10853) have been reported, the EORTC trial in abstract only.54,55 In B-17 local excision alone (403 patients) and local excision plus radiotherapy (411 patients) are compared. At a median follow-up time of eight years, local relapse was reported in 104 (25.8%) of the non-irradiated group (53 invasive) versus 47 (11.4%) of the irradiated patients (17 invasive). The EORTC trial, which included 1011 patients, had a similar design. At a median follow-up time of 51 months, the cumulative incidence of ipsilateral local recurrence was reduced in the radiotherapy arm (9% v 16%), this including both non-invasive and invasive cancers.56 Only limited information on the completeness of excision is available.57 In the B-24 trial, of 1804 women with DCIS treated by local excision and radiation, half were randomly allocated to receive tamoxifen 20 mg daily for 5 years and half to receive placebo. At a median follow-up of 74 months in women treated by tamoxifen, the cumulative incidence of recurrent breast cancer in either breast was 8.0%, compared with 12.7% in the placebo group; 3.9% and 6.5%, respectively, were invasive.55 It is essential that, as with small invasive tumours, eligible patients with DCIS are entered into randomised trials so that best management can be determined on scientific grounds. A recent survey of practice by 110 surgeons in the south of England showed that, although all four options of local excision, radiotherapy and tamoxifen were being used electively, only 27% of patients were included in the UK trial which compares them, a lamentable disregard of the need for evidence-based practice.58 The future -- specialised, multidisciplinary services Mammographic screening has increased the complexity of breast cancer management. Women with breast cancer must be aware of these complexities, understand the reliability of diagnostic methods, the safety of breast conservation, reasons for not advising systemic therapy and policies of after-care and support. Only then can they participate in decision making. Their questions can no longer be answered with authority by an individual surgeon, but require multidisciplinary input by radiologists, clinical and medical oncologists and pathologists supported by a breast-care nurse or counsellor. The experience of multidisciplinary assessment within the screening service led to the development of a specialised service in Edinburgh for women with symptomatic breast disease. Initially sited in a small hospital equipped with mammographic and operative facilities, this unit has now been transferred to the large Regional Cancer Centre as the Edinburgh Breast Unit, which, although still having independent diagnostic and inpatient facilities, has ready access to sophisticated diagnostic and treatment methods, including computed tomography and magetic resonance imaging, radiotherapy, chemotherapy and all aspects of supportive care. In the UK, women are coming to expect comprehensive care by breast specialists. In Australia, with its emphasis on provision of healthcare by individual practitioners, as well as problems of distance between the major population centres, such a similar pattern may be more difficult to achieve but is likely to be demanded. Acknowledgements We are grateful to Ms Gil Morton for providing facilities in Melbourne for the initial preparation of this paper; to Mrs Ruby Wood for assistance, and to Professor James Garden and the Hunter Research Fund for support. References Breast cancer screening. Report to Health Ministers of England, Wales, Scotland and Northern Ireland by Working Group chaired by Sir Patrick Forrest, 1987. London: HMSO, 1987. Australian Institute of Health and Welfare. Breast and cervical cancer screening. Canberra: AIHW, 3-27. Brinkley B, Haybittle JL. The curability of cancer. Lancet 1975; 2: 951. Kerr GR, Kunkler IH, Langlands AO, Rodger A. (In)curability of breast cancer: a 30 year report of a series of 3933 cases. Breast 1998; 7: 90-94. Early Breast Cancer Trialists' Collaborative Group. Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet 1996; 348: 1189-1196. Early Breast Cancer Trialists' Collaborative Group. 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Lindor NM, Green MH and the Mayo Familial Cancer Programme. The concise handbook of family history syndromes. J Natl Cancer Inst 1998; 90: 1039-1071. Hanley B. BRCA genes -- bookmaking, fortune telling and medical care [editorial]. N Engl J Med 1997; 336: 1448-1449. Krainer M, Silva-Arrieta S, Fitzgerald MG, et al. Differential contributions of BRCA1 and BRCA2 to early onset breast cancer. N Engl J Med 1997; 336: 1416-1421. Cancer Research Campaign Report. A way of diagnosing some cancers early and trying to prevent them. London: CRC, 1997. Kirk J, Tucker K. National Best Practice Guidelines for Familial Cancer Clinics. Sydney: NHMRC National Breast Cancer Centre, 1997. Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340: 77-84. Schrag D, Kuntz KM, Garber JE, Weeks JC. Decision analysis -- effects of prophylactic mastectomy and oophorectomy in life expectancy among women with BRCA1 or BRCA2 mutations. N Engl J Med 1997; 336: 1465-1471. Fisher B, Constantino JP, Wickerman DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998; 90: 1371-1388. Veronesi U, Maisonneuve P, Costa A, et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Lancet 1998; 352: 93-97. Powles T, Eeles R, Ashley S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998; 352: 98-101. Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomised trial. JAMA 1999; 281: 2189-2198. Scottish Breast Cancer Audit 1987 and 1993. Report to Chief Scientist and CRAG by Scottish Cancer Focus Group and Scottish Cancer Trials Breast Group. Edinburgh: Scottish Cancer Therapy Network,1996. Fisher B, Bauer M, Margolese R, et al. Five year results on a randomised trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985; 312: 665-673. Clark RM, Whelan T, Levine M, et al. Randomised clinical trial of breast irradiation following lumpectomy and axillary dissection for node negative breast cancer: an update. J Natl Cancer Inst 1996; 88: 1659-1664. Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast preserving surgery in women with localised cancer of the breast. N Engl J Med 1993; 328: 1587-1591. Liljegren G, Holmberg L, Adami H-O, et al. Sector resection with or without postoperative radiotherapy for stage 1 breast cancer: five year results of a randomised trial. J Natl Cancer Inst 1994; 86: 717-722. Forrest AP, Stewart HJ, Everington D, et al, on behalf of Scottish Cancer Trials Breast Group. Randomised controlled trial of conservation therapy for breast cancer 6 year analysis of the Scottish Trial. Lancet 1996; 348: 708-713. Fisher B, Anderson S, Fisher ER, et al. Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet 1991; 338: 327-331. Macmillan RD, Purushotham AD, Mallon E, et al. Breast conserving surgery and tumour bed positivity in patients with breast cancer. Br J Surg 1994; 81: 56-58. Steele RJC, Forrest APM, Gibson T, et al. The efficacy of lower axillary sampling in obtaining lymph node status in breast cancer: a controlled randomised trial. Br J Surg 1985; 72: 368-369. Forrest AP, Everington D, McDonald CC, et al. The Edinburgh randomised trial of axillary sampling or clearance after mastectomy. Br J Surg 1995; 82: 1504-1508. Chetty U, Jack W, Dillon P, Prescott R. Axillary surgery in patients with breast cancer being treated by breast conservation: a randomised trial of node sampling and axillary clearance. Breast 1997; 6: 226. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994; 220: 391-401. Veronesi U, Paganelli G, Galimberti V, et al. Sentinel node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet 1997; 349: 1864-1867. Dixon JM, Mamman U, Thomas J. Accuracy of intraoperative frozen-section analysis of axillary nodes. Br J Surg 1999; 86: 392-395. Dixon M. Sentinel node biopsy in breast cancer. BMJ 1998; 318: 295-296. Anderson JJ. The challenge of sentinel lymph node biopsy. Histopathology 1999; 35: 82-84. McGuire WL, Tandon AK, Allred DS, et al. How to use prognostic factors in axillary node-negative patients. J Natl Cancer Inst 1990; 82: 1006-1015. Haybittle JL, Blamey RW, Elston CW, et al. A prognostic index in primary breast cancer. Br J Cancer 1982; 45: 361-366. Balslev I, Axelsson CK, Zedeler K, et al. The Nottingham Prognostic Index applied to 9149 patients from the studies of the Danish Breast Cancer Cooperative Group. Breast Cancer Res Treat 1994; 32: 281-290. Blamey RW, Day N, Young R, et al. The UKCCCR trial of frequency of breast screening. Breast 1999; 8: 215. Page DL, Dupont WD, Rogers LW, et al. Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade carcinoma in situ treated by biopsy only. Cancer 1995; 76: 1197-1200. Delaney G, Ung O, Bilous M, et al. Ductal carcinoma in situ. Part I: Definition and diagnosis. Aust N Z J Surg 1997; 67: 81-93. Silverstein MJ, Poller DN, Waisman JR, et al. Prognostic classification of breast ductal carcinoma in situ. Lancet 1995; 345: 1154-1157. Delaney G, Ung O, Cahill S, et al. Ductal carcinoma in situ. Part II: Treatment. Aust N Z J Surg 1997; 67: 157-165. Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 1998; 16: 441-452. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of intraductal breast cancer: National surgical adjuvant breast and bowel project B-24 randomised controlled trial. Lancet 1999; 353: 1193. Julien JP, Fentiman I, Bijker N. Ductal carcinoma in situ of the breast (DCIS) EORTC 10853. Breast 1999; 8: 242. Fisher ER, Constantino J, Fisher B, et al. Pathological findings from the national surgical adjuvant breast protocol B-17 intraductal carcinoma (duct carcinoma-in-site). Cancer 1995; 75: 1310-1319. Baker CB, Daltry IR, Kissin MW, on behalf of South Thames-West Breast Screening Programme. Screen detected DCIS: surgeons think they know best. Breast 1997; 6: 229. Authors' details Department of Clinical and Surgical Sciences, University of Edinburgh, and Edinburgh Breast Unit, Western General Hospital, University of Edinburgh, Edinburgh, Scotland. A Patrick M Forrest, Kt, MD, FRCS, FRACS(Hon), Professor Emeritus. Elaine D C Anderson, MD, FRSCEd, Consultant Surgeon and Honorary Senior Lecturer. Reprints will not be available from the authors. Correspondence: Sir Patrick Forrest, 19 St Thomas Road, Edinburgh, EH9 2LR, Scotland, UK. patrick.forrestATed.ac.uk Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> We appreciate your comments. 1: NHS Breast Screening Programme11Program instituted1987Age of women screened50-64 years (younger age under trial) Method of invitationBy personal letterCompliance ratesStrictly monitored (1995-96, 75.8%)Frequency of scanningEvery three years (optimum frequency under trial)Reading of mammogramsBy experienced radiologists only (read minimum of 5000 mammograms per year). Double reading variableQuality assurance/evaluationFor each specialty, regional and national quality assurance groups (including one for monitoring and evaluation) were set up. National coordinators and advisory committees publish annual reports. Strict auditing of clinical and pathological characteristics (size, node status, grade) of screen-detected cancers (Box 2)Data collectionNational Screening Evaluation Unit maintains a database for the whole UK programResearch organisationNational Breast Screening Reseach Committee of the UK Committee for Co-ordination of Cancer Research Back to text 2: Consistency of screening activity in women over 50 years in the UK NHS Screening ProgrammeVariable1995-961994-95Women invited1 517 0331 507 605Acceptance rate75.876.7Total screened1 222 3891 207 316Recalled for assessment62 682 (5.1%)63 925 (5.3%)Breast biopsy6496 (5.3/1000)6334 (5.2/1000)Benign biopsy2472 (2.0/1000)2000 (1.6/1000)Cancers detected6664 (5.4/1000) 6500 (5.4/1000)In situ (% of cancers)19.9%20.0%Invasive < 15 mm (% of cancers)42.1% 40.9% Back to text 3: Woman with a family history of breast cancer16-20 Genetic mutations: True familial breast cancer may be associated with mutations of BRCA1, causing breast and ovarian cancers and (in men) an increased incidence of cancer of the prostate; BRCA2, predominantly associated with cancer of the breast but also with other epithelial tumours; or p53, causing the rare Li-Fraumeni syndrome. Determining risk: Pedigree analysis is the important first step. In women with more than four family members with a dominant history of breast and ovarian cancer, a mutation of BRCA1 is associated with an 87% risk of either disease. In those with fewer affected family members, penetrance of a mutated gene may be lower, and the risk of breast or ovarian cancer is in the region of 20%-30%. Although breast cancer is more likely to be familial in young women, only a minority have mutations of either gene. In a study of 73 women with breast cancer diagnosed before age 32 years, common mutations of BRCA1 and BRCA2 were detected in only 12% and 2%, respectively.21 Genetic clinics: In the United Kingdom, as in Australia, genetic clinics have been established. In the UK, criteria for referral are based on national guidelines.22 Australian guidelines for genetic clinics, published by the National Breast Cancer Centre, are exemplary and should be stringently followed.23 The genetic service of the screening clinic in Edinburgh offers screening to women whose risk is three times that of the age-specific population risk (a lifetime risk greater than 24%). Screening starts at age 35 years or five years younger than the first index case and includes an annual physical examination and biennial mammographic examination to the age of 40 years; then annual mammography to the age of 50. In families at very high risk, the screening interval is reduced to 18 months in women over 50 years. Genetic testing of blood is currently used only for research. In those with a dominant family history, germline mutations of BRCA1 and BRCA2 are sought from the index case. Prophylactic mastectomy: In a large Mayo Clinic series of 639 women with a family history of breast cancer (214 high risk and 425 moderate risk), prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90%.24 Modelling of life-years gained suggests that benefit from prophylactic mastectomy depends on age and penetrance of the gene, and women must be made aware of the likely benefits, risks and costs, while recognising that regular mammographic screening is a viable alternative to mastectomy.25 The uncritical use of genetic testing has inherent hazards, such as loss of insurance or employment, psychological distress, risk of prophylactic surgery and disruption of family relationships. Chemoprevention: In the National Surgical Adjuvant Breast and Bowel Project (NSABP) trial, 13 388 women considered to be at increased risk of breast cancer were randomly allocated to receive tamoxifen or placebo. Over a mean follow-up period of four years, 89 women who received tamoxifen developed invasive cancer compared with 175 cases in the placebo group, a reduction of 49%.26 Tamoxifen increased the risk of endometrial cancer, pulmonary embolism and deep vein thrombosis. Unfortunately, the NSABP trial was stopped and women in the control group were given tamoxifen before mortality data were available, but two other trials in Milan and London (which to date have shown no reduction in risk) will provide this.27,28 A large international trial (IBIS) is under way. Raloxifene (a selective oestrogen-receptor modulator), recently reported to decrease the risk of newly diagnosed breast cancer in postmenopausal women with no prior history of breast cancer,29 may also be suitable for chemoprevention in patients at high risk of breast cancer. Back to text 4: Trials of conservative therapy for early breast cancerTrialNumber of patientsFollow-up (years)Tumour size (cm)MarginsNSABP B-06*3118435≤ 4.0ClearToronto328377.6< 4.0ClearMilan335673.25< 2.5WideOrebro Uppsala343815≤ 2.0ClearScottish355856≤ 4.01 cmRelapse in ipsilateral breastTrialNode positiveSystemic therapyRadiotherapyNo radiotherapyNSABP B-06*3135.4%Node positive7.7%27.9%Toronto32NoneNone11.3% 35.2%Milan3330.5%Node positive0.3%10.2%Orebro-Uppsala34NoneNone2.3%18.4%Scottish3522.9%All5.8%24.5% *National Surgical Adjuvant Breast Project (B-06). Back to text

Editorial Screening, case finding and evidence-based guidelines There are functional questions about the nature of screening and the exact clinical scenarios to which screening guidelines apply MJA 1999; 171: 344-345 Screening has been defined as "the examination of asymptomatic people in order to classify them as likely or unlikely to have a disease".1 When public health authorities recommend screening for otherwise healthy people they assume a substantial degree of responsibility. Clear evidence should exist that the disease in question can be identified at an earlier and more treatable stage in its natural history. Moreover, the resulting fall in morbidity or mortality should be achieved without too great a burden of adverse effects. In particular, the side effects of the procedures necessary to establish a diagnosis and those associated with the treatments employed should not be excessive. Screening for prostate cancer has spurred considerable controversy, particularly since the introduction of prostate-specific antigen (PSA) testing.2,3 Most authorities within Australia and other countries recommend against such testing.4 The reasons include a lack of confidence that present interventions improve the prognosis of lesions discovered at screening. Furthermore, the interventions available (surgery and radiotherapy) are associated with a fairly high frequency of impotence and incontinence.5 These may be a high price to pay in the absence of proven benefit. Negative sentiments about routine prostate cancer screening have been incorporated into guidelines by four Australian bodies.6-9 In this issue of the Journal, Girgis et al examine the impact of such guidelines on the behaviour of general practitioners faced with a 58-year-old man requesting screening at the behest of his wife.10 They found that 90% of respondents would accede to the patient's request. After being acquainted with the Australian guidelines, three-quarters of the respondents would still choose to test the patient. Only 15% of respondents were confident that the guidelines would assist their case if a patient whom they had refused to test subsequently developed prostate cancer and sued. Few believed that they were at risk of being sued if patients suffered complications of investigation or treatment of which they had not been warned before screening. The authors conclude that evidence-based guidelines have little influence on GPs' approach to prostate cancer screening and raise the issue of "more deliberate implementation". They also regard the lack of confidence in a legal defence derived from national evidence-based guidelines as troubling and recommend that steps be taken to clarify their legal standing. As readers of the discussion in the Journal's Internet peer review trial would be aware,11 these conclusions have been challenged and have raised fundamental questions about the nature of screening and the exact clinical scenarios to which screening guidelines apply. In practice, screening can be carried out in a variety of settings. These range from organised mass population screening to advice provided to a single patient presenting to a doctor on account of some other problems (the latter is referred to as case finding). The common feature is that the medical profession has taken the initiative to promote the testing, and most screening guidelines have been developed with this implicit assumption. If this view is accepted, then a request by a patient to have a PSA test would not qualify as screening. When the request has been made by an asymptomatic patient without any particular concerns, the risk-benefit ratio is likely to be similar to that of a typical screening scenario, and it would be appropriate to be guided by the same advice. In other words, in a setting strictly as described by Girgis et al, where the patient requested testing at the suggestion of his wife, it might well be appropriate to be guided by the same published guidelines for prostate cancer screening. If special concerns about the presence of prostate cancer have led to the request, a GP might reasonably conclude that the extra component of reassurance is sufficient to justify the test. However, men with uncomplicated lower urinary tract symptoms should be advised that there are no data to suggest that they are at increased risk of prostate cancer.9 In real life clinical practice other complexities may also arise and must be taken into account. When patients seek PSA testing, simple refusal is rarely an option for GPs wishing to successfully balance their varied roles of therapist, educator, friend, small businessman and guardian of the public purse. Most GPs would agree that their principal task is to provide a balanced account of the pros and cons of testing. This would include the fact that a positive test could initiate a potentially costly chain of events that might leave the person incontinent and/or impotent without improving his life expectancy. If these facts have been conveyed accurately and the patient still requests testing then continued refusal may be seen as unreasonable and paternalistic. For a simple screening investigation such as PSA, where controversy is known to exist, it is difficult to be critical of practitioners who would provide testing. The other key issue raised by Girgis et al is the extent to which defensive medicine influences the use of clinical investigations in Australia. The fact that 46% of GPs perceived a medicolegal risk if they failed to accede to the patient's request, despite being presented with evidence that the testing was inappropriate, illustrates the extent of this problem. It has been anticipated that the provision of clinical practice guidelines might assist practitioners dealing with controversial clinical problems by providing a legally defensible approach with which to manage patients. However, this study suggests that, at least in the case of prostate cancer screening, guidelines do not provide this reassurance. The authors point out that, unless the legal standing of guidelines can be clarified, they are unlikely to provide a useful response to the problem of defensive medicine. Like many vigorous controversies, the arguments about prostate cancer screening result from a lack of evidence of value rather than evidence of no value. The definitive information to guide practitioners will be derived from clinical trials large enough to establish the balance of benefits and costs in a population. Trials of this type are presently under way in both the United States and Europe.12,13 Findings are expected in 2002 or sometime thereafter. If these provide an unequivocal result, then the response of practitioners to various testing scenarios will be guided by much firmer evidence. John J McNeil Professor, and Head, Department of Epidemiology and Preventive Medicine Monash University, Melbourne,VIC Paul E O'Brien Professor, Department of Surgery Monash University, Melbourne, VIC Mornson AS. Screening. In: Rothman KJ, Greenland S, editors. Modern epidemiology. Philadelphia: Lippincott-Raven, 1998; 499. Mulley AG, Barry MJ. Controversy in managing patients with prostate cancer. Banish dogma, get more data [editorial]. BMJ 1998; 316: 1919-1920. Woolf SH. Screening for prostate cancer with prostate-specific antigen -- an examination of the evidence. N Engl J Med 1995; 333: 1401-1405. Feeney T. To screen or not to screen. In: Fundamentals of prostate cancer detection and treatment [web site]. <http://rattler.cameron.edu/ww/index.html>. Revised 27 January 1999. Accessed 1 September 1999. Coley CM, Barry MJ, Fleming C, et al. Early detection of prostate cancer. Part II: Estimating the risks, benefits, and costs. Ann Intern Med 1997; 126: 468-479. Australian Cancer Society. Prostate cancer screening: guidelines for health professionals. Cancer Forum 1995; 19: 47-50. Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 4th ed. Sydney: RACGP, 1996; 26. National Health and Medical Research Council. Clinical practice guidelines. The management of uncomplicated lower urinary tract symptoms in men. Canberra: Commonwealth of Australia, 1997. Girgis S, Ward JE, Thomson CJH. General practitioners' perceptions of medicolegal risk. Using case scenarios to assess the potential impact of prostate cancer screening guidelines. Med J Aust 1999; 171: 362-366. Girgis S, Ward JE, Thomson CJH. Potential impact using case scenarios of guidelines discouraging prostate cancer screening on general practitioners' perceptions of medicolegal risk [second revised version with peer review discussion]. <http://www.mja.com.au/public/issues/iprs2/girgis/girgisframe.html>. Accessed 1 September 1999. Kramer BS, Brown ML, Prorok PC, et al. Prostate cancer screening: what we know and what we need to know. Ann Intern Med 1993; 119: 914-923. Auvinen A, Tammela T, Stenman U-H, et al. Screening for prostate cancer using serum prostate-specific antigen: a randomised population-based pilot study in Finland. Br J Cancer 1996; 74: 568-572. &copy1; 1999 Medical Journal of Australia.

Abstract Objective: To ascertain general practitioners' perceptions of medicolegal risk when screening for prostate cancer, and explore the potential impact of three national guidelines on perceptions and clinical practice. Design: Postal survey in August 1997. Participants: 219 randomly selected GPs in New South Wales (65% response rate). Main outcome measures: Response to case scenarios; perceptions of medicolegal risk and protection afforded by national guidelines before and after reading extracts of three national guidelines; ratings of current and potential strategies to increase GPs' sense of medicolegal protection. Results: 90% (95% CI, 86.5%-94.3%) would screen an asymptomatic male patient and 61% (95% CI, 54.2%-67.2%) indicated GPs would be at risk if they did not screen. Although significant changes in responses were found after respondents had read guideline extracts, 46% (95% CI, 39.5%-52.7%) continued to perceive medicolegal risk if screening was not performed. About two-thirds (65%; 95% CI, 59.9%-72.5%) supported a clear statement about the legal status of guidelines in a court of law to increase their sense of medicolegal protection. Conclusions: Even when made aware of national evidence-based guidelines against prostate cancer screening, GPs in our survey perceived limited hypothetical medicolegal protection. Introduction In Australia, the risk of medical litigation has increased. For general practitioners, the risk of being sued doubled from 1:160 in 1990 to 1:84 in 1994.1 If doctors believe these risks are substantial, this belief alone may influence their clinical behaviour.2-5Medicolegal risk may be reduced if practice is within existing clinical practice guidelines.6 Prostate cancer screening represents a "test-case" for such guidelines.7 Although there is no evidence that premature mortality from prostate cancer will be reduced by screening (see Box 1), Australian men report high rates of testing.12,13 GPs use prostate-specific antigen (PSA) assays for screening, either alone or combined with digital rectal examination (DRE).11,14,15 Current tests cannot distinguish innocuous from aggressive malignancy.16 Treatment options for men with localised prostate cancer currently available are "unnecessary for some and insufficient for others".17 On current evidence, men's quality of life may be diminished by anxiety, unnecessary treatment and adverse complications if screening is recommended.16 Unsurprisingly, 39% of GPs surveyed in 1995 indicated that prostate cancer screening guidelines would be "extremely" or "very" useful.18 Three sets of guidelines ensued, each recommending against screening.9,19,20 Yet, Pinnock et al recently reported that there is "anecdotal evidence that general practitioners are concerned that if a PSA test is not offered, and prostate cancer is later diagnosed, they may be seen as negligent".13 In a US survey, physicians who perceived that a patient who develops prostate cancer would be successful in suing his physician if he had not been previously screened were more likely to report using PSA tests to screen than those who perceived that such litigation would be unsuccessful.21 No published Australian research has quantified the influence of medicolegal concerns on prostate cancer screening. We designed this study to ascertain GPs' perceptions of medicolegal risk when asked to screen for prostate cancer, and, by using case scenarios, to assess the potential impact of national guidelines on their views. Methods Questionnaire The first section of our self-administered questionnaire commenced with this case scenario: Mr Smith, a 58-year-old employed repairman, presents to his regular GP after prompting by his wife to have a test for prostate cancer. He has no urinary symptoms, no family history of prostate cancer and has not had a vasectomy. GPs were asked: when they had last had a similar request; what should be done; whether the GP would be at risk medicolegally if she or he either did or did not perform either or both tests for screening purposes; what they would do if they were the GP and which test(s) they would advise as being the best available. We also randomised respondents to receive one of two versions of the case scenario which were identical, except that in one the patient was an architect, and in the other he was a repairman. We next provided verbatim the policies of the Australian Cancer Society,9 the National Health and Medical Research Council (NHMRC)19 and the Royal Australian College of General Practitioners (RACGP)20 about screening for prostate cancer, and asked if the respondents were aware of each guideline and whether, having read excerpts from all three, they would change their answers to the initial scenario. We then repeated the first scenario and questions. Our second case scenario read as follows: Imagine the following scenario with the earlier patient, Mr Smith. Having presented for a PSA test, you discouraged him from having it. Imagine that six months later, he is diagnosed with prostate cancer after a blood test organised by a locum. He then proceeds with a formal complaint against you because you did not do the test when he first requested it. We asked respondents to indicate if the three guidelines would protect them in the event of such a complaint, the extent to which such a possibility influenced their practice, and their perceptions of the likelihood of such a scenario. We next asked respondents to indicate their opinion of each of seven statements about prostate cancer screening, using a five-point Likert scale. Respondents then ranked five current and 14 potential strategies to increase GPs' sense of medicolegal protection in this aspect of clinical practice. The questionnaire concluded with six sociodemographic questions. Survey administration and analysis We purchased a list of all NSW GPs from a commercial company and randomly selected 400 names. Questionnaires and reply-paid envelopes were mailed in mid-1997, after an advance telephone prompt. At Day 16, non-responders received a reminder letter. At Day 35, a second questionnaire was posted to remaining non-responders. Two weeks after the second mail-out, a research assistant telephoned any remaining non-responders. The initial sample size was calculated to yield at least 200 questionnaires for analysis, thereby permitting independent and paired univariate analyses. Descriptive statistics were calculated, using SPSS version 6.0.22 We used univariate analysis to examine differences in GPs' responses to either repairman or architect scenarios. Univariate analysis was also performed to determine significant associations between respondents' beliefs and five nominated outcome variables. For these analyses, categories were collapsed into dichotomous variables. McNemar's χ2 was used to determine differences in GPs' responses to the scenarios before and after reading the three guidelines. The Royal Prince Alfred Hospital Ethics Committee approved the study. Results Of the 400 randomly selected GPs, 64 were ineligible (2 dead, 9 retired, 25 not in general practice, 5 on extended leave, 8 outside Australia, 15 uncontactable). From the 336 eligible GPs, 219 (65%) usable questionnaires were received. Our sample comprised 161 male respondents (74%) and 55 female respondents (26%), compared with 68% and 32%, respectively, for the NSW reference sample.23 Median age of our respondents was 47 years (range, 28-70 years); half had been in general practice for more than 17 years (range, 1-47 years) and 127 (58%) worked in the Sydney metropolitan area, somewhat comparable with the NSW reference sample (51% aged 45 years or over and 70% practising in Sydney).23 As only proportions (not actual numbers) for the NSW sample have been published,23 statistical testing of response bias was precluded. Responses to Scenario 1 Of the 219 GPs, 116 (53%) had received the repairman version of the case scenario and 103 (47%), the architect. There was no significant difference in GPs' answers to management of a patient's request for screening before (odds ratio [OR], 0.6; 95% CI, 0.19-1.85; P = 0.4) or after (OR, 0.79; 95% CI, 0.38-1.63; P = 0.5) reading the guidelines. Responses to all scenarios were therefore combined irrespective of patient occupation. More than two-thirds (95% CI, 62.8%-75.0%) of the participating GPs had had a request for prostate cancer screening from an asymptomatic man within the previous week (21.9%; 95% CI, 16.4%-27.4%) or the previous month (47.0%; 95% CI, 39.9%-53.2%). Of the total sample, 52.5% (95% CI, 45.9%-59.1%) indicated that PSA and DRE in combination should be done if a man requested a screening test and 55.3% (95% CI, 48.7%-61.9%) would perform the two tests (Box 2). The proportion of GPs perceiving that the GP would be at medicolegal risk if she or he did not screen for prostate cancer (61.2%) was significantly higher than that perceiving a risk if she or he did screen (15.1%; OR, 0.13; 95% CI, 0.03-0.44; P < 0.001) (Box 3). Only a quarter of the sample was aware of all three guidelines used in our survey (24.2%; 95% CI, 18.5%-29.9%). After reading the guidelines, significantly more respondents perceived less medicolegal risk if not proceeding to screening (Box 3). In addition, more respondents perceived risk if proceeding to screening (Box 3). Twenty-eight per cent (95% CI, 21.96%-33.8%) indicated that, given the three sets of guidelines, the GP would be protected medicolegally if screening tests were not performed (Box 3). Responses to Scenario 2 In the second case scenario, 14.6% (95% CI, 9.92%-19.3%) of respondents thought that the three guidelines would "most likely" protect them in the event of such a complaint. Respondents who thought such a scenario would "most likely" or "likely" influence their practice (68.9%; 95% CI, 62.8%-75.0%) were significantly more likely than those indicating it "unlikely" (23.7%; 95% CI, 18.1%-29.3%) to consider such a scenario could happen (OR, 2.72; 95% CI, 1.48-5.0; P = 0.0001). Compared with respondents who had stated, after reading the three Australian guidelines, that they would not screen an asymptomatic man, those who had stated they would screen were significantly less likely to indicate that guidelines would protect them medicolegally (OR, 0.08; 95% CI, 0.03-0.19; P < 0.001). Respondents who did not indicate that the GP would be at risk medicolegally if she or he did not perform any screening test were significantly more likely to consider that the guidelines would protect them than those who did (OR, 8.76; 95% CI, 4.45-17.23; P < 0.001). GPs who had reported that they would change their response to the case scenario after reading the guidelines presented in the survey were significantly more likely to think that the guidelines would protect them compared with those who had reported that they would not (OR, 2.55; 95% CI, 1.34-4.88; P = 0.004). GPs' views about influences on prostate cancer screening Box 4 summarises responses to seven statements about prostate cancer screening in general practice. Of the sample, 87.2% (95% CI, 82.8%-91.6%) "strongly agreed" or "agreed" that patients' decisions to be screened should be based on full disclosure of what is known about diagnosis and treatment of early prostate cancer. Respondents were significantly more likely to agree that a GP could be sued by a patient who subsequently developed prostate cancer for not performing a PSA test than by a patient who subsequently experienced adverse consequences of treatment resulting from a PSA test which had been performed (OR, 2.98; 95% CI, 1.22-8.34; P = 0.01). GPs' views of strategies to increase their sense of medicolegal protection In rating five current strategies to increase their sense of medicolegal protection, 50% (95% CI, 43.6%-56.8%) of respondents considered guidelines based on systematic reviews of the evidence as "very important", followed by NHMRC endorsement (44%; 95% CI, 37.2%-50.3%), quality of patient information (44%; 95% CI, 37.2%-50.3%) and availability of patient information about prostate cancer screening (38%; 95% CI, 31.96%-44.8%). A minority (11%; 95% CI, 6.9%-15.1%) were unsure of the impact of the current adversarial court system, which is seen as adversarial rather than conciliatory. With regard to potential strategies, there was strong support for written advice about the legal status of guidelines and inviting GP peers as well as specialists as expert witnesses in court (Box 5). Discussion Evidence-based guidelines appear to have little influence on GPs confronted by an asymptomatic man requesting prostate cancer screening. At least 90% of respondents in our study would proceed with at least one screening test (DRE, PSA, or both in combination). Furthermore, a significant majority of respondents considered the GP in the first scenario would be "at risk" medicolegally if she or he did not screen, and more so than if she or he did screen. Awareness of national guidelines was low. Surveys repeatedly demonstrate poor penetration of guidelines into general practice,24 generating interest in more deliberate implementation.7,25,26Our proxy for assessing the impact of guidelines on clinical practice augurs poorly for their influence in reducing perceptions of risk of being sued. Although, after reading the guidelines, significantly fewer considered the GP was at risk if she or he did not screen, only 28% indicated the GP was protected medicolegally by three sets of evidence-based guidelines when complying with their recommendations against screening. Even fewer (15%) considered protection would be afforded them if a man, having been diagnosed elsewhere with prostate cancer, then proceeded to initiate legal action for previous failure to screen. Those who perceived such a situation was likely were also more influenced by it in their practice. In contrast, those who would not screen were more likely to feel protected by guidelines. Most of the respondents supported a clear statement about the legal status of guidelines in a court of law. This is in contrast to the recommendation of a forum held in 1997 to examine legal implications of guidelines.27 Our results also confirm the observation of Pinnock et al that prostate cancer screening can be motivated by medicolegal concerns.13 In the US, physicians' self-reported screening correlates with their views about a medical malpractice vignette.21 Our findings suggest this to be the case also in Australia, prompting us to agree that "if physicians perform PSA tests at least to some extent out of fear of malpractice, then the standard of care may eventually be set by these defensive practices".21 GPs nonetheless support "informed decision-making" by men themselves. Specifically, 88% of the respondents "agreed" or "strongly agreed" that men's decisions to be screened should be based on "full disclosure" of what is known about the diagnosis and treatment of early prostate cancer. Two methodological caveats are recognised. First, the validity of our use of scenarios before and after exposure to guidelines has not been formally tested against actual behaviour. However, we know of no other feasible method to examine perceptions of medicolegal risk on test-ordering. Second, our response rate (65%) was lower than we had hoped, but the professional and demographic characteristics of our sample were comparable with the NSW GP profile. In summary, GPs in our survey perceived limited medicolegal protection from evidence-based guidelines. Their lack of confidence in a legal defence based on national guidelines is troubling. Those strategies suggested by GPs as important in increasing their sense of medicolegal protection could be considered further by health departments, medical defence organisations and clinical colleges. Acknowledgements The study was conducted while S Girgis was completing the NSW Health Department Public Health Officer Training Program. We thank Geoff Hirst for advice; Drs Buhagier, Stan, Gordon, Foran, Reid, Young, McGuigan and Sladden for their comments as GPs on questionnaire drafts; Nancy Harding for research support; Margaret Lesjak for assisting with telephone prompts; and Neil Donnelly for statistical advice. References Keaney MA. Is there a medical litigation crisis? Individual viewpoints on the perceived medical litigation crisis. Is litigation increasing? Med J Aust 1996; 164: 178-179. Weisman C, Morlock L, Teitelbaum M, et al. Practice changes in response to maplractice litigation climate. Results of a Maryland physician survey. Med Care 1989; 27: 16-24. Kessler D, McClellan. Do doctors practice defensive medicine? National Bureau of Economic Research working paper series. Cambridge, 1996. Summerton N. Positive and negative factors in defensive medicine: a questionnaire study of general practitioners. BMJ 1995; 310: 27-29. Hancock L. Defensive medicine and informed consent: a research paper. Review of professional indemnity arrangements for health care professionals. Canberra: AGPS, 1993. Barratt A, Bates P. O tell me the truth about evidence. Aust N Z J Public Health 1997; 21: 441-444. Ward J. Prostate cancer screening: too much, too soon? Cancer Forum 1998; 22: 18-23. Report of the US Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore: Williams & Wilkins, 1996; xlii. Australian Cancer Society. Prostate cancer screening: guidelines for health professionals. Cancer Forum 1995; 19: 47-50. Wald N, Morris J. What is case-finding? J Med Screening 1996; 3: 1. Ward J, Young J, Sladden M. General practitioners' views and use of tests to detect early prostate cancer. Aust N Z J Public Health 1998; 22: 374-380. Ward J, Hughes AM, Hirst G, Winchester L. Men's estimates of prostate cancer risk and self-reported rates of screening. Med J Aust 1997; 167: 250-253. Pinnock C, Weller D, Marshall V. Self-reported prevalence of prostate-specific antigen testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Sladden M, Dickinson J. General practitioners' attitudes to screening for prostate and testicular cancer. Med J Aust 1995; 162: 410-413. Ward J, Gupta L, Taylor N. Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer? Med J Aust 1998; 169: 29-31. Hirst G, Ward J, Del Mar C. Prostate cancer screening: the case against. Med J Aust 1996; 164: 285-287. Whitmore W. Management of clinically localised prostate cancer: an unresolved problem. JAMA 1993; 269: 2676-2677. Gupta L, Ward J, Hayward R. Future directions for clinical practice guidelines: needs, lead agencies and potential dissemination strategies identified by Australian general practitioners. Aust N Z J Public Health 1997; 21: 495-499. Australian Health Technology Advisory Committee. Prostate Cancer Screening. Canberra: AGPS, 1996. Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 4th ed. Sydney: RACGP, 1996; 26. Collins M, Fowler F, Roberts R, et al. Medical malpractice implications of PSA testing for early detection of prostate cancer. J Law Med Ethics 1997; 25: 234-242. SPSS for Windows [computer program]. Version 6.0. Chicago Ill: SPSS Inc, 1992. Commonwealth Department of Health and Family Services. General practice in Australia: supplementary tables 1997. Canberra: GP Branch, 1997; 19. (Publication no. 1838.) Gupta L, Ward J, Hayward R. Clinical practice guidelines in general practice: a national survey of recall, attitudes and impact. Med J Aust 1997; 166: 69-72. Hirst G. Clinical practice guidelines -- to what end? [letter]. Med J Aust 1997; 167: 288. Puech M, Ward J, Hirst G, Hughes AM. Local implementation of national guidelines: what do general practitioners suggest will work? Int J Qual Health Care 1998; 10: 339-343. Pelly JE, Newby L, Tito F, et al. Clinical practice guidelines before the law: sword or shield? Med J Aust 1998; 169: 330-333. (Received 7 Oct 1998, accepted 5 Jul 1999) Authors' details Needs Assessment and Health Outcomes Unit, Sydney, NSW. Seham Girgis, MB ChB, MPH, Public Health Officer; Jeanette E Ward, PhD, FAFPHM, Director, and Clinical Associate Professor, Department of Public Health and Community Medicine, University of Sydney. Australian Institute of Health, Law and Ethics, Sydney, NSW. Colin J H Thomson, BA, LLM, Executive Officer. Reprints: Associate Professor J E Ward, Needs Assessment and Health Outcomes Unit, Central Sydney Area Health Service, Locked Bag 8, Newtown, NSW 2042. jwardATnah.rpa.cs.nsw.gov.au 1: Defining "screening" for prostate cancer "Screening" is defined as the testing of asymptomatic individuals to detect risk factors or preclinical disease which has not manifested itself clinically.8 A screening test must satisfy two major requirements to be considered worthwhile: The test must be able to detect the target condition earlier than without screening and not produce large numbers of false positive and false negative results; Screening for and treating persons with early disease should improve the likelihood of favourable health outcomes compared with treating patients when they present with signs or symptoms of disease.8 Community-based randomised controlled trials are in progress to assess whether prostate cancer screening reduces the risk of premature mortality from prostate cancer among men offered it.9 When the results of these trials are published in the peer-reviewed scientific literature, data with which to calculate men's mortality risk in the absence of screening and risk reduction in its presence will be publicly available. The absence of evidence of effectiveness of prostate cancer screening to reduce premature mortality explains why four Australian authorities have recommended against it. Until such evidence is available, "case finding" by GPs who order PSA tests and/or perform DREs on asymptomatic men inadvertently implies prostate cancer screening is worthwhile, even though its effectiveness is yet unproven.10 Inadequate efforts to disseminate evidence-based guidelines to Australian GPs compound this misguided clinical practice, now known to be incorporated at disturbingly high rates in preventive health check-ups.11 In the scenario used in our survey, a 58-year-old man presents to his regular GP after prompting by his wife to have a test for prostate cancer. Testing in this context equates with screening, irrespective that the man has requested it himself. Back to text 2: Tests recommended by general practitioners in response to a patient request before and after reading extracts from the national guidelines (n=219)Which test should be done?Which test would you do?BeforeAfterBeforeAfterDRE and PSA53%37%55%43%DRE alone31%19%28%18%PSA alone4%7%7%12%Neither10%32%6%19%†DRE = digital rectal examination. PSA = prostate specific antigen. *McNemar's χ2 = 47.02; P < 0.001. †McNemar's χ2 22.78; 1 df; P < 0.001. Bold indicates a response consistent with the national guidelines. Where columns do not add to 100%. Data are missing. Back to text3: General practitioners' perception of medicolegal risk before and after reading the guidelines (n=219BeforeAfterIs the GP at risk medicolegally if she or he does not perform either or both tests for screening?Yes61%46%No26%42%Unsure13%11%McNemar χ2=20.02; 1 df; P < 0.0001Is the GP at risk medicolegally is she or he does perform either or both tests for screening?Yes15%19%No69%62%Unsure16%18%McNemar χ2=4.05; 1 df; P = 0.041Given the three recommendations, is the GP protected medicolegally if she or he does not perform either or both tests for screening?Yes-28%No-33%Unsure-33%Bold indicates a response consistent with the national guidelines. Where columns do not add to 100%, data are missing. Back to text4: General practitioners' views about seven statements pertinent to prostate cancer screening (n=219)Strongly agreeAgreeUnsureDisagreeStrongly disagreePatients' decisions to be screened should be based on full disclosure of what is known about the diagnosis and treatment of early prostate cancer46%42%5%6%1%A positive PSA test result may cause unnecessary anxiety for the patients25%62%3%9%1%A GP could be sued for not ordering a PSA test for someone who subsequently develops cancer of the prostate.16%43%12%20%7%A positive PSA test result leads to investigations and treatments of unknown effectiveness10%44%14%27%3%A GP could be sued for ordering a PSA test for someone who subsequently experiences adverse consequences from treatment6%18%25%35%16%A positive PSA result will lead to investigations associated with unacceptable morbidity3%20%21%49%6%Patients should sign a 'consent form' explaining benefits and potential complications of PSA testing before the GP orders it7%14% 23%41%14%Where rows do not add to 100%, data are missing. Back to text 5: Percentage of respondents rating as "very important" 14 potential strategies to increase a sense of medicolegal protection (n=219) GuidelinesClear statement about the legal status of the guidelines in a court 65%That guidelines summarise any relevant medicolegal judgments44%Public educationPamphlets for patients about prostate cancer screening tests in languages other than English 49%Mass media campaign targeting men older than 50 years which reassures men that screening is ineffective44%A standard consent form explaining benefits and consequences of prostate-specific antigen screening which would need to be signed by the man before he has the test29%A standard consent form also available in languages other than English27%CourtsRequiring a peer expert GP as well as a specialist as expert witnesses66%Legislation that a false screening report does not of itself establish negligence59%Requiring all expert witnesses refer to evidence-based guidelines in court56%Requiring peer expert GPs instead of expert specialists as expert witnesses53%Expert panels to advise the judge instead of juries49%A system of "No fault compensation"46%Removing cases of malpractice from the adversarial legal system46%Juries to include members with medical backgrounds in medicolegal cases35% Back to text

Seham Girgis · Jeanette E Ward

Editorial Breaking bad news: explaining cancer diagnosis and prognosis Doctors and nurses need training in communicating information about cancer and responding to patients' concerns MJA 1999; 171: 288-289 For related articles see Prince, Lobb et al & Naganathan et al Most patients, if they have cancer, want to be told about it, and they want to know what the likely treatments are, the side effects of treatment and their prognosis.1 A clear understanding of prognosis can be particularly important in conditions such as breast cancer, because patients need prognostic information to make informed decisions about systemic treatment. So, how can this information best be communicated? Based on a literature review and recommendations of a consensus panel of doctors (with input from patients with cancer), Girgis and Sanson-Fisher2 published some useful guidelines on conveying information to patients about serious disease or death. Their guidelines included ensuring privacy and allowing adequate time, assessing patients' understanding, giving information about diagnosis and prognosis simply and honestly, avoiding euphemisms, encouraging patients to express feelings, being empathic, giving a broad but realistic time-frame concerning prognosis, and arranging a review. The crucial question is how well these recommendations are followed in clinical practice, as discussing prognosis should be part of the process of breaking bad news. Audiotape recordings of consultations have shown that doctors break the bad news of a cancer diagnosis to patients in a predictable and routine way regardless of patients' individual information needs.3 Although the doctors gave reassurance that something could be done, few attempted to elicit patients' thoughts and feelings about the symptoms and their cause. They gave the information in a consistent order -- diagnosis, the relevant evidence, the need for further investigations, the treatments being considered and the probable outcome -- with no heed to which issues patients wished to address first. Obvious verbal and non-verbal cues of distress were not acknowledged and patients' immediate concerns were not explored. This consultation structure led patients to believe they were not entitled to talk about their feelings or their major concerns. Consequently, their preoccupation with these feelings and concerns meant that they did not assimilate the information and advice given. On being interviewed at the end of the consultation, patients reported that they were left with important, but undisclosed, concerns and also felt that the information given had been inadequate for their needs. The important article by Lobb and colleagues4 published in this issue of the Journal looks at one aspect of breaking bad news to cancer patients -- explaining prognosis to women with breast cancer. It was clear from the women's answers to a questionnaire and a clinical vignette that many had problems understanding prognostic information in the form it is usually presented. The women also varied considerably in what prognostic information they would like to receive and how they preferred it to be presented. The study's findings showed that not all women will desire or understand standard methods of giving prognostic information. It has been suggested that giving patients the opportunity to talk with nurses after consultations in which they have been told they have cancer, or have been given complex information about cancer prognosis, would result in their disclosing concerns and misunderstandings and these could then be fed back to the treating clinicians.5 However, this solution ignores important evidence that nurses are just as reluctant as doctors to acknowledge patients' distress and elicit their underlying concerns.6 Like doctors, nurses in these situations have been found to adopt behaviours designed to prevent further disclosure.7 These "blocking behaviours" include telling patients that any distress is normal, switching the subject to neutral topics, giving information and advice before patients' concerns have been identified, focusing only on physical aspects of the condition, and using leading, closed and multiple questions.7 Doctors and nurses avoid exploring patients' feelings and concerns because they fear that it will provoke too much emotion, which could be harmful to patients.8 They feel that their training has not equipped them with the necessary skills to explore these issues and respond appropriately.9,10 Feeling that they are not being supported emotionally and practically by colleagues and supervisors has also been linked to a greater use of these "blocking behaviours".6,11 The lack of adequate training of doctors and nurses in communicating information to patients with cancer can have important negative psychological consequences for the patients. The development of clinical anxiety and depression is more likely when patients have unresolved concerns and perceive that they have been given inadequate information.12,13 So, how can these communication deficiencies be remedied? The data collected by Lobb et al4 could be used as a basis for ongoing research to identify how best to structure and describe prognostic information so that concepts such as "median survival" and "relative risk" are made understandable. It would then be possible to develop training programs in communication skills that teach doctors how to elicit patients' preferences for information about prognosis. The use of intradisciplinary10 and multidisciplinary workshops14 has been advocated. While objective evidence of the value of intradisciplinary workshops is awaited, multidisciplinary workshops have proved successful in helping doctors and nurses acquire key communication skills.14 Despite workshops being effective in changing key communication behaviours, it is not certain how much of what is learnt is applied to clinical practice. Two randomised trials are being conducted in the United Kingdom in an effort to determine this. The Cancer Research Campaign (CRC) Psychosocial Oncology Group is studying whether training doctors in small groups enables them to be more effective in communicating with patients and better able to cope with breaking bad news and dealing with patient concerns. The CRC Psychological Medicine Group is assessing whether senior doctors benefit from six sessions of individual feedback on their "bad news" consultations and whether this results in better patient recall and less patient distress in future consultations (as measured by a patient interview and the Hospital Anxiety and Depression Scale), as well as a reduction in the level of burnout in the doctors themselves. Without systematic training, the breaking of bad news and discussions of cancer prognosis are likely to fall short of existing guidelines and patients' needs and expectations. Consultations of this type can be difficult and painful. Yet, for too long, we have expected doctors and nurses to undertake these difficult tasks without the necessary training and support. G Peter Maguire Consultant Psychiatrist; and Director Cancer Research Campaign Psychological Medicine Group, Manchester, UK Meredith C, Symonds P, Webster L, et al. Informational needs of cancer patients in West Scotland: cross sectional survey of patients' views. BMJ 1996; 313: 724-726. Girgis A, Sanson-Fisher RW. Breaking bad news: consensus guidelines for medical practitioners. J Clin Oncol 1995; 13: 2449-2456. Maguire P. Breaking bad news. Cambridge: Cambridge Handbook of Psychology, Health and Medicine, 1998: 273-275. Lobb EA, Butow PN, Kenny DT, Tattersall MHN. Communicating prognosis in early breast cancer: do women understand the language used? Med J Aust 1999; 171: 290-294. Watson M, Denton S, Baum M, Greer S. Counselling breast cancer patients: a specialist nurse service. Counselling Psychol Q 1988; 1(i): 23-31. Wilkinson SM. Factors which influence how nurses communicate with cancer patients. J Adv Nurs 1991; 16: 677-688. Maguire P. Barriers to psychological care of the dying. BMJ 1985; 291: 1711-1713. Maguire P, Faulkner A, Booth K, et al. Helping cancer patients disclose their concerns. Eur J Cancer 1996; 32A: 78-81. Maguire P, Faulkner A. How to improve the counselling skills of doctors and nurses in cancer care. BMJ 1988; 297: 847-849. Fallowfield L, Lipkin M, Hall A. Teaching senior oncologists communication skills: Results from phase 1 of a comprehensive longitudinal programme in the United Kingdom. J Clin Oncol 1998; 16: 1961-1968. Booth K, Maguire P, Butterworth T, Hillier VT. Perceived professional support and the use of blocking behaviours by hospice nurses. J Adv Nurs 1996; 24: 622-527. Parle M, Jones B, Maguire P. Maladaptive coping and affective disorders in cancer patients. Psychol Med 1996; 26: 735-744. Fallowfield LJ, Hall A, Maguire GP, Baum M. Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial. BMJ 1990; 301: 575-580. Maguire P, Booth K, Elliott C, Jones B. Helping health professionals involved in cancer care acquire key skills -- the impact of workshops. Eur J Cancer 1996; 32A: 1486-1489.

Research Communicating prognosis in early breast cancer: do women understand the language used? Elizabeth A Lobb, Phyllis N Butow, Dianna T Kenny and Martin H N Tattersall MJA 1999; 171: 290-294 For related articles see Maguire, Prince & Naganathan et al Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Oncology Abstract Objectives: To determine the degree to which women with early breast cancer understand the prognostic information communicated by clinicians after breast cancer diagnosis, and their preferences for how this information is presented. Design: Cross-sectional survey conducted within two months of breast cancer diagnosis, using a self-administered written questionnaire. Participants and setting: One hundred women attending five Sydney teaching hospitals and one country hospital, who were diagnosed with early stage breast cancer between January and December 1997. Results: The 100 respondents represented 70% of the 143 women originally approached to participate. Many respondents did not fully understand the language typically used by surgeons and cancer specialists to describe prognosis: 53% could not calculate risk reduction (with adjuvant therapy) relative to absolute risk; 73% did not understand the term "median" survival; and 33% believed a cancer specialist could predict an individual patient's outcome. Women in professional/ paraprofessional occupations understood more prognostic information than non-professional women. There was no agreement on the descriptive equivalent of a "30%" risk, nor the numerical interpretation of a "good" chance of survival. Forty-three per cent of women preferred positively framed messages (eg, "chance of cure"), and 33% negatively framed messages (eg, "chance of relapse"). The information women most wanted was that relating to probability of cure, staging of their cancer, chances of treatment being successful, and 10-year survival figures with and without adjuvant therapy. Conclusions: Our results suggest that misunderstanding is responsible for women's confusion about breast cancer prognosis. Clinicians should use a variety of techniques to communicate prognosis and risk, and need to verify that the information has been understood. Introduction To make informed decisions women with breast cancer must understand what their prognosis is without systemic treatment, and the likely advantages and disadvantages of treatment. While most Australian doctors now tell cancer patients their diagnosis,1 prognosis is less commonly discussed.2 Reticence to provide prognostic information is often based on concerns that the information will be overwhelming, not understood or will destroy hope.3,4 However, it is not clear whether the information itself, or the language used, is the critical feature. Many patients have a poor understanding of their disease and their prognosis,5,6 or have difficulty recalling the information they have been given about their disease.7,8 Similarly, women at risk of developing breast cancer commonly misreport individual and population risk.9 Denial and minimisation of risk are also common psychological reactions to cancer risk notification after screening procedures.10 If it were possible to determine whether patients cannot understand the terminology or mathematics of risk information, or, rather, prefer not to be told or do not absorb the information, clearer directions for best clinical practice in discussing prognosis could be established. Most previous studies on risk communication in cancer have not dealt specifically with issues pertinent to women with breast cancer. In two studies that did, the women surveyed were well down the treatment path and their experience of learning their prognosis was long past.5,11 To our knowledge, there are no reports of women's understanding of specific prognostic information in early breast cancer. We investigated women's understanding of prognostic information and their preferences for the way the information on the risk of their breast cancer recurring after surgery is presented to them. Methods Survey subjects Women were recruited through their treating physician. To ensure input from a range of women, five urban centres attracting referrals from populations with different socioeconomic profiles (Royal Prince Alfred, Royal North Shore, Prince of Wales, St George, and Westmead hospitals, all in Sydney, New South Wales) and one rural centre (Tamworth Hospital, Tamworth, NSW) were approached to participate in the study. Thirteen breast surgeons and 13 medical oncologists from these centres were invited to participate in the study and all agreed. One hundred and forty-three consecutive women newly diagnosed with stage I or II breast cancer at any of the six treatment centres between January and December 1997 were contacted by letter to request their participation. The women received the letter within 2-4 weeks of making their own decisions about adjuvant treatment and within 2 months of their initial diagnosis. (The timing of questionnaire administration was carefully considered to maximise the saliency of the issues while avoiding distressing women making their own treatment decisions.) The letter was followed up by a phone call from the research coordinator, who obtained verbal consent for participation and then sent out the questionnaire by mail. One centre opted to send women a letter signed by their oncologist inviting them to participate in the study. The survey sample included patients of surgeons and medical oncologists in both private and public practice. Women from a non-English-speaking background with insufficient knowledge of English to complete the questionnaire, and women presenting with a second cancer, were excluded. Questionnaire We gathered the data using a self-administered written 17-item questionnaire, designed on the basis of a review of the literature; an analysis of 20 audiotapes of initial oncology consultations with breast cancer patients (collected from two centres -- Royal Prince Alfred Hospital and Westmead Hospital -- during another study undertaken between 1995 and 199712); and expert consultation (a working party set up by the National Breast Cancer Centre). The 20 audiotapes were transcribed and the contents analysed to identify the range of ways in which prognosis was conveyed to patients (eg, absolute and relative risk, cumulative risk, numerical or non-numerical probability, and individual versus population risk). The questionnaire investigated women's understanding of and preferences for these different formats used by doctors for disclosing prognosis and risk information. In addition, a standard hypothetical scenario of adjuvant therapy in early stage breast cancer was included, and women responded to questions applying to that scenario (Box 1). Six of the questions explored women's understanding of different ways in which the risk of breast cancer recurring after surgery could be presented. Two sample questions are shown in Box 2. A "don't know" option was not offered in the items relating to "understanding" in order to force a choice and allow an analysis of common errors in interpretation. The remaining questions focused on the importance of different prognostic information to women's decision making, and on their preferences for presentation of risk - for example: percentages versus numbers (eg, "70%" v. "7 in 10"); numerical versus verbal descriptions of risk (eg, "30%" v. "small"); and positively framed versus negatively framed statements (eg, "70% chance of remaining free of cancer" v. "30% chance of the cancer coming back"). The questionnaire also elicited the women's demographic data and details of their breast cancer diagnosis and treatment (Box 3). Statistical analysis Appropriate sample sizes were calculated using the SAM sample size software package.13 Sample size calculations were based on effect sizes from related studies in patients' level of recall after a variety of interventions. In an Australian study measuring understanding of information presented in an oncology consultation, a sample size of 47 per group was sufficient to detect statistically significant differences of 7% (P < 0.005) in recall between groups. Thus, in a comparison of two patient subgroups (eg, young v. old), a total sample size of 100 would allow us to detect a similar difference in responses in the two groups. A sample size of 100 would also allow detection of a difference of 30% or more (felt to be clinically significant) between subgroups in the proportion of women preferring one presentation of risk versus another, with a power of 0.8 and a significance level of 0.05. A "total understanding" score was calculated by summing correct responses to the six items assessing "understanding". The summary score was normally distributed (K-S Lilliefors .0514). Descriptive statistics were used to identify the percentage of patients understanding and preferring different risk information. Analysis of variance (ANOVA), Student's t tests and χ2 tests of association were used to examine the relationship between demographic variables and outcomes, as appropriate; two-sided tests were used.15 Ethical approval Approval was granted for this study by the Ethics Committee of the University of Sydney, the Central Sydney Area Health Service, the Southern Sydney Area Health Service, and individual hospital ethics committees at Westmead, Royal North Shore and Tamworth hospitals. Results Of the 118 women who agreed to participate in the survey, 100 returned questionnaires (70% of the original 143 women contacted). Demographic data Demographic characteristics of the participants are presented in Box 3. Their mean age was 56 years and most were city dwellers. Just over half had completed the Higher School Certificate, university or some form of tertiary training. The percentage of women with tertiary qualifications was 42% (compared with 37% in the general Australian population16).. Nearly two-thirds worked (or had worked) in professional or paraprofessional occupations, and 22% were working in occupations related to medicine (eg, doctor, nurse, medical receptionist, technician). Questionnaire responses A summary of the women's responses to the questionnaire is given in Box 4. Discussion We have identified some of the problems women with breast cancer experience when trying to interpret prognostic information presented by their doctors. Our results support the hypothesis that it is misunderstanding, not denial, that causes confusion. A considerable number of women in our study did not clearly understand some of the language used to describe the risk of breast cancer recurrence after surgery or how additional treatment might benefit them. Moreover, the response from this group of relatively highly educated women probably represents a "best case" scenario, and, if anything, one might expect understanding to be poorer in the general population of women with breast cancer. These findings have implications for informed consent. Clinicians need to explain what type of prognostic information can be given, and enquire how much of this information women want to hear. They should check very carefully how women have interpreted the information presented to them, and must not assume that, because a woman has already consulted a number of specialists, her prognosis has been conveyed to her and clearly understood. This applies to all patients with breast cancer, but especially those who work in unskilled occupations. It might be argued that our sample was not truly representative, as (i) the women surveyed, having recently been told their diagnosis, may not have been in the best frame of mind to answer the questionnaire clearly and impartially; and (ii) we did not include a similar group of women who had never had breast cancer. Furthermore, patient responses may have been different had the questions concerned personal experience rather than a hypothetical case scenario.5,9,10,19 However, data from Degner et al20 suggest that views expressed by people diagnosed with cancer differ considerably from those of the well population, which underscores the importance of surveying those who have actually been diagnosed with cancer. In addition, we felt that a typical case vignette was the most appropriate tool to control for the influence of individual disease variables and treatment protocols; to reduce the positive bias associated with evaluating one's own treatment team; and to examine all aspects of risk communication in adjuvant therapy. Creative measures to assist women in understanding risk statistics are needed. Bunker et al have recently proposed that a life table constructed from published statistics on national morbidity and mortality may be used to display the likelihood of developing or dying of a disease at any given moment.21 A similar approach could be used to display the likelihood of disease recurrence and premature death after cancer diagnosis. We believe that these and other information aids may contribute to informed patients' involvement in treatment decisions, and a more realistic understanding of prognosis. Acknowledgements We thank Dr Afaf Girgis, Dr Lyn Mann, Ms Kate White, Ms Joan Wilson and Ms Kim Hobbs for their assistance and advice; also the 26 clinicians who participated in this project, and the women who so willingly filled out the questionnaire. The research was funded by the National Health and Medical Research Council National Breast Cancer Centre of Australia. References Charlton RC. Breaking bad news. Med J Aust 1992; 157: 615-621. Butow PN, Kazemi J, Beeney LJ, et al. When the diagnosis is cancer: patient communication experiences and preferences. Cancer 1996; 77: 2630-2637. Oken D. What to tell cancer patients: a study of medical attitudes. JAMA 1961; 175: 1120-1128. Beisecker AE, Helmig I, Graham D, et al. Attitudes of oncologists, oncology nurses and patients from a women's clinic regarding medical decision making with older and younger breast cancer patients. Gerontologist 1994; 34: 505-512. Siminoff LA, Fetting JH, Abeloff MD. Doctor-patient communication about breast cancer adjuvant therapy. J Clin Oncol 1989; 7: 1192-1200. Sheldon JM, Fetting JH, Siminoff LA. Offering the option of randomized clinical trials to cancer patients who overestimate their prognoses with standard therapies. Cancer Invest 1993, 11: 57-62. Dunn SM, Butow PN, Tattersall MHN, et al. General information tapes inhibit recall of the cancer consultation. J Clin Oncol 1993; 11: 2279-2285. Mackillop WJ, Stewart WE, Ginsburg AD, Stewart SS. Cancer patients' perceptions of their disease and its treatment. Br J Cancer 1988; 58: 355-358. Evans DR, Blair V, Greenhalgh R, et al. The impact of genetic counselling on risk perceptions in women with a family history of breast cancer. Br J Cancer 1994; 70: 934-938. Lerman C, Rimer BK, Engstrom PF. Cancer risk notification: psychosocial and ethical implications. J Clin Oncol 1991; 9: 1275-1282. Hughes KK. Decision making by patients with breast cancer: the role of information in treatment decision selection. Oncol Nurs Forum 1993; 20: 623-628. Brown R, Dunn S, Butow P. Meeting patient expectations in the cancer consultation. Ann Oncol 1997; 8: 877-882. Glasziou P. SAM 2.1: a sample size calculator [computer program]. Sydney: NHMRC Clinical Trials Centre, University of Sydney, 1992. Armitage P, Berry G. Statistical methods in medical research. Oxford: Blackwell Scientific, 1994: 397. SPSS Advanced Statistics, TM6.1. Chicago; SPSS Inc, 1994. Australian women's year book. Canberra: Australian Bureau of Statistics, 1997. Degner LF, Kristjanson LJ, Bowman D, et al. Information needs and decisional preferences in women with breast cancer. JAMA 1997; 277: 1485-1492. Bilodeau BA, Degner LF. Informational needs, sources of information, and decisional roles in women with breast cancer. Oncol Nurs Forum 1996; 23: 691-696. Marteau TM. Framing of information: its influence upon decisions of doctors and patients. Br J Soc Psychol 1989; 28: 89-94. Degner LF, Sloan JA. Decision making during serious illness: what role do patients really want to play? J Clin Epidemiol 1992; 45: 941-950. Bunker JP, Houghton J, Baum M. Putting the risk of breast cancer in perspective. BMJ 1998; 317: 1307-1309. (Received 4 Jan, accepted 11 May, 1999) Authors' details University of Sydney, Sydney, NSW. Elizabeth A Lobb, BAdEd, MAppSci, Associate Lecturer, Medical Psychology Unit. Phyllis N Butow, PhD, MPH, Executive Director, Medical Psychology Unit; and Research Co-ordinator, Department of Psychological Medicine, Royal North Shore Hospital. Dianna T Kenny, PhD, MA, Associate Professor of Psychology, Faculty of Health Sciences. Martin H N Tattersall, MD, FRACP, Professor of Cancer Medicine, Department of Medicine. Reprints: Ms E A Lobb, Associate Lecturer, Medical Psychology Unit, Department of Psychological Medicine, University of Sydney, NSW 2006. Email: lizlobbATblackburn.med.usyd.edu.au 1: Hypothetical breast cancer scenario used in the questionnaire Sheila is a 54-year-old woman with breast cancer. Sheila has gone through the menopause. Sheila chose to have her breast cancer (tumour) removed by a lumpectomy, but she also had some of the lymph glands in her armpit removed. Sheila was advised to have radiotherapy after her lumpectomy. Sheila's breast cancer was small, and the lymph nodes under her arm were not affected with cancer. Her tumour contained receptors to oestrogen, suggesting that it may be sensitive to the effects of hormones. Sheila's doctor uses this information to decide if she would benefit from additional treatment. Sheila understands that any additional treatment other than surgery is called "adjuvant" therapy. Adjuvant therapy means giving treatment now after her surgery to try to prevent the cancer returning in the future. Following her breast cancer surgery, Sheila was told of her risk of having her cancer return (her prognosis) if she has no further treatment. This risk can be expressed in different ways. Back to text 2: Examples of questions to assess women's understanding of relative risk reduction Example A: Sheila's doctor told her that 30% of women with a cancer similar to hers will have their cancer come back within 5 years. If Sheila has additional treatment, the risk of her cancer coming back will be reduced by 30%. Tick one only If Sheila has additional treatment this means the risk of her cancer coming back within 5 years is zero. If Sheila has additional treatment this means the risk of her cancer coming back within 5 years is 21%. If Sheila has additional treatment this means the risk of her cancer coming back within 5 years is 30%. Example B: If Sheila's doctor says the median time for her breast cancer to return without further treatment is about 5 years, he/she means: The average time for Sheila's cancer to return is 5 years That 50% of women with breast cancer like Sheila's will have their cancer return within 5 years That the women whose cancer will come back will have it come back within 5 years I don't understand the word "median" Back to text 3: Demographic characteristics of the respondents (n = 100) to a questionnaire about provision of information on breast cancer prognosis*CategoryNumber of participantsAge (mean, 56 years; range, 35-88 years)Postcode City82 Country18Educational level Non-tertiary58 Tertiary42Occupation Professional/paraprofessional63 Non-professional36Marital status Married58 Other41English as first language84Working in medicine-related occupation22Time since diagnosis 1-2 months71 ≥3 months26Treatment for breast cancer Lumpectomy only14 Mastectomy only17 Lumpectomy + R38 Lumpectomy +R + C15 Mastectomy + C15Family member/friend with breast cancer Yes61 No38* Not all categories sum to 100 because of missing data. R = radiotherapy; C = chemotherapy. Back to text 4: Summary of questionnaire responses Understanding of risk Risk concepts tested Absolute risk of relapse: -- 86% of respondents gave a correct response. 30% relative risk reduction, with therapy, of an absolute risk of 30% (sample question A, Box 2): -- 47% gave a correct response; -- 28% thought additional treatment would reduce the risk of relapse to zero; and -- 25% thought the risk would remain at 30%. Median 5-year survival (sample question B, Box 2): -- 27% answered correctly; -- 43% thought it meant "average" survival; -- 10% thought that half the women not having adjuvant therapy would have their breast cancer return within 5 years; and -- 20% did not understand the term "median". Interpretation of a graphical representation of risk: -- 80% of respondents answered correctly. Distinguishing individual risk from population risk: -- 66% gave correct response. -- The remaining women believed that their cancer specialist knew whether or not they would respond to treatment. Association with demographic variables Mean number of correct responses, 3.4 (95% CI, 3.08-3.6); only one woman answered all six questions correctly. Women in professional employment (mean number of correct responses, 3.6 [95% CI, 3.2-4.0]) or paraprofessional employment (mean number of correct responses, 3.4 [95% CI, 3.0-3.8]) understood more prognostic information than women in non-professional employment (mean number of correct responses, 2.5 [95% CI, 1.7-3.4] [F2,87 = 4.24, P = 0.02]). No other variables were found to be associated with understanding of risk (eg, working in a medically related field; having tertiary qualifications; having had surgery, radiotherapy and/or chemotherapy for breast cancer; or time elapsed since consultation in which prognosis was discussed). Interpretation of words versus statistics There was no consistency in respondents' interpretation of "a good chance of remaining free of cancer" in statistical terms, nor agreement on the non-numerical interpretation of "a 30% risk" (17% thought it was a very high or high risk, 34% that it was a medium risk, and 49% that it was a low risk). Preferences for language 44% of respondents preferred "a 70% chance of cure", 13% preferred "a 7 in 10 chance", and the remainder had no preference. 53% of women preferred "a 30% chance of cancer coming back", 38% preferred "a small chance of cancer coming back", and the remainder had no preference. 49% of non-tertiary-educated women versus 24% of tertiary-educated women preferred the descriptive option (a "small" chance) (χ22 = 8.17, P = 0.02). 43% of women preferred the wording "70% chance of cure", 33% preferred "30% chance of the cancer coming back", and 25% had no preference. Preferences for framing of information Reasons given for choosing positively framed prognostic information: "a more positive/optimistic statement" and "encourages determination to manage treatment positively". Reasons given for choosing negatively framed prognostic information: "it emphasises the importance of additional treatment" and "more specific/precise". Importance attributed to prognostic information (Table) Over 90% of respondents regarded information about their chances of being cured, the staging of their cancer, and the chances that the recommended treatment would work as very important to their decision making. Nearly two-thirds of women regarded the 10-year survival rate with adjuvant therapy as very important information, and 45% wanted to know this rate without adjuvant therapy. These percentages are considerably higher than documented in previous studies.17,18 Women's ratings of the importance of different types of prognostic informationPrognostic informationVery importantSomewhat importantNot importantMy chances of being cured94%2%4%What things about my cancer influence my chances of being cured (eg, size of my cancer, whether lymph nodes are involved, etc)92%6%2%The chances that the recommended treatment will work91%7%2%How many women in my situation choosing to have the recommended treatment would be alive in 10 years60%29%11%Statistics about long term outcome of breast cancer50%32%18%How many women not choosing to have the recommended treatment are alive in 10 years45%35%20%The longest anyone in my situation has lived34%19%47%The shortest anyone in my situation has lived30%14%56%The risk of my cancer shortening my life compared with other life events (eg, heart disease, old age)45%23%32%The average time people in my situation have lived44%28%28%Back to text

Elizabeth A Lobb · Phyllis N Butow · Dianna T Kenny

Editorial Cluster investigations: are they worth it? The odds are against finding a cause, but we must address community concerns MJA 1999; 171: 172 The unexpected clustering of rare and often fatal diseases in specific localities gives cause for concern. When it happens, members of the public often draw it to the attention of their doctors, who in turn pass on the information to local public health units or other authorities. The outcomes of systematic investigation of such disease clusters rarely see the light of day in peer-reviewed journals. In that regard the report in this issue of the Journal by Westley-Wise and her colleagues of an investigation into a cluster of leukaemia cases among residents near a major steelworks is unusual.1 What is not unusual, however, is the report's failure to produce a persuasive explanation for the observed cluster, although it usefully reports some ambient benzene levels (levels that are orders of magnitude lower than those known to produce health effects and similarly lower than levels inhaled in cigarette smoke). Of the many studies investigating close case aggregations of any type, only a few have come up with a credible explanation of why the disease cluster exists or have added to knowledge of the causes of disease. Such exceptions would include, for example, the links found between angiosarcoma of the liver and vinyl chloride monomer exposure,2or mercury poisoning in Minamata, Japan.3 These instances demonstrated strong associations that hardly required the sophisticated statistical tools of modern epidemiology to be identified as "possible" causal links. Sadly, experience tells us that almost all cluster investigations will fail to produce insights into environmental disease interactions, and no amount of time, effort and money will change this. This is for a number of reasons. Clusters are by definition based on tiny case numbers. As such, they may not represent the "typical" disease and are not amenable to epidemiological analyses. Further, most reported clusters tend to be of conditions where little or nothing is known of the common causes. There are often controversial theories relating to the condition (eg, the hypothesis that proximity to powerlines can cause cancer). Finally, the supposed environmental-disease links are often impossible to investigate satisfactorily because of the lapse of time or because it is simply not clear what to investigate. The tenfold excess of childhood cancers in the United Kingdom near the Sellafield reprocessing plant4 has been under investigation for a decade, to no avail. Why then do we continue to spend time investigating these phenomena? Why indeed does every state health department in the USA have its own "cluster investigation protocol"? And why did my colleagues and I produce a similar protocol in the UK in 1997?5 Most public health doctors know that having a disease cluster to investigate is a thankless task. Not to have an investigation at all would be regarded with deep suspicion, while investigations with negative results can lead to accusations of a cover-up. On balance, it is better to hold an investigation than not. So the optimistic epidemiologist, hoping that unexpected insights will drop out of the investigation and reveal a truly causal association, adopts a careful protocol to maximise the chances of success. The pessimist feels that at least a sound methodological approach will guard against the reproaches that may follow a negative finding. All the professionals involved are aware that a bad cluster investigation generates considerable disquiet among the public and tends to give them a bad press. Most therefore take the process to be as important as the outcome -- hence the various guidelines. Guides to cluster investigation tend to have a common theme of transparency of action and a candid approach to the concerned parties. They usually suggest various strategies for investigation, one of which is to take the local concern about the cause of the disease cluster as a hypothesis to test. Indeed, testing this hypothesis is often the best "outcome" of any investigation. Westley-Wise et al tested the hypothesis that the leukaemia cluster was caused by pollution from the neighbouring coke-making facilities.1 Their negative findings, if they succeed in allaying local concerns about this point, will be something of a positive outcome. It has to be said that clusters can and do occur fortuitously. It is possible to calculate how often chance events play a part in clustering. This explanation for a cluster, however, is the one least likely to have credibility with those closely concerned. Perhaps the only sensible way forward is to address the underlying issue that usually starts a cluster investigation -- what are the significant causes of a condition? That is best tackled, not by a cluster investigation, but by the combined efforts of laboratory-based sciences and large epidemiological investigations -- usually cohort or case-control studies. This type of effort has been made (internationally) to elucidate the possible causes of childhood leukaemia (a frequent target of cluster investigation). The next year or so will see the assembly of combined and very large datasets that might tell us why this condition appears to "cluster". Possible small risks (such as powerlines) can be found or discounted, and more plausible, but complex, biological phenomena relating to infection in early life can be properly investigated. The latter will be the focus of much attention. Ray A Cartwright Director, Leukaemia Research Fund Centre for Clinical Epidemiology University of Leeds, UK Westley-Wise VJ, Stewart BW, Kreis I, et al. Investigation of a cluster of leukaemia in the Illawarra region of New South Wales, 1989-1996. Med J Aust 1999; 171: 178-183. Baxter PJ, Anthony PP. Angiosarcoma of the liver in Great Britain, 1963-73. BMJ 1977; 2: 919-921. Tsuchiqa K. The discovery of the causal agent of Minamata disease. Am J Indust Med 1992; 21: 275-280. Draper GJ, Stiller C, Cartwright RA, et al. Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation 1963-1990. BMJ 1993; 306: 89-94. Arrundale J, Bain M, Botting B, et al. Handbook and guide to the investigation of clusters of diseases. London: Leukaemia Research Fund, 1997.

Ray A Cartwright

MJA Practice Essentials Psychosocial support, treatment of metastatic disease and palliative care Michael A Ashby, David W Kissane, Geoffrey F Beadle, Alan Rodger MJA 1996; 164: 43-49 Psychosocial support - Principles of oncological treatment of metastatic breast cancer - Complementary or alternative therapies - Palliative care - Conclusion - Acknowledgement - References - Further reading and reference material - Authors' details - - This article deals with four linked but distinct aspects of care for women with breast cancer, with an emphasis on the pivotal role of the general practitioner: Modern medicine is fast recognising the need for psychosocial support of patients; in fact, for an integrated approach to caring for the whole person at all stages of illness. Oncological treatment of metastatic disease needs to be individualised and based on realistic expectations of outcome balanced against side effects. An open dialogue about the role and appropriateness of so-called "alternative" or "complementary" therapies is needed. Despite significant improvements in palliative care quality and access in Australia in the last decade, many practitioners still require support and advice in this demanding area of care (particularly about difficult symptom control). Psychosocial support Women with breast cancer are likely to experience various psychosocial problems at different stages of their illness (Box 1). The most useful way of differentiating between a normal grief reaction and a classifiable psychiatric disorder is to assess the degree to which the distress is generating undesirable personal, family and social effects and to monitor intensity of symptoms. To assist with the diagnosis of depression in the presence of a medical illness, the Endicott9 criteria (depressed appearance, social withdrawal or decreased talkativeness, brooding, self-pity or pessimism, and a lack of appropriate responsiveness in situations that would normally be pleasurable) can be used in place of somatic symptoms like fatigue, anorexia, weight loss and poor concentration. Psychosocial morbidity can extend throughout the family. It has been shown that for those women who enter palliative care programs, substantial psychological morbidity is identifiable in half the patients, a third of spouses and a quarter of their offspring.10 Family-centred care that recognises family members not only as primary care providers but also as second-order patients is essential.7 There is a clear role for general practitioners in this process, as an integral part of good family medicine practice. The themes which need to be addressed are summarised in Box 2. Therapeutic interventions should be appropriate to the stage of the disease and the woman's personal situation (Box 3). Good clinical care requires that medical, surgical and nursing staff provide opportunities for patients to express their concerns, anxieties and preoccupations throughout routine management. Coping skills and cognitive behaviour therapies11 may be more applicable to early stage disease, while supportive psychotherapies which encourage the sharing of feelings about existential concerns are more suited to patients with metastatic cancer.12 Another approach utilises the central concept of loss. Women with breast cancer grapple with many losses -- their health, breast, sense of femininity, confidence, dreams and belief in the future. A primary goal, therefore, is to facilitate adaptive grieving. So-called grief therapy13 can be pivotal in much cancer counselling, particularly in the light of the pervasive pressure on women "to think positively". It is also important to deal with the possibility of death. Education and clarification of fears can help promote a sense of realism-based mastery. Group therapies are cost-effective, provide a supportive network and are acceptable to about two-thirds of women. Pharmacological treatments complement psychotherapeutic approaches (see Box 4). Major tranquillisers and benzodiazepines can allay anxiety, assist in crises and help to contain distressing features of delirium. Tricyclic antidepressants and selective serotonin reuptake inhibitors help in depressive disorders. They are prescribed for major depression, when sleep disturbance or other depressive symptoms are moderate in degree and when poor coping and chronic grief are persisting. Reduced sex drive2 and reduced frequency of intercourse invariably follow the initial diagnosis. Open communication about intimacy and sexuality is desirable and may need to be initiated by clinicians. The general practitioner should be approachable for first contact on these issues. Clarification of the role of altered body image, grief, depression, the nature of the relationship and adjustment of both partners is necessary before endocrine assessment is considered. Although at present psychological interventions are usually offered only to those who have become symptomatic or are perceived to be particularly at risk, recent studies suggesting an association between psychological wellbeing and survival compel us to consider whether such therapies should be offered routinely.12,14,15 The experience of stressful life-events, loss of hope, helplessness, social isolation and failure to share negative emotions have all been associated with poorer outcome.16 Large multicentre replication studies of group therapy for women with both early stage and metastatic breast cancer are currently proceeding in the United States, Canada and Australia, in the hope of clarifying how critical this role of support and coping is to overall survival. Principles of oncological treatment of metastatic breast cancer Metastatic breast cancer is incurable, but effective palliative treatment is possible for most patients. The five-year survival is about 5%-10%. In view of the variable natural history, treatment plans have to be tailored to the needs of each patient. Surgery, radiotherapy and systemic treatments have important and varying roles during the course of the disease. The relative value of each treatment is influenced by the dominant site(s) and distribution of metastastic spread, the severity of symptoms, the general condition of the patient, rate of progression of the disease and response to previous treatments. It is crucial with all forms of palliative therapy -- local or systemic -- that the benefits in terms of symptom control are weighed against the expected toxicities of treatment. The patient must be involved in these decisions as expectations, tolerances and wishes will vary. Advice and support of general practitioners and palliative care staff may be useful to complement the input of the oncologist. Systemic therapies Approximately 30%-35% of patients with metastatic breast cancer respond to endocrine treatment and 60%-70% to cytotoxic drug treatment. Box 5 summarises the principles of selection of these treatments. The therapeutic effect of endocrine treatment is mediated through the oestrogen and progesterone receptors, and the most important single characteristic predicting response to hormone therapy is the original tumour receptor status (rate of response 50%-60% if receptors are present, 10% if absent). Resistance to initial endocrine treatment is associated with a very small chance of a response to subsequent hormone manipulation, but progression after a good initial response is an indication to continue with second and even third line endocrine therapy until the disease becomes hormone resistant. In practice, patients rarely respond to more than two sequential endocrine treatments. Endocrine therapy: For premenopausal patients ovarian ablation (by oophorectomy or radiation) may be replaced by medical treatment with the luteinising hormone-releasing hormone agonists (e.g., goserelin and leuprorelin acetate). For postmenopausal women the antioestrogen tamoxifen and oral progestogens (medroxyprogesterone acetate and megestrol acetate) are the most commonly prescribed treatments. Aromatase inhibitors (e.g., aminoglutethimide and formestane [4-hydroxy androstenedione]) have replaced adrenalectomy for those postmenopausal patients who have exhibited protracted responses to initial endocrine treatment. Chemotherapy: The initial high response rate of metastatic breast cancer to cytotoxic drugs and the eventual development of resistance raise several important issues in management. Combinations of cytotoxic drugs offer a better chance of response than single agents, but do not yield substantially better survival for most patients. The exception is those patients with life threatening visceral metastases (normally in liver and lung). Regimens including anthracyclines (doxorubicin, epirubicin) are the most effective and are useful for aggressive or life threatening disease. Less aggressive disease may be treated with less toxic regimens, frequently based on mitozantrone, although there are a considerable number of alternative options. Second and even third line regimens are indicated when disease progresses after an initial response, but response rate and duration are usually less with each subsequent regimen. All treatments must be presented to patients as a balance between a potentially beneficial tumour response and unwanted cytotoxic effects. Studies of dose intensification of cytotoxic drugs suggest higher rates of response but only a minor improvement in survival. The logical extension of these observations is the application of very high doses of cytotoxic drugs followed by bone marrow rescue, in an attempt to achieve maximum tumour control. Initial results indicate high rates of response, but the ultimate worth of these treatments awaits further evaluation and their use should be confined to assessment in randomised controlled trials. Alternative approaches include constant infusional chemotherapy, such as fluorouracil given over many weeks, often with low toxicity. Newer agents such as taxol have been extensively researched and are likely to be approved for second or third line treatments. The sensitivity of metastatic breast cancer to both cytotoxic and hormonal treatments and their different mechanisms of action make combined treatments attractive. However, the results of a trial comparing sequential and concurrent administration of tamoxifen and cytotoxic drugs (doxorubicin and cyclophosphamide) failed to demonstrate better survival with combined modality treatment.17 One Australian study comparing standard (continuous) and less intensive (intermittent course) cytotoxic drug treatment showed that the control of symptoms and quality of life were superior in the group receiving continuous chemotherapy, with a longer time to progression of cancer and better survival in this group.18 A follow-up study evaluating the physician's assessment of quality of life showed that those patients assessed as having better quality of life at the time of entry into the study also had better survival.19 It remains to be determined at what point dose intensity and better survival in metastatic breast cancer will be offset by unacceptable quality of life, and the study should not be interpreted as justifying the routine use of chemotherapy for advanced disease in the absence of defined symptoms. It is also possible that the patients receiving the more intensive treatment believed (despite information to the contrary) that they had a better chance of cure or remission. Patients' beliefs about treatment goals certainly require more research and understanding, for both standard and alternative therapies. Radiotherapy: Radiotherapy plays a major part in the palliation of a variety of localised symptoms. Box 6 lists the role of palliative radiotherapy, which can generally be given in one to five (daily) fractions, frequently on an outpatient basis, with the reasonable expectation of a significant impact on symptom control for most patients. A randomised study of bone pain palliation has confirmed that short courses are as effective and non-toxic as longer courses of two weeks or more.20 Complementary or alternative therapies Interventions such as massage, relaxation, aromatherapy, hypnotherapy, acupuncture and homoeopathy have gained widespread acceptance. The use of alternative therapies (such as naturopathy, nutritional, immunological or physical treatments) is also common, and may set the patient and clinician on a direct path of conflict which can be difficult to resolve. Consequently, many patients do not tell their clinicians that they are using them.21,22The need for patients to participate in decisions about treatment should be emphasised at all times. Doctors should recognise the limitations of modern oncological treatment, and be prepared to acknowledge the patient's need to explore other avenues. It is often helpful for doctors to offer to comment on this issue and such an offer is rarely rejected. There may be times when doctors feel that they must advise patients of a dangerous or futile treatment, with the occasional possibility of real harm being caused, and it should be pointed out that many therapies are completely untested. Sometimes it is helpful to differentiate between therapies which patients believe might cure them and those that help them to live more comfortably with their disease. Gentle exploration of patients' beliefs about potential curability of their disease may be important. Positive thinking strategies which obstruct appropriate care delivery for a dying patient may also need skilful addressing. Palliative care Modern palliative medicine offers a model of care which focuses on the whole person, within their social and emotional context. There is a difference between the adoption of a palliative approach and the delivery of holistic, multidisciplinary care appropriate to the individual patient's needs and wishes. It is not simply a matter of knowing when to stop oncological treatment, nor of a "cookbook" style of symptomatic management. The focus must be on the person rather than the disease, although a good knowledge of the natural history of the disease and relevant oncological practice is essential. Active oncological intervention is often required for malignant bone pain, fungating chest-wall disease or liver, lung or brain metastases, and can be of value until a very late stage in the disease process. About 10% of patients with metastatic breast cancer will develop symptomatic hypercalcaemia (symptoms include nausea, vomiting, polyuria, drowsiness) and should be treated with intravenous rehydration, diuretics and a bisphosphonate infusion. Pleural effusions may require aspiration if symptomatic. If they recur, pleurodesis with talc, tetracycline or BCG may be required for control of breathlessness. Meningitic carcinomatosis is very rare and may respond to intrathecal cytotoxic agents or craniospinal irradiation. It is important that the general practitioner be fully informed of the patient's management and condition. During a long disease course, often with multiple oncological events, it is all too easy (and understandable) for patients and families to become attached to a hospital oncology service and its staff. This may pose problems for palliative and terminal care at home, as a hitherto relatively uninvolved general practitioner may have to suddenly take over care. See Box 7 for definition of palliative care. Early referral to a specialised palliative care source should be considered for most patients with metastatic disease, to introduce future options in palliative care. Although sometimes confronting for patients and their oncological caring team, a commitment of future support and proper care planning is of real value in allowing patients to plan to live until they die. The general practitioner should be actively involved in this process of communication to ensure the smoothest possible transitions from curative to palliative and terminal care. In psychosocial support, emphasis is often required on issues of family history (anxieties about daughters developing the disease), body image and loss of femininity, although concerns about the latter may be less pronounced than at initial diagnosis. For younger women with children, death will leave the children without a mother, which is probably the hardest aspect for a woman to bear. Work on helping to hand over present and future parenting roles is required. The proper and appropriate use of opioid drugs is an essential skill for control of pain and shortness of breath. Nearly 30 years of safe international clinical experience has led the World Health Organization to recommend morphine as the opioid of first choice in cancer pain management.23 Other drugs (either alone or in combination with morphine) are usually required for deep somatic pain caused by bone metastases or liver capsule inflammation (non-steroidal anti-inflammatory drugs and corticosteroids), and neurogenic pain (antidepressants, anticonvulsants, membrane stabilising agents). Specialist help is nearly always required for neurogenic pain, often with the additional involvement of an anaesthetist with a special interest in cancer pain management. The regular oral administration of the right dose of an appropriate drug or drug combination is the cornerstone of modern cancer pain management. The dose of morphine is adjusted according to the patient's top-up (or "breakthrough") requirements. The management of cancer pain with morphine is somewhat unusual in that there is no absolute upper dose limit. Most patients will achieve initial pain control on an oral 24-hour morphine dose in the range of 100-200 mg, but there is very wide individual variation and if the dose continues to rise without response the cause of the pain and the drug choice should be reassessed. Advice about anticipated side effects and their prompt and effective management is essential, together with frequent review of pain control and analgesic dose. Intermittent subcutaneous injections or infusions may be used if the oral route is not possible (e.g., because of nausea and vomiting), or not effective. Shortness of breath, anxiety, acute delirium and so-called terminal restlessness may be managed with anxiolytic drugs such as diazepam, midazolam or clonazepam (after looking for a specific treatable underlying cause). Antiemetics also require regular administration in adequate doses, and may need to be used in combination (e.g., prochlorperazine 25 mg rectally 3-4 times daily with metoclopramide 30-90 mg per 24 hours by subcutaneous infusion). Bowel care is important (and often neglected) throughout the illness, but particularly towards the end of life. Most patients taking morphine will require a regular prophylactic aperient. Intensification of supports and symptomatic treatment will usually be required as death approaches, particularly if the patient and family have chosen for this to occur at home with the help of a domiciliary palliative care team (Box 8). Conclusion Doctors are being challenged to focus on the needs of the whole person and to work collaboratively with colleagues from other disciplines. Psychosocial support may be required from the time of diagnosis and should be an intrinsic part of caring throughout the course of the illness. It is also now widely accepted that there is more to the management of incurable disease than tumour regression alone, and therapeutic interventions need to be critically assessed on the basis of their impact on palliative endpoints, quality of life and psychological well-being. Acknowledgement We thank Dr Angela Rutherford, General Practitioner, East Brunswick Medical Centre, Victoria, for her comments and assistance. References Walker LG, Cordiner CM, Gilbert FJ, et al. How distressing is attendance for routine breast screening? Psycho-Oncology 1994; 3: 299-304. Fallowfield LJ, Hall A, Maguire GP, et al. Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial. BMJ 1990; 301: 575-580. Silberfarb PM, Maurer LH, Crouthamel CS. Psychological aspects of neoplastic disease: 1. Functional status of breast cancer patients during different treatment regimens. Am J Psychiatry 1980; 137: 450-455. Dean C. Psychiatric morbidity following mastectomy: preoperative predictors and types of illness. J Psychosom Res 1987; 31: 385-392. Bukberg J, Penman D, Holland JC. Depression in hospitalised cancer patients. Psychosom Med 1984; 46: 199-212. Maguire P. The repercussions of mastectomy on the family. Int J Fam Psychiat 1981; 6: 485-503. Kissane DW, Bloch S, Burns WI, et al. Perceptions of family functioning and cancer. Psycho-Oncology 1994; 3: 259-269. Massie MJ, Holland J, Glass E. Delirium in terminally ill cancer patients. Am J Psychiatry 1983; 140: 1048-1050. Endicott J. Measurement of depression in patients with cancer. Cancer 1984; 55: 2243-2248. Kissane DW, Bloch S, Burns WI, et al. Psychosocial morbidity in the families of patients with cancer. Psycho-Oncology 1994; 3: 47-56. Moorey S, Greer S. Psychological therapy for patients with cancer. A new approach. Oxford: Heinemann, 1989. Spiegel D, Bloom JR, Kraemer HC, et al. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 1989; 1: 888-891. Worden JW. Grief counselling and grief therapy. 2nd ed. New York: Springer, 1991. Fawzy FI, Fawzy NW, Hyun CS, et al. Effects of an early structured psychiatric invention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psychiatry 1993; 50: 681-689. Greer S, Morris T, Pettingale KW, et al. Psychological response to breast cancer and 15-year outcome. Lancet 1990; 335: 49-50. Mulder CL, Van der Pompe G, Spiegel D, et al. Do psychosocial factors influence the course of breast cancer? A review of recent literature, methodological problems and future directions. Psycho-Oncology 1992; 1: 155-167. ANZ Breast Cancer Trials Group. A randomised trial of post-menopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. J Clin Oncol 1982; 4: 186-193. Coates A, Gebski V, Bishop JF, et al. for the ANZ Breast Cancer Trials Group. Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. N Engl J Med 1987; 317: 1490-1495. Coates A, Gebski V, Signorini D, et al. for the ANZ Breast Cancer Trials Group. Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. J Clin Oncol 1992; 10: 1833-1838. Price P, Hoskin PJ, Easton D, et al. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 1986; 6: 247-255. Downer SM, Cody MM, McCluskey P, et al. Pursuit and practice of complementary therapies by cancer patients receiving conventional treatment. BMJ 1994; 309: 86-89. Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States. Prevalence, costs and patterns of use. N Engl J Med 1993; 328: 246-252. World Health Organization. Cancer pain relief. Geneva: WHO, 1986. Further reading and reference material Woodruff R. Palliative medicine. Symptomatic and supportive care for patients with advanced cancer and AIDS. Melbourne: Asperula, 1993. Raphael B. The anatomy of bereavement. A handbook for the caring professions. London: Routledge, 1984, reprinted 1990. Dunlop RJ, Hockley JM. Terminal care support teams. The hospital-hospice interface. Oxford: Oxford University Press, 1990. Buckman R. I don't know what to say. How to help and support someone who is dying. Sydney: Sun, 1990. Derek Doyle. Caring for a dying relative. A guide for families. Oxford: Oxford University Press, 1994. Doyle D, Hanks GWC, Macdonald N, editors. Oxford textbook of palliative medicine. Oxford: Oxford University Press, 1993. Trevelyan J, Booth B. Complementary medicine for nurses, midwives and health visitors. London: Macmillan, 1994. Spiegel D. Living beyond limits. New York: Times Books, 1993. Authors' details Palliative Care Centre, McCulloch House, Monash Medical Centre, Clayton, VIC. Michael A Ashby, FRCR, FRACP, Professor of Palliative Care, Department of Medicine, Monash University. Department of Psychiatry, Monash Medical Centre, Clayton, VIC. David W Kissane, FRACGP, FRANZCP, Senior Staff Specialist, and Senior Lecturer, Department of Psychological Medicine, Monash University. Wesley Medical Centre, Auchenflower, QLD. Geoffrey F Beadle, FRACP, FRACR, Medical Oncologist. William Buckland Radiotherapy Centre, The Alfred Health Care Group, Alfred Hospital, Prahran, VIC. Alan Rodger, FRCS, FRACR, Director and Professor, Department of Radiation Oncology, Monash University. No reprints will be available. Correspondence: Professor M A Ashby, McCulloch House, Monash Medical Centre, Clayton, Vic 3168. 1: Frequency of psychosocial problemsPsychosocial problemsPhase of illnessFrequencyGriefAll phasesUniversalAnxiety disordersMammography1 20%Diagnosis240%Adjuvant therapies233%Recurrence315%Palliative careCommonDepressive disordersMammography5%Diagnosis226%Adjuvant therapies4Minor 20%;major 5%Recurrence315% Palliative care542%Sexual disordersRemission/survival2 38%Family relationship problemsRemission633%Palliative care746% Back to text 2: Themes covered in psychological therapies for patients with breast cancer Multiple losses Death anxiety Fear of recurrence Living with uncertainty Understanding treatment regimens Body and self-image Sexuality Relationships with partner, family and doctors Surgical reconstruction Lifestyle review Future goals Back to text 3: Range of psychosocial supportsPsychotherapeutic techniqueIndicationsEarly stage group therapyGroup therapy is being assessed as an adjuvant to initial medical therapyAdvanced breast cancer group therapyDistress and poor coping; anxiety and depression; routine supportIndividual supportive psychotherapySymptomatic anxiety and depressionFamily therapyFamily distress and poor copingCouple therapyMarital and sexual difficultiesCommunity-based self-help groupsGeneral supportBack to text 4: Useful psychotropic agentsDepressiondothiepin75-300 mg at nightmianserin20-120 mg at nightsertraline50-200 mg dailyparoxetine20-40 mg dailymoclobemide150-900 mg divided into two daily dosesAnxietydiazepam2-40 mg divided into two or three daily dosesclonazepam0.5-8 mg divided into two daily dosesAgitation/deliriumhaloperidol1.5-10 mg divided into two or three daily dosesmidazolam1-5 mg single doses by intravenous injection, as required Back to text 5: Guidelines for selecting systemic treatmentInitial systemic treatmentEndocrine treatmentCytotoxic drug treatmentClinically indolent diseaseAggressive diseaseLong disease-free intervalShort disease-free intervalSlow progressionRapid progressionPositive tumour hormone receptor statusNegative tumour hormone receptor statusLow tumour bulk/few sitesHigh tumour bulk/many sitesSpecial site(s): bone marrow, liver, lung (lymphangitis carcinomatosa)Second and subsequent systemic treatmentsEndocrine treatmentCytotoxic drug treatmentPrior good response to endocrine treatmentProgression after first endocrine treatment requiring more intensive therapy Minimal or no response to previous endocrine treatments Good response to previous cytotoxic drugs Back to text 6: Indications for palliative radiotherapy Locoregional recurrence: ulceration, bleeding supraclavicular or axillary nodes Metastases:bone pain- localised: external beam localised fields- widespread: hemibody irradiationbase of skull/orbital diseaseimpending or pathological fractures- internal fixation and postoperative radiotherapybrain metastasescord compression- surgical decompression and stabilisation rarely indicatedmediastinal nodesBack to text 7: Definition of palliative care Hospice and palliative care is defined as a concept of care which provides coordinated medical, nursing and allied services for people who are terminally ill, delivered where possible in the environment of the person's choice, and which provides physical, psychological, emotional and spiritual support for patients and for patients' families and friends. The provision of hospice and palliative care services includes grief and bereavement support for the family and other carers during the life of the patient, and continuing after death. From: Australian Association for Hospice and Palliative Care Inc. Standards for Hospice and Palliative Care Provision, March 1994. Back to text 8: Clinical and practical issues in planning the palliative care of a person dying at home Pain and symptom control Place of care and death (home, hospice, hospital, nursing home) Role of the team members (who to call for help and when) Aids and equipment Distressing events (expected and unexpected, such as terminal confusion, vomiting or haemorrhage) The actual dying process (explaining to family how death usually occurs) What to do at time of death What to do after death (funeral arrangements, death certificates) Back to text

Michael A Ashby · David W Kissane · Geoffrey F Beadle · Alan Rodger

Editorial Shedding light on bowel cancer prevention The time has come for a concerted public education campaign MJA 1999; 170: 244-245 Colorectal cancer (CRC) is the second most common cause of cancer death in Australia.1 While motor vehicle accidents cause one death about every five hours, and breast cancer causes one death every four hours, CRC causes one every two hours. Australia has made a major government-sponsored effort to reduce mortality from motor vehicle accidents, and screening to prevent breast cancer mortality is an accepted government-sponsored initiative. Why then is there still confusion and argument about CRC prevention? There is convincing evidence that finding and removing adenomas in individuals at increased risk for bowel cancer prevents development of subsequent cancer in most.2 This would seem logical given the acceptance of the polyp-cancer sequence.3 In this issue of the Journal, Croese clearly demonstrates the potential for improving mortality.4 Using a community-based open-access colonoscopy service in Townsville, he showed that patients over 50 years of age who had undergone colonoscopy (with polypectomy when necessary) were less likely to be subsequently diagnosed with CRC than the remaining community in the same age group. Most of his repeat-colonoscopy patients had higher than average risk for developing CRC, which he defined as having one or more first-degree relatives with CRC or polyps, or ulcerative colitis, including quiescent pancolitis or active limited colitis. His message is simple: CRC can be prevented if those at increased risk are alerted to the need to enter a colonoscopic surveillance program. The strengths of the study are that it reports the outcome of "real world" colonoscopy practice from a relatively confined geographic area and provides details of cancers occurring during surveillance. The population was isolated, and the author was able to comprehensively cross-check data, making the information particularly valuable. The study's weaknesses -- a heterogeneous, unmatched population and retrospective comparisons -- were comprehensively addressed by the author. Although colonoscopic surveillance of those at higher risk of CRC is justified, surveillance intervals and starting age remain controversial. Timing of repeat colonoscopy will be partly influenced by the possibility of metachronous lesions, although these have been documented to occur in fewer than 1% of patients.5 The age at which to begin colonoscopic surveillance is also debated and, as about 8% of cancers develop in people aged under 50 years, it would not seem reasonable to withhold educational information from this group despite any perceived increase in cost. However, despite the simplicity of the message, many authorities in Australia still disagree on the need to deliver it. We need a coordinated, sponsored public education campaign to inform our community that an important step to reduce mortality from CRC is for those at increased risk (eg, first-degree relatives of people with CRC or polyps) to see a medical practitioner for advice and referral to an appropriate colonoscopic surveillance program. At the moment, the message is confused, as so well illustrated by Ward.6 Can we also shed some light on screening to prevent bowel cancer in the average-risk individual in our community? Setting aside the issue of mass screening for now and focusing on case-finding (ie, giving the appropriate advice to individuals who seek it or who may be receptive to it), there are four options for prevention or, at least, early diagnosis. Screening based on faecal occult blood testing (FOBT) reduces mortality from CRC. Studies showed a 16% reduction in mortality with biennial screening in the United Kingdom7 and Denmark,8 while a 33% reduction was seen with annual screening in the United States.9 Despite this well-designed research, the Australian Health Technology Advisory Committee has recently recommended further pilot studies on the efficacy of FOBT screening in the over-50 years age group. What other evidence they require remains a mystery. Flexible sigmoidoscopy is proposed for screening by many cancer authorities worldwide, usually in conjunction with FOBT. The combined approach recognises the limitations of flexible sigmoidoscopy, which may miss 50% of polyps and CRCs. Several retrospective studies have found that, in patients with proximal colon cancers, only 17%-30% of adenomas are in reach of the flexible sigmoidoscope.10 A prospective colonoscopy study showed that only 35% of 105 patients with proximal colon cancer had adenomas distal to the splenic flexure.11 These studies confirm that rectosigmoid adenomas ("sentinel" polyps) are an insensitive marker for proximal colon cancer, and that most proximal colonic neoplasms are not associated with distal polyps or cancer. These conclusions are supported by recent Australian data.12 Screening by flexible sigmoidoscopy alone would fail to detect 70%-80% of proximal cancers. Addition of annual FOBT would increase the diagnostic yield, but at increased cost. Colonoscopy is the third screening option, but has been criticised because of its cost and the failure to demonstrate that it improves mortality. Croese found that, in people aged over 50 years, the rate of cancer diagnosis in the unscreened population was double that in individuals who had previously had colonoscopy (for whatever reason). Almost half the cancers in the unscreened population were Dukes stage C or D, compared with only 16% in the previous-colonoscopy group.4 Australian data confirm that the cost-effectiveness of colonoscopy at both five- and 10-year intervals is almost identical to that of annual FOBT.13 Flexible sigmoidoscopy, alone or combined with FOBT, was found to be significantly less cost effective. Barium enema remains the fourth cost-effective diagnostic option, although it suffers from the fact that at least 20% of individuals will have a lesion identified which requires subsequent colonoscopy. A cohesive, unified and comprehensive public education campaign about CRC and the potential for its prevention is needed. This should emphasise the common nature of CRC and should target higher-risk groups, who can be offered colonic surveillance. This would be a start in reducing the current high mortality rate. When screening strategies for early diagnosis or prevention of CRC are chosen, compliance, costs and efficacy are all key issues. The fact that we have four effective options now allows the practitioner to offer individuals a menu from which they can select a test, depending on their preference and perceived compliance. Terry D Bolin Associate Professor, Gastrointestinal Unit Prince of Wales Hospital, Sydney, NSW Melvyn G Korman Associate Professor, Gastroenterology Unit Monash Medical Centre, Melbourne, VIC Anti-Cancer Council of Victoria. Canstat 1997; 26: 2. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993; 329: 1977-1981. Cotton S, Sharp L, Little J. The adenoma-carcinoma sequence and prospects for the prevention of colorectal neoplasia. Crit Rev Oncol 1996; 7: 293-342. Croese J. Colorectal cancer after open-access colonoscopy: a community and case survey. Med J Aust 1999; 170: 251-254. Leggett BA, Cornwell M, Thomas LR, et al. Characteristics of metachronous colorectal carcinoma occurring despite colonoscopic surveillance. Dis Colon Rectum 1997; 40: 603-608. Ward M. Preventing colon cancer: the problem with guidelines or The perils of prevention. Med J Aust 1997; 166: 201-204. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472-1477. Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348: 1467-1471. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328: 1365-1371. Lemmel GT, Haseman JH, Rex DK, Rahmani E. Neoplasia distal to the splenic flexure in patients with proximal colon cancer. Gastrointest Endosc 1996; 44: 109-111. Rex D, Chak A, Sack L, et al. Prospective determination of distal colon findings in patients with proximal colon cancer. Gastrointest Endosc 1998; 47: AB103. Nicholson FB, Stern AI, Korman MG, Hansky J. Colorectal cancer screening -- are proximal polyps missed by using flexible sigmoidoscopy? Digestion 1998 Suppl 3: 730. Bolin TD, Korman MG, Stanton R, et al. Positive cost effectiveness of early diagnosis of colorectal cancer. Colorectal Dis 1999; 1: 2. Reprints: Associate Professor T D Bolin, GI Unit, Prince of Wales Hospital, High Street, Randwick, NSW 2031. More articles on Gastroenterology Reprints: Associate Professor T D Bolin, GI Unit, Prince of Wales Hospital, High street, Randwick, NSW 2031. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Terry D Bolin · Melvyn G Korman

Research Colorectal cancer after open-access colonoscopy: a community and case survey John Croese MJA 1999; 170: 251-254 For editorial comment, see Bolin & Korman Abstract - Introduction - Methods - Results - Discussion - References - Author's Details - - More articles on Gastroenterology Abstract Objective: To evaluate whether colonoscopy protects against subsequent colorectal cancer (CRC). Design: Case and population survey. Setting: Townsville region in northern Queensland, between mid 1985 and January 1998. Subjects: All 8430 patients who underwent 11 148 colonoscopies performed by the author at the Mater Private Hospital (a community-based open-access colonoscopy service) between July 1985 and December 1996; those who were subsequently diagnosed with CRC, to January 1998; and all 476 residents diagnosed with colorectal cancer between 1994 and 1997. Main outcome measures: Age-standardised CRC incidence for 1994-1997 for patients who had had a previous colonoscopy and for the remaining community; Dukes' grade of CRCs. Results: For people aged 50 years and over, the incidence of CRC was significantly lower among those who had had a previous colonoscopy than in the remaining community (1.14 versus 2.31 per 1000 patient-years; P = 0.0046). For people aged 35-49 years, the incidence was 0.35 versus 0.31 per 1000 patient-years (P = 0.86). Thirty-one CRCs developed in 29 people who had had previous colonoscopy; only five of these CRCs were graded Dukes C, with none graded Dukes D. In contrast, almost half the CRCs in the rest of the community were graded Dukes C or D (P < 0.001). All but one of those diagnosed with CRC on repeat colonoscopy had risk factors (personal or family history), and 23 of the CRCs were subclinical, with 20 being diagnosed during surveillance colonoscopy. Conclusions: Patients aged over 50 years who had previously undergone a colonoscopy and ensuing treatment were less likely to be diagnosed with CRC than otherwise expected. Surveillance colonoscopy led to diagnosis of CRCs with lower Dukes grades. Introduction Colorectal cancer (CRC) is the most common internal malignancy and the second most common cause of death from cancer in Australia. CRC incidence in Australia is similar to that in other developed countries,1 but in the US both incidence and mortality are now decreasing.2 This change has been attributed to removal of premalignant polyps, detection of proportionally more early lesions by colonoscopy, and more effective treatment.3 Strategies based on colonoscopic surveillance and targeting people at increased risk of developing CRC are being promoted.3-5 However, colonoscopy, particularly in community-based, open-access practice, has not been shown to reduce CRC mortality. Indeed, although the rate of colonoscopies in Australia has increased fourfold since 1984, the incidence of CRC in New South Wales between 1973 to 1992 continued to increase by 2% per year in men and 0.9% per year in women.6This study aimed to evaluate whether colonoscopy protects against subsequent CRC by comparing CRC incidence and pathological grading between people who have had a previous colonoscopy and the rest of the population in a geographically isolated area. Methods Setting The study was set in Townsville and the surrounding region (defined by the postcodes 4804-4822, 4849 and 4850; Figure 1). Townsville is a regional centre in northern Queensland that provides centralised health services, including colonoscopy, for a population of 198 000 dispersed over 200 000 km2. The nearest alternative colonoscopy services are located at Cairns and Mackay, 400 km distant. Colonoscopy patients Subjects were patients who underwent colonoscopy performed by myself at the Mater Private Hospital, Townsville. All patients who underwent colonoscopy between July 1985 and December 1996 were identified, most from the hospital's detailed computerised records, but some of those examined between 1985 and 1990 from a hospital work ledger which gave only surname and given name. In addition, detailed demographic and clinical information was collected prospectively in a procedural database for all colonoscopy patients from April 1994 to December 1997. Similar information was obtained retrospectively from the case records of 600 randomly chosen patients who underwent colonoscopy between 1986 and 1990. Colonoscopic procedures and surveillance Colonoscopies were performed on patients referred by a general practitioner or specialist either for surveillance or for investigation of symptoms. Through concessions available until mid 1996, the service was equally available to all patients irrespective of financial resources. Fibreoptic colonoscopes were used before 1990, and video colonoscopes after then. Patients were lightly sedated with fentanyl (100 µg) and midazolam (2.5-5 mg). Treatment (eg, polypectomy, CRC resection) was given as necessary. Surveillance recommendations were mostly included in procedure reports and passed to both the patient and the referring doctor. While these recommendations changed over time consistent with published guidelines,3,7 a general summary is: Annual surveillance for either active ulcerative pancolitis of seven years' duration or longer or a previous malignancy plus a family history of hereditary non-polyposis colorectal cancer (HNPCC);3,7 One- to two-yearly surveillance for a previous CRC before 50 years and for those older than 25-40 years with either CRC developing in a first-degree relative before 50 years or a family history of HNPCC; Two- to five-yearly surveillance for longstanding quiescent pancolitis or active limited colitis, CRC or polyps in a first-degree relative, previous CRC, or large (>1 cm diameter) or multiple colonic polyps; and Five- to 10-yearly surveillance, depending on age, for a small adenomatous polyp. Colorectal cancer diagnoses All patients diagnosed with CRC in Townsville between January 1994 and December 1997 were identified retrospectively by searching the computerised databases of all three pathology services, three hospitals, three endoscopy services, three colonoscopists (including myself) and one oncology service provider in Townsville, and from the CRC audits maintained by the six surgeons in Townsville. From 1995, patients diagnosed with CRC were also identified prospectively by clinicians and institutions. Patients diagnosed with CRC who had had a previous colonoscopy performed by myself at the Mater Private Hospital were identified to January 1998. Clinical records of all patients diagnosed with CRC were audited by myself. A modified Dukes classification (A, B, C or D) was used for staging cancer spread.8,9 A malignant polyp was classified separately if colonoscopic resection was regarded as the definitive treatment. In cases of synchronous lesions, the lesion with the most invasive grading was registered. Incidence of CRC Colonoscopy population: The incidence of CRC was calculated as the number of cases per thousand patient-years for the period 1994-1997 for patients who had had a previous colonoscopy and still lived in the region in 1997 (colonoscopy population). Residence was determined from the electoral register current in January 1997,10 which is considered reliable as voter registration is compulsory in Australia. To reduce mismatch errors caused by individuals with identical names, only patients with a known middle name (duplication rate, 0.3%) were cross-referenced against voters who also had a recorded middle name (duplication rate, 1.3%). The number of patients without a middle name who were still resident was estimated and added to the above on the assumption that the proportion still resident would be the same in the groups with and without a known middle name. CRC incidence in each year was calculated for patients who had undergone previous colonoscopy up until the previous calendar year. For example, the incidence of CRC in 1994 was calculated for patients who had undergone previous colonoscopy up to 1993. Age of colonoscopy patients was determined for the year of incidence. The number of patient-years was the total for all patients in a given age range who had previously had a colonoscopy up to 1993, 1994, 1995 and 1996. Community: The incidence of CRC in the remaining population (community) was determined from the number of cases that occurred between 1994 and 1997 in people not registered as a colonoscopy patient per the region's population less the colonoscopy population. Population data were obtained from the August 1996 census undertaken by the Australian Bureau of Statistics.9 Statistical analyses Binary data were compared in two by two contingency tables using chi-squared analyses.12 The age-standardised incidences of CRC in colonoscopy patients versus the community were tested for the hypothesis that the ratios were equal to one.13 Results Colonoscopies From mid 1985 to the end of 1996, I performed 11 148 colonoscopies on 8430 patients (Figure 2). The number increased steadily, from 590 in the 18 months 1985-1986 to 2708 in the two years 1995-1996. The number of repeat colonoscopies increased from 12 (2.0%) in 1985-1986 to 875 (32.3%) in 1995-1996. Clinical and procedural characteristics are summarised in Box 1. Slightly more women than men had colonoscopies. Patients undergoing repeat colonoscopies were an average six years older than those newly referred and were more likely to have had surveillance for increased CRC risk as the primary indication (50.7% of repeat colonoscopies versus 15.0% of first colonoscopies; P < 0.0001). Primary indication also varied with time. For example, an abnormal barium enema was a common indication before 1991 (7.0%), but accounted for few after 1994 (0.3%; P < 0.0001). In contrast, a family history of polyps or CRC accounted for a greater proportion of colonoscopies after 1994 (10.6% of first and 11.2% of repeat colonoscopies) than before 1991 (6.3%; P < 0.0001). From the outset, the caecal completion rate exceeded 95%, and from 1994 it was 98.9% overall and 99.5% in those without a malignant obstruction. Polyps were diagnosed (and removed) in a greater proportion of repeat than first colonoscopies (36.1% versus 29.8%; P < 0.0001). Both these rates were higher than for colonoscopies performed before 1991 (24.5%; P < 0.0001). However, CRC was diagnosed less often in repeat than in first colonoscopies (0.6% versus 2.2%; P = 0.001). Resident populations Complete details, including a middle name, were recorded for 5762 of the 8430 colonoscopy patients (68.4%), and 4200 of these (72.9%) were registered voters and residents of the Townsville region in 1997. A surname and one given name only were recorded for the remaining 2668 patients -- 1913 from the hospital's computer register and 755 from the work ledger. This gave an estimated total number of resident colonoscopy patients of 6195 in 1997. Colorectal cancers Between 1994 and 1997, 476 new CRCs were diagnosed in residents of the Townsville region, with 474 in people aged over 35 years. Eighteen were in patients who had had a previous colonoscopy; each of these was diagnosed per colonoscopy by myself, nine at the study hospital (registered in the procedural database and shown in Box 1), and the remainder elsewhere. Incidences of CRC between 1994 and 1997 are shown in Box 2. In people aged over 50 years, the annual incidence of CRC in the colonoscopy population (1.14) was just less than half that in the remaining community (2.31; P = 0.0046). Between July 1985 and January 1998, I diagnosed 31 CRCs in 29 patients who had had a previous colonoscopy (two patients had a second CRC diagnosed two years after the first in each case). All but one of these patients had a personal or family history that warranted surveillance, and 21 had been enrolled in surveillance programs, with 20 (65%) having had multiple previous colonoscopies (mean, 3.4; range, 2-9). For 20 of the CRCs, planned surveillance was the indication for the repeat colonoscopy. Among the 11 people with symptoms as the primary indication, these symptoms were considered unrelated to the CRC in at least three. The time between most recent previous colonoscopy and diagnosis averaged 37 months (range, 3-136 months). Staging of CRCs is shown in Box 3. Metastatic spread from CRCs was less common in patients who had had a previous colonoscopy than in the community; only five of the 31 cases in colonoscopy patients were graded C, and none were graded D, while 219 of the 458 community cases (48%) were graded C or D (P < 0.001). Among the five colonoscopy patients with metastatic spread (Dukes C), the time between most recent previous colonoscopy and diagnosis was 19, 24, 29, 32 and 70 months, respectively. Discussion The study evaluated a colonoscopic service that followed and promoted contemporary surveillance guidelines similar to those currently recommended by professional cancer and gastroenterological societies.3 The incidence data suggest, but do not prove, that colonoscopic surveillance confers a benefit. Age-standardised incidence of CRC among people aged 50 years and over in the Townsville region was lower among those who had had a previous colonoscopy, along with any treatment considered necessary (eg, polypectomy or bowel resection), than in the community. This was despite the fact that many of those who had had a previous colonoscopy had a personal or family history likely to increase their risk of developing CRC. Furthermore, the CRCs that occurred in those who had had a previous colonoscopy were of a lower Dukes grade than those occurring in the community. The difference in incidence suggests but does not prove that colonoscopy is protective against CRC. CRC incidence for 1994-1997 in those who had had a previous colonoscopy may have been reduced, at least partly, by detection of subclinical CRCs during their pre-1994 colonoscopies. On the other hand, selection bias suggests that these people would develop more CRCs than the general population. The impact of each of these factors could not be measured, and there is no historical benchmark or matched population for comparison of outcomes. However, the result does suggest that colonoscopy confers a benefit, possibly because of removal of polyps and certainly because of detection and treatment of subclinical CRCs. In people aged 35-49 years, CRC incidence in those who had had a previous colonoscopy was similar to that in the community. Without a control group, a benefit of colonoscopy cannot be dismissed, as the colonoscopy group was expected to have higher CRC incidence. However, it is evident that, because of the large number of people aged 35 to 49 years and the low incidence of CRC, surveillance must be targeted to be effective. Polypectomy rate was high, and higher in repeat than in first colonoscopies. This also implies that patients having repeat colonoscopies had increased risk of developing CRC.14 While the high polyp rate may have been due to their older average age,15 the latter would also be expected to increase the CRC rate, which did not occur. Given an expectation that all lesions seen at the previous colonoscopy had been dealt with, this outcome (high polyp versus low CRC rate) validates the selection criteria for surveillance. The higher polypectomy rate after 1994 compared with that before 1990 probably relates to other circumstances, such as a higher caecal completion rate, while both indices probably reflect improved instrument technology. Thirty-one new primary cancers developed in 29 colonoscopy patients, with two-thirds diagnosed by planned surveillance colonoscopy. Metastatic spread occurred in only five of these patients. These findings confirm, firstly, that new CRCs will develop and, secondly, that outcome can be improved through early (subclinical) diagnosis.3,16 The number of cancers diagnosed in patients who had had a previous colonoscopy was of concern and suggested lesions might have been missed in the earlier examination. Colonoscopy, even when performed by an expert, does not identify all small lesions, while adverse conditions sometimes obscure gross pathology.17 Colon morphology, quality of the bowel preparation, instrument capabilities and operator proficiency may also impose limitations.3,18 However, substandard colonoscopy is unlikely to have been responsible. The caecum was reached at a rate exceeding the accepted standard (95%),3 and CRCs were observed in all parts of the bowel, arguing against an operator-dependent blind spot. Possibly, the comparatively large number of CRCs found in people undergoing colonoscopic surveillance was simply the outcome of increasing enlistment of an appropriate, at-risk cohort. Although most sporadic CRCs evolve slowly through malignant transition in a polyp, this sequence is truncated or absent for some sporadic CRCs and for CRCs developing in patients with ulcerative colitis or a genetic predisposition.19 It is unrealistic to imagine that surveillance colonoscopy with polypectomy as necessary will much reduce CRC incidence in such at-risk populations. Indeed, it might conceivably increase apparent incidence by uncovering subclinical CRCs. The results support the current practice of targeting individuals with recognised risk factors for surveillance colonoscopy. However, it is important to explain to patients that surveillance does not provide complete protection and that new CRCs are inevitable. Early diagnosis through repeated testing is the essential component of surveillance-derived protection. References Parkin DM, Pisani P, Ferlay J. Estimates of the world-wide incidence of eighteen major cancers in 1985. Int J Cancer 1993; 54: 594-606. SEER Program (National Cancer Institute). Surveillance, epidemiology, and end results (SEER) program. Bethesda, Md: National Cancer Institute, 1973-1992. Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; 112: 594-642. Bolin TD, Korman MG. How can we reduce the incidence and mortality of colorectal cancer [editorial]? Med J Aust 1997; 166: 175-176. Macrae FA. Screening for colorectal cancer, 1996 [editorial]. Med J Aust 1996; 165: 102-105. Bell JC, McCredie M, Coates MS, Armstrong BK. Trends in colorectal cancer incidence and mortality in New South Wales, 1973-1992. Med J Aust 1997; 166: 178-181. Mecklin J-P, Jarvinen HJ, Peltokallio P. Cancer family syndrome. Genetic analysis of 22 Finnish kindreds. Gastroenterology 1986; 90: 328-333. Astler VB, Coller FA. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann Surg 1954; 139: 846-851. Dunlop MG. Polyps and carcinoma. In: Shearman DJC, Finlayson N, Camillieri, Carter D, editors. Diseases of the gastrointestinal tract and liver. 3rd ed. New York: Churchill Livingstone, 1997: 1399-1448. Australian Electoral Commission. Elector information access system. Electoral roll information for Queensland. Canberra: Australian Electoral Commission, 1997. Australian Bureau of Statistics. 1996 census of population and housing. Community profile, Canberra: ABS, 1996 (Cat. no. 2020.0). Approximate significance for contingency tables. In: Matthews DE, Farewell VT. Using and understanding medical statistics. 2nd ed. Basel: Karger, 1988: 20-66. The binomial distribution. In: Snedecor GW, Cochran WG. Statistical methods. 8th ed. Ames: Iowa State University Press, 1989: 107-134. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992; 326: 658-662. Williams AR, Balasooriya BAW, Day DW. Polyps and cancer of the large bowel: a necropsy study in Liverpool. Gut 1982; 123: 835-842. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328: 1365-1371. (Published erratum appears in N Engl J Med 1993; 329: 672.) Rex RK, Cutler CS, Lemmel GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997; 112: 24-28. Baille J, Ravich WJ. On endoscopic training and procedural competence. Ann Intern Med 1993; 118: 73-74. Kuramoto S, Oohara T. Flat early cancers of the large intestine. Cancer 1989; 64: 950-955. (Received 1 May, accepted 21 Dec, 1998) Author's Details 42 Ross River Road, Townsville, QLD. John Croese, MD, FRACP, Gastroenterologist. Reprints will not be available from the author. Correspondence: Dr J Croese, 42 Ross River Road, Townsville, QLD 4812. Email: jcroeseATmedeserv.com.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> Back to text Back to text Back to text Back to text Back to text

John Croese

Editorial Confusion about secondary prevention for bowel cancer: resolving issues at the front line MJA 1999; 170: 102-103 An effective, clearly enunciated national policy is needed for secondary prevention (screening and surveillance) of bowel cancer in Australia. Bowel cancer meets the World Health Organization criteria for screening, and is the commonest internal malignancy affecting both sexes in Australia, causing more deaths than any other cancer except lung cancer.1Three randomised controlled trials have shown that screening average-risk populations (aged 50 years and over) by the crudest of faecal occult blood tests (Hemoccult) is effective in reducing population mortality from bowel cancer on an intention-to-screen basis.1 Furthermore, calculations of cost-effectiveness using Australian cost data and screening outcomes of the poorly specific rehydrated Hemoccult test show that screening for bowel cancer is about as cost effective as screening for breast cancer.2Given that neither mortality from bowel cancer nor cancer stage at diagnosis has improved in various Australian States,3 we can assume that current secondary prevention activities are only minimally effective. Indeed, the incidence of bowel cancer continues to rise in men.3 Why are we not conducting screening and surveillance? Why are we missing out on their demonstrable benefit? From a national perspective, two key issues arise: How should we implement screening to reduce population bowel cancer mortality rates?; and While this question is being answered, what is reasonable action for individuals interested in being screened or for those at risk of bowel cancer? Unfortunately, failure to separate these two issues has led to confusion and misunderstanding of promulgated guidelines. The issue of an effective population screening program was addressed in the Australian Health Technology Advisory Committee (AHTAC) report released in April 1998.1 A recent editorial in the Journal called for the issues raised in that report to be addressed and resolved.4 The AHTAC report proposed "pilot and feasibility studies" to examine aspects of screening, such as logistics, choice of screening tool, risks, costs, acceptability, resources and education. It took an evidence-based approach and considered the issues from a population perspective. Early in 1998, the National Cancer Control Initiative submitted a proposal to government seeking funds for pilot and feasibility studies in the general population. These funds have not yet been provided -- we will not have an effective program for the general population until results of pilot studies are available. In the meantime, doctors, and especially general practitioners (GPs), remain confused as to what is reasonable practice. Evidence for this confusion is presented by Sladden and Ward in this issue of the Journal.5 They found that many GPs are unaware of the evidence that screening is effective and are uncertain about intervals for testing, the age to start, and how to apply the screening/surveillance tools to an individual in a manner appropriate to the individual's risk profile. Few GPs are "highly likely" to recommend faecal occult blood screening (and presumably any other type of screening for bowel cancer) during a health check, even though we know that people who have biennial screening with Hemoccult have about a 40% reduction in risk of dying from bowel cancer.6Sladden and Ward point out that guidelines available in Australia are partly responsible for the confusion, because of their inconsistency in recommendations. This inconsistency arises partly because the issue is complex and the evidence is incomplete. Also, there is a failure to appreciate the difference in the guidelines between what is acceptable as a population strategy and what is reasonable for the individual who seeks screening. Given that the value of early-detection programs in average-risk individuals is supported by three randomised controlled trials of faecal occult blood test-based screening and by several case-control studies of flexible or rigid sigmoidoscopy screening, it is difficult to ignore the individual seeking help. The soon-to-be-promulgated Guidelines for the prevention, early detection and management of colorectal cancer of the National Health and Medical Research Council (NHMRC) and the Australian Cancer Network have been developed by a process of consensus, incorporating a national workshop and analysis of the evidence. These guidelines should provide a path through the confusion, provided they are endorsed and used by the medical colleges and other professional and educational bodies. They will also partly solve the problem of access to, and resourcing of, the colonoscopies needed for effective secondary prevention. Adherence to guidelines for colonoscopic surveillance of those at increased risk of bowel cancer might then free this limited resource for more effective deployment to a larger proportion of the population. The issues for the primary healthcare provider are complex: the GP needs to check the presence or absence of symptoms, profile the asymptomatic individual's risk, tailor the screening or surveillance program to that risk, and deal with the population's aversion to things anal or faecal. The media have been unhelpful in this respect, with little publicity given to bowel cancer.1,4 As pointed out by Sladden and Ward, GPs' actions might be suboptimal if they cannot immediately recall the necessary (rather complex) detail or access the services needed. When a GP considers that secondary prevention might be indicated, support in terms of education and access to carefully coordinated secondary prevention services should be provided by regional health services. The GP's role is important to the success of secondary prevention, whether it is part of a future coordinated mass program, or dealing with the individual seeking guidance or needing motivation. Clearer guidance will come from the NHMRC-Australian Cancer Network best practice guidelines. However, the continued rise in the incidence of bowel cancer and failure to lower its mortality will not be adequately controlled by such an ad hoc approach;7 population pilot studies are desperately needed, and so is government funding! Graeme P Young Professor of Gastroenterology, Flinders University of South Australia Head, Gastrointestinal Services, Flinders Medical Centre, and Repatriation General Hospital, Adelaide, SA Australian Health Technology Advisory Committee. Colorectal cancer screening. Canberra: Commonwealth Department of Health and Family Services, 1997. Salkeld S, Young G, Irwig L, et al. Cost-effectiveness analysis of screening by faecal occult blood testing for colorectal cancer in Australia. Aust J Public Health 1996; 20: 138-143. Bell JC, McCredie M, Coates MS, Armstrong B. Trends in colorectal cancer incidence and mortality in New South Wales 1973-1992. Med J Aust 1997; 166: 178-181. Collett JA, Olynyk JK. Colorectal cancer screening in average-risk, asymptomatic Australians [editorial]. Med J Aust 1998; 169: 14-15. Sladden MJ, Ward JE. Australian general practitioners' views and use of colorectal cancer screening tests. Med J Aust 1999; 170: 110-113. Hardcastle JD, Chamberlain JO, Robinson MHE, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472-1477. Neugut AI, Young GP. Screening for colorectal cancer: an overview. In: Young GP, Levin B, Rozen P, editors. Prevention and early detection of colorectal cancer. London: WB Saunders, 1996: 357-368. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Graeme P Young

Research Australian general practitioners' views and use of colorectal cancer screening tests Michael J Sladden and Jeanette E Ward MJA 1999; 170: 110-113 For editorial comment, see Young Abstract - Introduction - Method - Results - Discussion - Acknowledgements - References - Author's details - - More articles on Gastroenterology Abstract Objectives: To determine general practitioners' (GPs) current beliefs, knowledge and self-reported practices of screening for colorectal cancer. Design and setting: Postal survey of national random sample of 1271 GPs in 1996. Outcome measures: GP views on effectiveness of faecal occult blood testing (FOBT) and flexible sigmoidoscopy in reducing premature death from colorectal cancer in "average-risk" patients (asymptomatic with no family history); views on frequency of tests and target group; use of these tests; and independent predictors of views and use. Results: Response rate was 67%. FOBT and flexible sigmoidoscopy were said to be effective as screening tests by 38% and 61% of GPs, respectively, but 30% and 25% were unsure. Independent predictors of belief in screening effectiveness were State of practice (for FOBT), male sex and awareness of Gut Foundation guidelines (for flexible sigmoidoscopy) and increasing age (for both). Most often chosen screening frequencies were every year for FOBT (29%), and five-yearly for flexible sigmoidoscopy (24%), although 19% and 26%, respectively, were unsure of the appropriate screening interval. Most often cited target group was people aged over 40 years with first-degree relatives with colorectal cancer: 63% of GPs would offer FOBT and 74%, flexible sigmoidoscopy. Fewer than 3% of GPs were likely to adopt an opportunistic approach to screening, yet 15% would be highly likely to recommend FOBT during a dedicated health check-up for a 58-year-old male patient, and 9% for a female patient. Conclusion: The absence to date of a coherent national policy on colorectal cancer screening is associated with wide variations in views and practice that are inconsistent with the available evidence. If GPs are to be involved in implementing population screening, national policy must be widely and effectively promulgated. Introduction The past decade has seen a saga of unfinished policy initiatives on screening for colorectal cancer in Australia. As early as 1990, screening by faecal occult blood test (FOBT) was being promoted for people with "average risk" of colorectal cancer, in the absence of convincing evidence or national policy.1 Since then, a range of bodies have produced guidelines with quite different recommendations, particularly for this "average risk" group.2-8 Examples are shown in Box 1. More recent among these was the 1997 report of the Australian Health Technology Advisory Committee (AHTAC) Working Party on Colorectal Cancer Screening. This working party was formed after a 1994 call for a national symposium to develop "recommendations about early detection of colorectal cancer" as part of Australia's national health goals and targets,9 and a 1995 deputation to the Commonwealth from the Australian Cancer Network. The Network recommended pilot projects of screening and, if these were successful, implementation of national screening. AHTAC found that FOBT was effective in reducing mortality from colorectal cancer in the average-risk population (defined as the "well population aged over 50") and recommended studies to determine the effectiveness of different screening strategies, particularly how best to involve general practitioners (GPs). Meanwhile, in 1998, another set of draft guidelines, not yet nationally endorsed, was circulated by the Clinical Oncological Society of Australia and the Australian Cancer Network.8 Despite the unresolved status of national policy, research has continued to involve Australian GPs overtly or covertly in colorectal cancer screening.10-14 Most recently, a survey of Perth GPs reported high uptake of this screening.15 As no national studies have been conducted, we designed a postal survey to assess GPs' perceptions of the effectiveness of screening for colorectal cancer and self-reported levels of screening. Method GP sample and survey administration A covering letter, questionnaire and reply-paid envelope were mailed in May 1996 to a national random sample of 1271 GPs, as described elsewhere.16 Standardised response-aiding strategies were used to follow up non-respondents.16 Questionnaire Questions on colorectal cancer screening were part of a larger questionnaire on current status of cancer screening in general practice. Respondents were asked to tick the response that matched their views on: Effectiveness of FOBT and flexible sigmoidoscopy in reducing premature deaths from colorectal cancer in "average risk" patients (ie, asymptomatic patients with no family history); Frequency of screening; Who should be screened; Likelihood of their initiating a discussion about FOBT or flexible sigmoidoscopy with a well 58-year-old male, and next female, patient during non-urgent consultations for ear syringing as well as during scheduled health check-ups; and Usefulness of three guidelines available at the time of the surveys (first three items in Box 1). The final section of the questionnaire included eight sociodemographic questions. Data analysis Descriptive, cross-tabulation and logistic regression analyses were performed with SPSS for Windows 7.17 Logistic regression analyses were performed to determine independent predictors of knowledge and practice outcomes. Fourteen potential predictors were considered: GP's sex; age; State; full- or part-time practice; practice type (solo or group); membership of a Division of General Practice; Royal Australian College of General Practitioners (RACGP) affiliation; membership of the Australian Medical Association; personal history of cancer; family history of cancer; awareness of RACGP guidelines; Australian Gastroenterology Institute/Australian Cancer Society guidelines; and Gut Foundation of Australia (GFA) guidelines; and practice location (metropolitan or other18). All independent variables were included in the full model. A further variable -- belief that FOBT/flexible sigmoidoscopy is an effective screening test -- was included in the model to predict behaviour. A backwards stepwise modelling strategy was used to identify significant independent variables, whereby all dependent variables were initially included and non-significant terms were progressively eliminated. Significance was assessed using the Wald chi-squared statistic. Results We received 855 usable questionnaires from 1271 eligible GPs (67% response rate). The response rate for women (75%) was significantly higher than that for men (63%) (chi-squared = 15.4, 1 df, P < 0.001), but did not vary with age, vocational registration status, RACGP affiliation, or practice size and location. GP views about screening GP views about the effectiveness of screening for colorectal cancer in preventing premature deaths are shown in Box 2. More GPs believed flexible sigmoidoscopy to be effective (61%) than believed FOBT to be effective (38%), but there was substantial uncertainty about both screening tests, with 25% and 30% of GPs unsure. Independent predictors of believing either test to be effective are summarised in Figure 1. For FOBT, these comprised increasing GP age and State of practice (specifically, South Australia). For flexible sigmoidoscopy, they comprised increasing GP age, male sex, and awareness of the Gut Foundation guidelines (which favour screening). GPs' views on appropriate screening frequencies and target groups are shown in Box 2. Most often chosen frequencies were every year for FOBT (29%), and five-yearly for flexible sigmoidoscopy (24%). However, 19% and 26%, respectively, were unsure of the appropriate screening interval. The most often cited target group was people aged over 40 years with first-degree relatives with colorectal cancer: 63% of GPs would offer FOBT and 74%, flexible sigmoidoscopy. Self-reported practice Likelihood of suggesting colorectal cancer screening is shown in Box 3. Fewer than 3% of GPs were "highly likely" to adopt an opportunistic approach to colorectal cancer screening for a 58-year-old patient (by either test) or to recommend flexible sigmoidoscopy screening during a dedicated health check-up. More would be "highly likely" to recommend FOBT during a dedicated health check -- 15% if the patient was a man and 9% if a woman. This sex difference was significant (McNemar's chi-squared = 43.7, 1 df, P < 0.0001). Independent predictors of being "highly likely" to include FOBT in a health check-up are shown in Figure 2. They comprised increasing GP age, State of practice, and belief in the effectiveness of the tests. Usefulness ratings of guidelines available at the time of the survey are shown in Box 4. While RACGP, AGI/ACS and GFA guidelines were rated as "very" or "somewhat" useful by 33%, 50% and 45% of respondents, respectively, they were unable to be recalled by 52%, 35% and 41%. Discussion Our study suggests considerable confusion about colorectal cancer screening at the "front line" of general practice. About a third of respondents believed that FOBT was an effective screening test in average-risk individuals, while two-thirds believed this of flexible sigmoidoscopy. These beliefs are inconsistent with the evidence available at the time of our study: level II (randomised controlled trial) evidence19 that FOBT reduced colorectal cancer mortality, but only level III (case-control study) evidence20 supporting flexible sigmoidoscopy. A wide range of responses were given about appropriate screening frequency. This is not surprising, as the three guidelines available at the time offered different and contradictory advice, and none met the criteria for being systematically evidence-based. Further confusion is likely if yet more guidelines8 are published that contradict the evidence-based AHTAC guidelines.7Far fewer GPs reported using the screening tests than reported they were effective; most respondents did not use the tests. This discordance was greater for sigmoidoscopy than for FOBT. Again, it is likely that the lack of clarity and the variation between guidelines, as well as availability of conflicting information and educational material, have caused uncertainty among GPs, with concomitant inconsistency in their behaviour. Perhaps FOBT is used more often than sigmoidoscopy because it is easier to arrange. Increasing GP age and physician belief in screening effectiveness independently predicted self-reported provision of screening. South Australian GPs were more likely to advocate screening, perhaps because of research studies and community-based initiatives in that State.10 GPs also favoured screening men rather than women for colorectal cancer. Sex bias not been reported previously in colorectal cancer screening, and may reflect the higher incidence of colorectal cancer among men.21 Alternatively, perhaps GPs place a lower priority on colorectal cancer screening in women, for whom cervical and breast cancer screening are widely performed, but a higher priority in men, for whom there is, as yet, no "male cancer" screening of proven benefit. National levels of self-reported use of screening tests were less than previously reported,15,22,23 although the higher levels in South Australia were consistent with earlier data.10 GPs' wider endorsement of screening for "above-average-risk" individuals with first-degree relatives with colorectal cancer (63%-74%) was similar to the levels found in recent studies (80%-94% GP support),10,15 but considerably higher than in a similar 1982 study (23% GP support).22 Screening of relatives is apparently becoming more acceptable. Usefulness and recall of guidelines was low, similar to other recent findings.15 Our results suggest an urgent need for a national colorectal cancer screening policy. As GPs remain the most respected source of health information,24 it is vital they have access to timely and accurate information. The AHTAC report, released in 1998, was necessary but insufficient. If GPs are to be involved in implementation of colorectal cancer population screening (which, by definition, will target average-risk individuals), strategies are needed to inform them of the importance of screening and to facilitate appropriate changes in behaviour. When there has been a concerted effort to communicate agreed policy to Australian GPs (eg, about mammographic screening), uniformity of GP views has been achieved.25 However, when evidence is lacking (eg, for clinical breast examination),25 or State-based initiatives are patchy,26 it appears that GPs differ considerably in their views of screening effectiveness and self-reported behaviour. Our study concentrated on screening average-risk individuals, for which previous guidelines have been confusing, non-evidence based and at variance with each other. Most guidelines distinguish between screening for average-risk and above-average-risk individuals, generally recommending colonoscopic screening for above-average-risk groups (eg, those with familial adenomatous polyposis and hereditary non-polyposis colorectal cancer). Clearly, strategies for effective evidence-based screening of above-average-risk groups must also be promoted. Thus, our results reveal our failings to date as an organised healthcare system to provide GPs with timely, consistent and evidence-based health policy, as they and their patients deserve. Our study provides a baseline against which the effectiveness of future dissemination of colorectal cancer screening policy may be measured. Acknowledgements A Commonwealth General Practice Evaluation Program seeding grant funded this study. We thank the GPs who participated in our research with no financial incentive, Phoebe Holt for contributing to questionnaire design, and Tracey Bruce for diligent survey administration. The study was approved by the Ethics Committee of the Royal Prince Alfred Hospital, Sydney, NSW. References Woodward A, Weller D. Colorectal cancer: implications of mass screening for public health. Med J Aust 1990; 153: 81-88. Guidelines for screening for colorectal cancer. Sydney: Australian Gastroenterology Institute, 1991. Australian Cancer Society. National cancer prevention policy, 1993. Sydney: Australian Cancer Society, 1993. Bolin T, Collopy B, Cowen A, et al. Colorectal cancer: prevention, diagnosis and treatment. Sydney: The Gut Foundation and Colorectal Surgical Society of Australia, 1993. Goulston K, St John DJ, Bokey L, et al. Guidelines for early detection, screening and surveillance for colorectal cancer. 2nd ed. Sydney: Australian Gastroenterology Institute and Australian Cancer Society, 1994. Guidelines for preventive activities in general practice. 3rd ed. Sydney: Royal Australian College of General Practitioners, 1994. Australian Health Technology Advisory Committee (Standing Committee of the National Health and Medical Research Council). Colorectal cancer screening. Canberra: Commonwealth Department of Health and Family Services, 1997. Clinical Oncological Society of Australia and Australian Cancer Network. Guidelines for the prevention, early detection and management of colorectal cancer. Draft 3. June 1998. Better health outcomes for Australians. Canberra: National Health Goals and Targets Section, Department of Human Services and Health, 1994. Cockburn J, Thomas R, McLaughlin S, et al. Acceptance of screening for colorectal cancer by flexible sigmoidoscopy. J Med Screen 1995; 2: 79-83. Rae L. Community screening for colorectal cancer in north-eastern New South Wales, 1987-1996. Med J Aust 1998; 168: 382-385. King J, Fairbrother G, Thompson C, Morris D. Colorectal cancer screening: optimal compliance with postal faecal occult blood test. Aust N Z J Surg 1992; 62: 714-719. King J, Fairbrother G, Thompson C, Morris D. Influence of socioeconomic status, ethnicity and an educational brochure on compliance with a postal faecal occult blood test. Aust N Z J Public Health 1994; 18: 87-92. Olynyk J, Aquilia S, Fletcher D, Dickinson J. Flexible sigmoidoscopy screening for colorectal cancer in average-risk subjects: a community-based pilot project. Med J Aust 1996; 165: 74-76. Olynyk J, Aquilia S, Platell C, et al. Colorectal cancer screening by general practitioners: comparison with national guidelines. Med J Aust 1998; 168: 331-334. Ward J, Bruce T, Holt P, et al. Labour-saving strategies to increase response rates in general practice surveys. Aust N Z J Public Health 1998; 22: 394-396. Statistical Package for the Social Sciences. SPSS for Windows 7.5.1. Chicago (Ill): SPSS Inc, 1996. Commonwealth Department of Primary Industries and Energy and Commonwealth Department of Human Services and Health. Rural, Remote and Metropolitan Areas Classification: 1991 Census edition. AGPS, Canberra: 1994. Mandel J, Bond J, Church T, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993; 328: 1365-1371. Selby J, Friedman G, Quesenberry C, Weiss N. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326: 653-657. Jelfs P, Coates M, Giles G, et al. 1996 Cancer in Australia 1989-1990 (with projections to 1995). Canberra: Australian Institute of Health and Welfare (Cancer Series No. 5). Macrae FA, Hill DJ, Dent O, et al. Colorectal cancer: knowledge and attitudes of doctors in Victoria. Aust N Z J Med 1982; 12: 278-283. Rolfe I, Pearson S. Screening recommendations in general practice: a survey of graduates from different medical schools. Med J Aust 1996; 165: 14-17. Cumming R, Barton G, Fahey P, et al. Medical practitioners and health promotion: results from a community survey in Sydney's western suburbs. Community Health Stud 1989; 13: 294-301. Young J, Ward J, Holt P. Breast cancer screening in Australian general practice: results of a national survey. Med J Aust 1998; 169: 364-368. Ward J, Donnelly N, Holt P. Impact in general practice of the policies of the organised approach to preventing cancer of the cervix. Aust N Z J Public Health 1998; 22: 336-341. (Received 25 Jun, accepted 28 Oct, 1998) Author's details Division of Community and Rural Health, University of Tasmania, Hobart, TAS. Michael J Sladden,FRACGP, MAppEpid, Honorary Senior Lecturer. Needs Assessment and Health Outcomes Unit, Central Sydney Area Health Service, Sydney, NSW. Jeanette E Ward, PhD, FAFPHM, Director. Reprints will not be available from the authors. Correspondence: Dr M J Sladden, Division of Community and Rural Health, PO Box 252-33, University of Tasmania, Hobart, TAS 7001. Email: M. Sladden@utas.edu.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> Figure 1 : Independent predictors of general practitioners (GPs) reporting that faecal occult blood testing or flexible sigmoidoscopy is effective in reducing premature deaths from colorectal cancer. Back to text Figure 2 : Independent predictors of general practioners (GPs) reporting they would be "highly likely" to discuss faecal occult blood testing during a deicated health check-up with a 58-year-old patient. (Adjusted odds ratios with 95% confidence intervals are available from the authors.)Back to text 1: Recommendations about colorectal cancer screening for average-risk* people Gut Foundation of Australia (1993)4 Screening by annual FOBT; consider 3-5-yearly flexible sigmoidoscopy Australian Gastroenterology Institute/Australian Cancer Society (1994) 5 Routine screening not recommended; can be performed at patient request Royal Australian College of General Practitioners (1994)6 Screening not recommended Australian Health Technology Advisory Committee (1997)7 Screening by FOBT; research required to determine method and frequency Clinical Oncological Society of Australia/Australian Cancer Network (draft 1998)8 Screening by annual FOBT; consider 5-yearly flexible sigmoidoscopy FOBT=faecal occult blood test. *Asymptomatic people aged over 50 years with no family history Back to text Back to text Back to text Back to text

Michael J Sladden · Jeanette E Ward

Editorial Cancer immunotherapy: new leads on an elusive goal Emerging data increase optimism for mobilising immune cells against cancer MJA 1998; 169: 570-571 The prospect of mobilising the body's immune defences against cancer cells has been an elusive goal in cancer therapy for many decades. The optimism held for this idea has fluctuated over the years, but there are now concrete data emerging from a number of fronts that give good reason to be optimistic about cancer immunotherapy in the medium term. The new data on prospects for cancer immunotherapy were brought together at a recent meeting in Canberra.* Australia has outstanding researchers in this field, and this meeting was an opportunity to assess the current hopes and limitations from multiple perspectives. One chief limitation to cancer immunotherapy has been the difficulty in finding good, cancer-cell-specific target antigens. Immunological tolerance to self antigens on healthy tissues has mistakenly been thought of as an absolute process, barring the prospect of ever getting immune cells to react against cancer cells unless antigens unique to the cancer could be found. Two new developments dispel this perceived limitation. Firstly, many of the cellular processes responsible for immunological self-tolerance are at last being illuminated, through new technologies to genetically engineer transgenic mice.1-4 Definitive work on the process of tolerance to tissue-specific antigens was presented by B Scott (University of Western Australia, Perth), W Heath (Walter and Eliza Hall Institute, Melbourne), F Alderuccio (Monash University Medical School, Melbourne), D Hanahan (University of California, San Francisco) and myself. The data show that tolerance to tissue-restricted antigens, such as proteins made only by specific epithelial, neuronal or endocrine cells, is acquired by regulatory processes that still allow circulation of T cells and B cells with tissue-reactive antigen receptors. If these regulatory processes can be defined and temporarily relaxed by specific drug antagonists, this potential reservoir of immune cells might, in principle, be called into action to destroy cancer micrometastases. One potential target for such antagonists is suggested by inherited mutations in a novel gene, Autoimmune Regulator (AIRE); mutations of AIRE cause a failure of tolerance to multiple endocrine tissues in patients with autoimmune polyendocrinopathy- candidiasis syndrome (N Shimizu, Keio University). Conversely, a potential immune agonist is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a potent inducer of immunity and appears essential for destructive autoimmunity in experimental diabetes mellitus (T Kay, Walter and Eliza Hall Institute, Melbourne). Notionally, such an immunotherapeutic course would follow after a primary tumour is surgically resected or debulked by radiotherapy or chemotherapy. The second development that opens the field of cancer antigen targets is coming from a clinical serum analysis technique called SEREX, which shows that tumours induce "autoimmune responses" much more frequently than has been appreciated.5,6 Autoantibodies against neuromuscular receptors have long been known to cause paraneoplastic syndromes of myasthenia gravis and Lambert-Eaton syndrome in patients with specific types of tumours such as thymoma or small cell lung carcinoma. Results obtained using SEREX show that patients who have any of a broad range of tumours are often making autoantibodies against various tissue-restricted antigens carried by the tumour cells (J Cebon, Ludwig Intitute, Melbourne; B Robinson, University of Western Australia, Perth). These results make it likely that immune defences can be mobilised against many tumours, but how effective will this be and how can they be improved? J Cebon summarised data suggesting that some patients with high antibody responses to tumours survive somewhat longer, but it is still uncertain that immune surveillance is a factor even in these cases, and it is clear that, ultimately, the tumour exceeds or escapes any immune surveillance.5 Genetically engineered mouse models of pancreatic cancer or skin cancer display spontaneous immune responses to cancer antigens,7,8 but augmenting these immune responses only delays tumour progression,9 and the extent to which the spontaneous immune responses restrict tumour growth appears quite limited (D Hanahan and D Daniel, University of California, San Francisco; C Parish, John Curtin School of Medical Research, Canberra). A review of individual case studies provides provocative examples of patients where squamous cell carcinomas or melanomas have spontaneously regressed, accompanied by vigorous immune cell responses to the tumour (G Halliday, University of Sydney).10 The potential for immune control of cancer cells is best illustrated by cancers of viral origin and by organ-specific autoimmune diseases. Only a small proportion of people infected with Epstein-Barr virus or human papillomavirus 16 develop lymphoma or cervical cancer, and there is clear evidence that this is due partly to effective immune responses against the viral antigens carried by the tumour cells (R Khanna, Queensland Institute of Medical Research, Brisbane; I Frazer, Princess Alexandra Hospital, Brisbane).8,11 The devastating destruction of pancreatic islet beta cells in type 1 diabetes mellitus, where no virus is known to be involved, is testimony that immune defences can be unleashed against common tissue antigens as well. Why do most tumours not remit despite ongoing immune responses? Several factors were clearly indicated at the meeting. Firstly, K Lafferty (John Curtin School of Medical Research, Canberra) reviewed recent studies in diabetes showing that vigorous immune responses can be "benign" (non-destructive) or "malignant" (destructive).12 Islet tissues can be heavily inflamed by a benign autoimmune response without any damage to beta cell mass because of poorly understood regulatory processes for self-tolerance.1,3,4 Genetic predisposition only allows a switch to malignant inflammation in certain individuals. As discussed above, the solution to this problem lies in charting the molecular pathways regulating tolerance and developing specific ways to interfere with them transiently. Secondly, tumour cells are genetically unstable and constantly evolving. In viral tumours, cancer cells escape immune surveillance by losing antigens or by losing the machinery needed to present antigens to T cells.11 Tumour instability is a serious problem for any single therapeutic approach, as it is for radiotherapy or chemotherapy, and successful application of immunotherapy will probably also depend on the tumour type and tailored combination with other measures. Thirdly, D Hanahan, B Robinson, G Halliday, and C Parish each drew attention to fragmentary evidence that secreted products from tumours -- such as activins -- and tumour influences on local vasculature and extracellular matrix may create suppressive or non-permissive environments for immune responses.13 It is conceivable that some of these products, such as transforming growth factor b, are key elements of normal mechanisms to prevent organ-specific autoimmunity. This is the least understood of all the obstacles facing immunotherapy. Counteracting such tumour products should not be an insurmountable barrier, but it may take considerable time and effort to define the molecular pathways involved and develop small-molecule antagonists against the best targets. Christopher C Goodnow Professor, Australian Cancer Research Foundation Genetics Laboratory Medical Genome Centre, John Curtin School of Medical Research The Australian National University, ACT Scott B, Liblau R, Degermann S, et al. A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. Immunity 1994; 1: 73-83. Heath WR, Kurts C, Miller JF, Carbone FR. Cross-tolerance: a pathway for inducing tolerance to peripheral tissue antigens. J Exp Med 1998; 187: 1549-1553. Forster I, Hirose R, Arbeit JM, et al. Limited capacity for tolerization of CD4+ T cells specific for a pancreatic beta cell neo-antigen. Immunity 1995; 2: 573-585. Akkaraju S, Ho WY, Leong D, et al. A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis. Immunity 1997; 7: 255-271. Old LJ, Chen YT. New paths in human cancer serology. J Exp Med 1998; 187: 1163-1167. Robinson C, Robinson BW, Lake RA. Sera from patients with malignant mesothelioma can contain autoantibodies. Lung Cancer 1998; 20: 175-184. Skowronski J, Jolicoeur C, Alpert S, Hanahan D. Determinants of the B-cell response against a transgenic autoantigen. Proc Natl Acad Sci U S A 1990; 87: 7487-7491. Frazer IH. Immunology of papillomavirus infection. Curr Opin Immunol 1996; 8: 484-491. Ye X, McCarrick J, Jewett L, Knowles BB. Timely immunization subverts the development of peripheral nonresponsiveness and suppresses tumor development in simian virus 40 tumor antigen-transgenic mice. Proc Natl Acad Sci U S A 1994; 91: 3916-3920. Halliday GM, Patel A, Hunt MJ, et al. Spontaneous regression of human melanoma/nonmelanoma skin cancer: association with infiltrating CD4+ T cells. World J Surg 1995; 19: 352-358. Khanna R, Burrows SR, Moss DJ. Immune regulation in Epstein-Barr virus-associated diseases. Microbiol Rev 1995; 59: 387-405. Gazda LS, Charlton B, Lafferty KJ. Diabetes results from a late change in the autoimmune response of NOD mice. J Autoimmun 1997; 10: 261-270. Jarnicki AG, Fitzpatrick DR, Robinson BW, Bielefeldt-Ohmann H. Altered CD3 chain and cytokine gene expression in tumor infiltrating T lymphocytes during the development of mesothelioma. Cancer Lett 1996; 103: 1-9. * Autoimmunity workshop: the interface between autoimmunity and cancer immunity, sponsored by the John Curtin School of Medical Research, Australian National University. 11-13 September 1998. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Christopher C Goodnow

Melanoma in the elderly -- a neglected public health challenge Successful strategies for early detection in the young are not benefiting older people MJA 1998; 169: 403-404 Melanoma has long been recognised in Australia for its relatively high incidence in young adults, compared with other cancers, and its significant contribution to premature mortality.1,2 Twenty-five years ago it was recognised that many melanomas begin with a flat, superficial growth pattern and the term "radial growth phase" was coined by the late Wallace Clark.3 Diagnostic criteria were adjusted to direct attention to flat lesions with what are known as "ABCD" features (Asymmetry, Border irregularity, Colour variation and large Diameter) and away from raised, nodular lesions. This promoted the early detection of radial growth phase melanomas (superficial spreading, lentigo maligna and acral lentiginous melanomas) and has been associated with a progressive decline in tumour thickness and a corresponding improvement in prognosis. Further, benchmark public education campaigns such as the Anti-Cancer Council of Victoria's Sunsmart program have contributed to significant changes in behaviour aimed at primary prevention.4 The new and recently demonstrated decline in melanoma incidence among people under 35 years of age5 may be a result of these behavioural changes. These, then, are among the success stories in the fight against melanoma. But where are we failing? In this issue of the Journal Hanrahan et al direct our attention to a group that appears to have been bypassed by the advances -- elderly men.6 The elderly comprise an important group among those affected with melanoma. The age-specific incidence of melanoma continues to rise throughout life, most steeply in men.1 While incidence rates have levelled off or are falling in younger age groups, they continue to rise steeply in the elderly.5 However, it is not incidence, but mortality, that most strongly conveys the predicament of the elderly in our population with respect to melanoma. Mortality from melanoma for Australian men aged between 80 and 84 years is 10 times that of those aged between 40 and 44 years (48.16 v. 4.92 per 100 000 person-years).7 As Hanrahan and colleagues point out, some 50% of deaths from melanoma in New South Wales occur in males over 50 years, even though this group accounts for only 12%-14% of the population. In light of this high mortality, and with tumour thickness being the most important prognostic indicator, as might be expected, tumours diagnosed in the elderly are thicker at the time of diagnosis.8 Why have the elderly so comprehensively failed to follow the trend toward early detection of melanoma that has been shown in younger members of the community? Obviously, they may be disadvantaged by age-related handicaps, such as failing eyesight, loss of a partner and the development of numerous seborrhoeic keratoses that may appear similar to melanoma. Surprisingly, however, the work of Hanrahan et al suggests that it is not primarily these difficulties, but the greater proportion of nodular melanoma compared with superficial spreading melanoma (particularly in men), that inhibits early detection of melanoma in the elderly. The direction of attention to flat lesions, while greatly improving the detection of those tumours that are easiest to detect early, has ignored the problem of early detection of nodular melanomas (which exhibit only vertical growth and have no radial growth phase). An additional difficulty for elderly men is that their melanomas occur predominantly on the back (48%). Hanrahan and colleagues found that once tumour type, site and thickness, and age were taken into account, men were no less likely than women to detect their melanomas. While people aged 50 years or over were somewhat less likely than younger people to identify the changes of melanoma (62% v. 72%), Hanrahan et al have demonstrated in a related study that older people are no less able to identify the changes of early melanoma in computer-altered images of pigmented lesions.9 These findings suggest that the elderly are not making use of their skills in detecting melanomas, and that public education campaigns might usefully encourage them to do this. Where have we gone wrong for the elderly with melanoma? By directing public education about primary prevention at the young we have also generated early detection behaviour primarily in this group. Marks et al10 and Del Mar et al11 have drawn attention to the mismatch between the age at which pigmented lesions are being excised, and the later age at which melanoma is more likely to occur. Among people aged 21-40 years the ratio of benign naevi to melanomas among excised lesions was 27.2, compared with 1.4 in those aged 60 and over.10 By focusing early detection efforts on flat lesions we have distracted attention from the clinical features of the nodular melanomas that more frequently affect the elderly. Nodular melanoma is, of course, more difficult to detect in its early stages because these lesions are invasive from the outset and grow in both depth and diameter, while the invasive, vertical growth phase of other melanomas is preceded by a flat, radial growth phase that may last many months or years. However, my own clinical experience suggests that it is generally possible to diagnose nodular melanoma lesions in patients undergoing regular surveillance when they are about 1.0 mm in thickness. We must make the elderly aware that melanoma is a significant and potentially curable health problem in later life. Further research is needed to define the most useful clinical features for early detection of nodular melanoma and to explore the best methods of promoting earlier detection. The article by Hanrahan et al in this issue provides some clues: changes in colour are found less frequently and changes in sensation more frequently in nodular melanomas; bleeding is associated with thick melanoma and is therefore not useful in early detection. Healthcare practitioners who work with the elderly need to be particularly aware of the clinical features of nodular melanoma, and the role of opportunistic screening by general practitioners is of special importance for elderly men in view of the greater impediments to self- diagnosis (nodular melanomas and location on the back). This role needs emphasis in the education of general practitioners. John W Kelly Head, Victorian Melanoma Service, Head, Dermatology Unit, and Clinical Associate Professor, Monash University Department of Medicine, Alfred Hospital, Melbourne, VIC Jelfs PL, Giles G, Shugg D, et. al. Cutaneous malignant melanoma in Australia, 1989. Med J Aust 1994; 161: 182-187. Gold J, Yuerning L, Kaldor JM. Premature mortality in Australia 1983-1992, the first decade of the AIDS epidemic. Med J Aust 1994; 161: 652-656. Clark WH, Ainsworth AM, Bernadino EA, et al. The developmental biology of primary human malignant melanomas. Semin-Oncol 1975; 2: 83-103. Hill D, Boulter J. Sun protection behaviour -- determinants and trends, Cancer Forum 1996; 20: 204-211. Giles G, Thursfield V. Trends in skin cancer in Australia. Cancer Forum 1996; 20: 188-191. Hanrahan PF, Hersey P, D'Este CA. Factors involved in presentation of older people with thick melanoma. Med J Aust 1998; 169: 410-414. Giles G, Armstrong BK, Burton RC, et al. Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994. BMJ 1996; 312: 1121-1125. Hersey P, Sillar R, Howe CG, et.al., Factors related to the presentation of patients with thick primary melanomas. Med J Aust 1991; 154: 583-587. Hanrahan PF, Hersey P, Menzies SW, et al. Examination of the ability of people to identify early changes of melanoma in computer-altered pigmented skin lesions. Arch Dermatol 1997; 133: 301-311. Marks R, Jolley D, McCormack C, Dorevitch AP. Who removes pigmented skin lesions? A study of the ratio of melanoma to other benign pigmented tumors removed by different categories of physicians in Australia in 1989 and 1994. J Am Acad Dermatol 1997; 36: 721-726. Del Mar C, Green A, Cooney T, et al., Melanocytic lesions excised from the skin: what percentage are malignant? Aust J Public Health 1994; 18: 221-223. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

John W Kelly

Factors involved in presentation of older people with thick melanoma Pauline F Hanrahan, Peter Hersey and Catherine A D'Este MJA 1998; 169: 410-414 For editorial comment, see Kelly Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Oncology - ©MJA1998 Abstract Objective: To examine whether presentation of older people with thick melanoma is a result of the site and histological type or of their reduced ability to identify melanoma. Design and setting: Retrospective analysis of the Newcastle Melanoma Unit patient database. Patients: 2154 patients with melanoma for whom complete data (histological type, thickness and site of melanoma) were available and who presented from February 1981 to April 1997. Main outcome measures: Histological type and site of melanoma in older (≥50 years) versus younger men and women; frequency with which these groups identified melanoma and the first changes of melanoma that were noticed. Results: Patients aged ≥50 years, particularly men, were more likely to present with thicker lesions. Older men and, to a lesser extent, older women were more likely to present with nodular melanoma, which were more frequent on the scalp and face in older, compared with younger, men, and scalp and back in older men compared with older women. Failure to identify melanoma was associated with older age, sites on the scalp and back and histological type of the lesion, but was independent of sex once histological type, age, site and thickness were taken into account. Multivariate analysis indicated that the association of older age of patients with failure to identify melanoma applied irrespective of the site, type and thickness of their melanoma. Conclusion:. The higher frequency of thick melanoma in older people is accounted for by an increased proportion of nodular melanoma and decreased ability to recognise the changes of melanoma. These findings have important implications for examination of older patients by doctors and for design of strategies for early detection of melanoma in this age group. Introduction Survival from melanoma is related to thickness of the tumour. Ninety-six per cent of patients whose lesions are detected early (< 0.75 mm thick) will survive to 10 years,1,2 but this decreases to 50% for patients with lesions 4 mm or greater.3,4 Previous studies have shown that most patients who present with thick lesions are men aged over 50 years.5-7 In New South Wales over 50% of deaths from melanoma involve men over 50, even though this group comprises only 12%-14% of the population.8 Clearly, strategies that facilitate early detection of melanoma in older men may markedly reduce the death rate from this cancer. We have previously investigated the ability of older men to distinguish between benign and malignant pigmented skin lesions in photographs and whether an educational brochure assists this ability;9 the brochure increased knowledge of melanoma, but did not help participants distinguish between benign and malignant pigmented skin lesions. We then investigated whether this age group had inherent difficulties in recognising the changes of melanoma and found that all age groups had difficulty in recognising the appearance of new pigmented lesions and changes in lesions over time.10,11 Older people were no less able than younger people to identify change, but falsely identified changes in unchanged lesions more frequently. In this study we sought to examine factors associated with failure of patients to identify their melanoma and the importance of this in presentation of older patients with thick melanoma. Methods Information for the study was obtained from the database in the Newcastle Melanoma Unit (NMU), which was established in 1981 and is a referral centre for patients from the Hunter region of New South Wales. Over 90% of patients with melanoma in the Hunter region attend the unit. The database contains information obtained by experienced oncology nurses who interview patients, asking questions about changes they had noticed leading to diagnosis of melanoma, for how long they had noticed the changes and whether these were in a pre-existing or new lesion. The age and sex of patients, site of their primary lesion, its histological type and thickness were also recorded. Histological investigation of the lesions was reviewed by at least two pathologists and reported as described previously.12 Patient clinical data were entered into a program developed jointly by the Sydney Melanoma Unit and the Macquarie University using Clinical Reporting Systems software (Brisbane Road, Castle Hill, NSW). We included data for all patients presenting to the NMU between February 1981 and April 1997. The data were categorised for statistical analysis as follows. Patients were divided into two groups by age (< 50 and ≥50). As in a previous study,5 thickness of primary lesions was categorised as < 3 mm, or ≥3 mm. Data on the site of the primary melanoma were divided into seven categories (scalp, face, neck, back, anterior trunk, arm and leg). Melanomas were categorised into seven histological types (superficial spreading melanoma [SSM], nodular melanoma [NM], lentigo maligna [LM], in-situ melanoma, desmoplastic melanoma, unknown, and unclassified) of which we included only the first three relatively common types. Categories for types of changes were: unidentified (including instances where patients were uncertain whether a change had occurred, or said that no change had occurred, but melanoma was detected by their general practitioners or other doctors); size and shape; colour; changes in sensation (eg, itching, tingling); and bleeding. Statistical analysis Data were analysed with SAS13 and STATA14 statistical software. Lesion characteristics (thickness, histological type and site of melanoma) were compared by age and by sex separately using chi-squared analyses. Lesion characteristics and age and sex were also compared for those who had, and had not, identified any changes. Logistic regression analyses were performed to examine factors associated with identification of any changes of melanoma, using any change versus no change, as the outcome variable. All five independent variables were tested for significance by forward stepwise regression analysis. After the final main effects model was obtained, all possible interactions were tested. The likelihood ratio statistic was used to assess statistical significance in the logistic regression analyses. We also tested (by chi-squared analysis) lesion characteristics, age and sex for association with type of changes noticed; 95% confidence intervals (CI) were calculated for each type of change. A significance level of 0.05 was used for all analyses. Subgroups were considered to differ significantly if 95% CIs did not overlap. Results The database included records for 3435 patients who attended the NMU during the study period. Exclusions included: 932 patients for whom there was incomplete data or for whom data could not be appropriately classified; 325 with uncommon, unknown, desmoplastic or unclassified histological types of melanoma; and 22 with melanoma at unusual sites (eg, mucosal regions, buttocks, groin). The final sample of 2154 patients comprised 1144 men (53%) and 1010 women (47%); 1142 patients (53%) were aged 50 years or over and 59% of the men in the study were in this age group, compared with 46% of the women. There were no significant differences in sex or age of patients excluded compared with those included (sex: chi-squared = 0.006, df = 1, P = 0.94; age: chi-squared = 1.7, df = 1, P = 0.18). The site and thickness of melanomas were similar in those excluded and included. Excluded patients had a different distribution of histological types (as this was part of the basis for their exclusion) and a higher proportion of unnoticed changes than those included. More detailed information about excluded patients is available from the authors. Lesion characteristics Thickness: Box 1 shows that patients aged 50 years or over (14.5%; 95% CI, 12%-16%) were significantly more likely to present with thick lesions than younger patients (4.7%; 95% CI, 3%-6%), and men (12%; 95% CI, 10%-14%) were more likely to have thick lesions than women (7%; 95% CI, 6%-9%). Site: Melanoma was found most often on the backs of male patients (47%; 95% CI, 45%-50% v. 24%; 95% CI, 22%-27% for women), whereas the leg was the predominant site in women (38%; 95% CI, 35%-41% v. 16%; 95% CI, 13%-18% for men). The incidence of melanoma on the scalp, face and neck was similar for men and women. Melanoma on the arms was more common in women (19%; 95% CI, 16%-21% v. 12%; 95% CI, 10%-13% for men), while melanoma on the face was more common in older patients and melanoma on the anterior trunk and leg was more common in younger men than older men. Melanomas were more common on the scalp and face in older, compared with younger, men and more common on the scalp and back of older men compared with older women (Box 1). Histological type: SSM was more common in younger patients of both sexes and NM was more common in older male patients. Most thin lesions (80%) were SSM and most thick lesions (72%) were NM. Thicknesses of the three histological types were: SSM, 0.02-10.5 mm (median, 0.63 mm; interquartile range [IQR], 0.4-1.0 mm); NM, 0.2-25 mm (median, 2.46 mm; IQR, 1.4-3.8 mm); and LM, 0.1-8.5 mm (median, 0.4 mm; IQR, 0.25-0.8 mm). Factors associated with failure to identify melanoma Many melanomas were not detected by patients, but were identified by their doctors. Sex and age: Men were more likely to fail to notice changes of melanoma than women (37%; 95% CI, 35%-49% v. 30%; 95% CI, 28%-32%) as were older, compared with younger, people (38%; 95% CI, 35%-41% v. 28%; 95% CI, 25%-31%). As shown in Box 2, a greater proportion of older men failed to identify changes in their lesions than younger men; the same trend was evident in women. Site: Patients most frequently failed to identify changes in lesions on the scalp (42%; 95% CI, 30%-52%) and back (41%; 95% CI, 37%-45%), but even among patients with a lesion on the face, 31% (95% CI, 26%-33%) did not identify it as melanoma. The anterior trunk was the least common site for unidentified change (24%; 95% CI, 20%-28%). Older patients failed to identify changes more often than younger patients for all sites except the face and scalp, where the reverse was the case (Box 2). However, numbers are very small for these groups and results should be interpreted with caution. Histological type: A greater proportion of patients with LM (47%; 95% CI, 40%-55%) failed to identify their melanoma than patients with SSM (33%; 95% CI, 31%-35%) or NM (29%; 95% CI, 25%-33%), although by the time they were detected the NM were much thicker. Older people were less likely than younger people to identify melanoma of all three histological types. Regression analyses: Age, thickness, histological type and site of lesion were significantly associated with identifying changes (Box 3). After these variables were included in the model, sex was no longer statistically significant. After adjustment for other variables in the model, the odds of older people identifying changes was two-thirds the odds of younger people identifying changes, and the odds of those with thicker lesions identifying changes was one-and-a-half times the odds of those with thinner lesions identifying changes. Those with LM had about half the odds of identifying changes as those with NM. As shown in Box 3, those with lesions on the face, arm, anterior trunk and leg had significantly higher odds of identifying changes than those with lesions on the back (reference group). Associations with thick melanoma (≥3 mm) As shown in Box 3, age and nodular melanoma were strongly associated with presentation with thick lesions. Changes of melanoma were more frequently identified in thick lesions, but as shown in Box 2, older people were less able to identify melanoma, irrespective of its thickness. It was also of interest that once the histological type of the lesion was taken into account, the site of the melanoma and sex of the patient were no longer related to thickness (ie, thick melanoma on the back and scalp in men appeared to result from the higher frequency of NM at these sites in men; see Box 3). Types of changes reported by patients Significantly fewer older than younger men reported changes in size and shape (21% v. 30%). The same was true for colour (20% v. 27%), and twice as many older men stated that the first change they were aware of in their skin lesion was bleeding (7% v. 3%). However, these differences were not statistically significant. Similarly, our findings that more younger than older women reported colour changes as the first change noticed (32% v. 25%) and (in contrast to men) older women reported changes in size and shape as the first change as frequently as younger women (30% v. 28%), were also not statistically significant. As shown in Box 4, patients with NM reported changes in colour significantly less frequently than those with SSM, change in sensation significantly more frequently than those with LM, and bleeding significantly more frequently than those with LM and SSM. Changes in size and shape were the most frequent changes reported in thick melanoma (34%), whereas changes in colour were more frequently reported in thin lesions (27%). Bleeding was reported as the first change significantly more frequently in thick than thin lesions (17% v. 4%). Reported changes in sensation were similar for thick or thin lesions. Discussion We excluded approximately one-third of the patients on the NMU database, mainly because of missing information about changes noticed or thickness measurements, or because they had melanoma of unusual histological type or location. However, the excluded patients appeared to have similar age and sex distribution, site and thickness measurements to patients in the study. Nonetheless, our results may not be generalisable to patients with the less common histological types of melanoma. Forty per cent of men and 34% of women aged over 50 failed to identify their melanoma. In contrast, younger patients of both sexes reported changes of melanoma in over 70% of cases. These findings were consistent with those of Koh et al15 who found that 38% of melanomas were not identified by men over the age of 60, compared with 23% in men less than 40 years of age. We also found that failure to detect melanoma was not only related to the age of the patient, but was associated with the site and type of the melanoma. Firstly, older men had lesions at sites which are more difficult to see, such as the back and scalp, with nearly 50% of melanoma in older men (compared with only 20% in older women) occurring on the back. Other series have reported similar differences in site distribution of melanoma between the sexes.16,17 Secondly, compared with younger people, older people, particularly men, had a higher proportion of NM, similar to that reported elsewhere.5,18 Patients also identified NMs when they were much thicker than SSMs (median, 2.46 mm v. 0.63 mm). The higher frequency of bleeding as the first change noted in patients with NM was consistent with this finding.19 The higher proportion of NM in older people and more frequent occurrence in "hard-to-see" sites could solely explain the presentation of older people with thicker melanomas. However, regression analysis indicated that for any given thickness and type of melanoma at a given site, older people were less able to recognise melanoma than younger people. In our examination of the first change that drew the attention of patients to their melanoma, we found that self-reporting of a change in colour was infrequent in patients with thick melanoma, and in patients with NM relative to those with SSM. These results were surprising, as previous studies have shown that changes in colour were one of the most frequent early changes of melanoma.20,21 Most of the thick melanoma were NM, which tend to be relatively homogeneous in colour compared with SSM. Thus, the different patterns of colour between NM and SSM may need to be emphasised in educational material directed at older patients. Bleeding was clearly associated with thick and nodular melanoma, but this is a late rather than an early sign.19 To the best of our knowledge this is the first study that has sought to identify reasons why older people present with thicker melanoma. The finding that older patients had lower ability to detect melanoma than younger people is consistent with our previous findings that older people had difficulty in discriminating early changes of melanoma in photographs of pigmented lesions.10,11 Previous studies have noted that younger people were more likely to rate change in skin lesions as extremely important in diagnosis of melanoma than older respondents.22 Older people may also not inspect their skin as frequently as younger people and this may contribute to their lower rate of detection of melanoma. Our findings raise questions about the likely effectiveness for older people of public health strategies that rely on self-detection of melanoma. It seems that that greater reliance will need to be placed on detection of melanoma in this age group by health professionals, who may need to be made aware of the high frequency of thick melanoma and characteristics of melanoma in this age group. Our previous studies have shown that recognition of change in existing lesions over time or the appearance of new pigmented skin lesions can be very difficult, but is assisted by whole-body photographs.10,11 The feasibility of using whole-body photographs to help general practitioners detect melanoma is currently under evaluation in a project funded by the National Health and Medical Research Council. Acknowledgements We thank the nursing sisters Sue Collins, Debbie Bradley, Donna Owens and Kathy Hall for collection of the data and Vicky Hunter for data entry. Dr Hanrahan was supported in part by the Hunter Melanoma Foundation. References Buttner P, Garbe C, Bertz J, et al. Primary cutaneous melanoma: optimized cutoff points of tumor thickness and importance of Clarks level for prognostic classification. Cancer 1995; 75: 2499-2506. Thorn M, Ponten F, Bergstrom R, et al. Clinical and histopathologic predictors of survival of patients with malignant melanoma: a population based study in Sweden. J Natl Cancer Inst 1994; 86: 761-769. Balch CM, Soong SJ, Shaw HM, et al. An analysis of prognostic factors in 8500 patients with cutaneous melanoma. In: Balch CM, Houghton AN, Milton GW, et al, editors. Cutaneous melanoma. Philadelphia: JB Lippincott Co.; 1992: 165-185. Breslow A. Tumor thickness, level of invasion and node dissection in stage 1 cutaneous melanoma. Ann Surg 1975; 182: 572-578. Hersey P, Sillar R, Howe CG, et al. Factors related to the presentation of patients with thick primary melanomas. Med J Aust 1991; 154: 583-587. McHenry PM, Hole DJ, Mackie RM. Melanoma in people aged over 65 in Scotland, 1979-89. BMJ 1992; 304: 746-749. Cohen HJ, Cox E, Manton K, Woodbury M. Malignant melanoma in the elderly. J Clin Oncol 1987; 5: 100-106. Coates M, Day P, McCredie M, Taylor R. NSW cancer incidence and mortality 1992. In: NSW Central Cancer Registry. Sydney: NSW Cancer Council; June 1995: 87, 97. Hanrahan P, Hersey P, Watson AB, Callaghan TM. The effect of an educational brochure on knowledge and early detection of melanoma. Aust J Public Health 1995; 19: 270-274. Hanrahan P, Hersey P, Menzies SW, et al. Examination of the ability of older people to identify early changes of melanoma in computer-altered pigmented skin lesions. Arch Dermatol 1997; 133: 301-311. Hanrahan P. Early detection of melanoma in older people [PhD thesis]. Sydney: University of NSW, 1998. McGovern VJ, Cochran AJ, Van Der Esch EP, et al. The classification of malignant melanoma, its histological reporting and registration: a revision of the 1972 Sydney classification. Pathology 1986; 18: 12-21. SAS for PC [computer program]. Version 6.11. Cary, NC: SAS Institute Inc., 1995. STATA [computer program]. Version 5.0. Houston, Tx: Stata Corp, 1997. Koh HK, Miller DR, Geler AC, et al. Who discovers melanoma? J Am Acad Dermatol 1992; 26: 914-919. Nguyen HL, Armstrong B, Coates M. Cutaneous melanoma in NSW 1983-1995. In: NSW Central Cancer Registry. Sydney: NSW Cancer Council; June 1997: 40. Green A, MacLennan R, Youl P, Martin N. Site distribution of cutaneous melanoma in Queensland. Int J Cancer 1993; 53: 232-236. Nguyen HL, Armstrong B, Coates M. Cutaneous melanoma in NSW 1983-1995. In: NSW Central Cancer Registry. Sydney: NSW Cancer Council; June 1997: 38. Fitzpatrick TB, Milton GW, Balch CM, et al. Clinical characteristics of primary melanoma. In: Balch CM, Houghton AN, Milton GW, et al, eds. Cutaneous melanoma. 2nd ed. Philadelphia: JB Lippincott Co.; 1992: 225-226. Mackie RM. Clinical recognition of early invasive melanoma. BMJ 1990; 301: 1005-1006. McGovern TW, Litaker MS. Clinical predictors of malignant pigmented lesions. J Dermatol Surg Oncol 1992; 18: 22-26. Baade PD, Balanda KP, Stanton WR, et al. Community perceptions about the important signs of early melanoma. J Am Acad Dermatol 1997; 36: 33-39. (Received 1 Sep 1997, accepted 14 May 1998) Authors' details John Hunter Hospital, Newcastle, NSW. Pauline F Hanrahan, BA, PhD, Research Officer, Newcastle Melanoma Unit and Division of Surgery; Peter Hersey, FRACP, D. Phil, Conjoint Professor of Oncology, Oncology and Immunology Unit, Division of Surgery. Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW. Catherine A D'Este, BMath, PhD, Lecturer in Biostatistics, Faculty of Medicine and Health Sciences. Reprints will not be available from the authors. Correspondence: Dr P Hersey, Room 443, David Maddison Clinical Sciences Building, Cnr King and Watt Streets, Newcastle, NSW 2300. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Pauline F Hanrahan · Peter Hersey · Catherine A D'Este

Outcome measures of an Australian breast-screening program One surrogate measure of the quality and effectiveness of screening MJA 1998; 169: 179-180 Mammographic screening for the early detection of breast cancer is a population-based measure for which randomised controlled trials have shown a 30% reduction in mortality in women aged between 50 and 69 years and who are screened.1 It is often forgotten that Australia is one of only a few countries where the State (in the form of both Federal and State governments) funds a national program of mammographic screening. From the outset of this program, there was an insistence that a quality service was essential if the predicted mortality reduction benefits were to be realised. Thus, national quality benchmarks based on international data were set. These were incorporated into accreditation standards to apply to all services in all States and Territories. This 30% mortality reduction depended on achieving a screening rate of approximately 70% of the target population, but it was recognised that even with 100% participation an inadequate, poor-quality service would not deliver the goods. The national screening program was phased in from 1992 and now covers the whole country. The accreditation standards are achievable, but screening participation has yet to reach target, and it will be several more years before mortality statistics for breast cancer can be affected by screening. Surrogate measures for the effectiveness of the service are therefore needed. One predictor of future breast cancer mortality is the small cancer detection rate, and it is gratifying that most States and Territories have already achieved the national accreditation standard.2 Another predictor of the effectiveness of the screening program is the interval cancer rate measured at State and national levels. The interval cancer rate is usually defined as the rate of diagnosis of new cases of invasive breast cancer and ductal carcinoma-in-situ in the two-year interval after a screening examination. In this issue of the Journal Rickard et al report rates and proportional incidences of interval cancers in the 12 months after screening from a New South Wales pilot mammographic screening program.3 The proportional incidence is the proportion that interval invasive breast cancers comprise of the total number of invasive breast cancers expected in the absence of screening. While the proportional incidence reported by Rickard et al is lower than that reported in studies from the United Kingdom4 and the Netherlands,5 it is higher than that found in the Swedish Two-County Study.6 As the confidence intervals found in all these studies overlap, we cannot conclude that these differences are statistically significant. However, the lack of a statistically significant difference in the proportional incidence between the study by Rickard and colleagues3 and the Swedish one6 cannot be taken to mean that they will achieve a similar mortality reduction. Larger State-based and national studies are needed to make international comparisons. The 12-month interval-cancer incidence of 4.17 per 10 000 screens in the women aged 40-49 years and 4.64 per 10 000 screens in women aged 50-69 reported by Rickard et al3 are lower than that reported by the South Australian screening program.7 However, because the confidence intervals for the New South Wales rate3 include the SA estimate, these differences are not statistically significant. To calculate rates and proportional incidences of interval cancers, we need well-functioning, complete and up-to-date BreastScreen services and cancer registries in each of the States and Territories. This requires both political will and financial resources, at national and State levels. It is also essential that each program counts interval cancers in the same way. In the UK,8 different definitions of interval cancers gave estimates of the interval cancer rate which varied by nearly 30%. While the low 12-month incidence rate found by Rickard et al is promising, it is also important to measure this in the second year after screening, when interval cancers are likely to form a greater proportion of the expected incidence of breast cancer. Also, although this study is too small to present separate interval cancer rates for the first and second screening round, future studies must do this, as these rates may differ. Nevertheless, it is essential to recognise the need to measure interval cancer rates in breast screening in a consistent fashion, in each State and Territory as well as nationally. Although interval cancers are inevitable, they are a measure of the sensitivity of a program whose object is to ensure that a high proportion of women with cancer are diagnosed by the screening process. However, achieving the lowest possible interval cancer rate must not be done at the expense (financial and emotional) of recalling a high proportion of women for further assessment that would lead to high rates of false positives (as happened in one American service where one-third of women without cancer received an abnormal screening result over 10 years).9 BreastScreen Australia is just over five years old and in its infancy. It has attained a high level of awareness among women,10 with very high levels of acceptability as shown by high rescreening levels.11 Government funding permits a quality of screening not available in the world's first national program, in the United Kingdom -- double-view mammography, double specialist reading and a two-yearly screening interval. To ensure quality and to assess whether their stewardship of this national investment in women's health is likely to have produced the expected reduction in breast cancer mortality, programs should be encouraged not only to attain the accreditation standards, but also to use nationally agreed surrogate measures for overall mortality changes, of which interval cancer rates are but one. Further, governments must support their investment by encouraging and funding the collection and interchange of these nationally agreed data. Alan Rodger Professor and Director The William Buckland Radiotherapy Centre, The Alfred Health Care Group, Melbourne, VIC Anne M Kavanagh Public Health Research Fellow Cancer Epidemiology Centre, Anti Cancer Council of Victoria, Melbourne, VIC Hurley SF, Kaldor JM. The benefits and risks of mammographic screening for breast cancer. Epidemiol Rev 1992; 14: 101-103. National Program for the Early Detection of Breast Cancer -- national accreditation requirements: March 1994. Canberra: Commonwealth Department of Human Services and Health, December 1994. Rickard MT, Taylor R, Fazli MA, El Hassan N. Interval breast cancers in an Australian mammographic screening programme. Med J Aust 1998; 169: 184-187. Woodman CBJ, Threlfall AG, Boggis CRM, Prior P. Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region. BMJ 1995; 310: 224-226. Peeters PHM, Verbeek ALM, Hendricks JHCL, et al. The occurrence of interval cancers in the Nijmegen screening programme. Br J Cancer 1989; 59: 929-932. Tabar L, Faberberg G, Day NE, Holmberg L. What is the optimum interval between mammographic screening examinations? An analysis on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 1987; 55: 547-551. Robinson JL, Crane CEB, King JM, et al. The South Australian breast x-ray service: results from a statewide mammographic screening programme. Br J Cancer 1996; 73: 837-842. Faux AM, Richardson DC, Lawrence GM, et al. Interval breast cancers in the NHS breast screening programme: does the current definition exclude too many? J Med Screening 1997; 4: 169-173. Elmore JG, Barton MB, Moceri VM, et al. Ten-year risk of false positive screening mammograms and clinical breast examination. N Engl J Med 1998; 338: 1089-1096. Barratt AL, Cockburn J, Redman S, Perkins PC. Mammographic screening: results from the 1996 National Breast Health Survey. Med J Aust 1997; 167: 521-524. BreastScreen Victoria. Annual Statistical Report 1996. Melbourne: Victorian Breast Screening Co-ordination Unit Inc., 1996: 12. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Alan Rodger · Anne M Kavanagh

Interval breast cancers in an Australian mammographic screening program Mary T Rickard, Richard J Taylor, Mohamed A Fazli and Nadima El Hassan MJA 1998; 169: 184-187 For editorial comment, see Rodger & Kavanagh Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the incidence of interval cancers which occurred in the first 12 months after mammographic screening at a mammographic screening service. Design: Retrospective analysis of data obtained by crossmatching the screening Service and the New South Wales Central Cancer Registry databases. Setting: The Central & Eastern Sydney Service of BreastScreen NSW. Participants: Women aged 40-69 years at first screen, who attended for their first or second screen between 1 March 1988 and 31 December 1992. Main outcome measures: Interval-cancer rates per 10 000 screens and as a proportion of the underlying incidence of breast cancer (as estimated by the underlying rate in the total NSW population). Results: The 12-month interval-cancer incidence per 10 000 screens was 4.17 for the 40-49 years age group (95% confidence interval [CI], 1.35-9.73) and 4.64 for the 50-69 years age group (95% CI, 2.47-7.94). Proportional incidence rates were 30.1% for the 40-49 years age group (95% CI, 9.8-70.3) and 22% for the 50-69 years age group (95% CI, 11.7-37.7). There was no significant difference between the proportional incidence rate for the 50-69 years age group for the Central & Eastern Sydney Service and those of major successful overseas screening trials. Conclusion: Screening quality was acceptable and should result in a significant mortality reduction in the screened population. Given the small number of cancers involved, comparison of interval-cancer statistics of mammographic screening programs with trials requires age-specific or age-adjusted data, and consideration of confidence intervals of both program and trial data. Introduction The principal aim of a mammographic screening service is to reduce mortality from breast cancer. As this outcome cannot be measured effectively for many years after the establishment of screening, and as it applies to spatially defined populations, a range of interim measures are used to evaluate screening services and to determine the likelihood of mortality reduction. Interim measures include screen-detected cancer rates and the rates of prognostic indicators for these cancers, such as size, nodal status and grade.1 Another interim measure of screening performance is the interval-cancer rate.2,3 As survival among women with interval cancers is similar to that among unscreened women, then as the incidence of interval cancers approaches that of the underlying incidence of breast cancer the benefit of screening disappears.3 Interval-cancer rates can be compared with background or underlying rates to better assess the effectiveness of screening. Further, comparing the rate of interval cancers with the underlying rate allows comparison between different screening programs in populations with different incidences of breast cancer. Our aim was to evaluate first-year interval breast cancers after screening at the Central & Eastern Sydney Service of BreastScreen NSW (a mammographic screening and assessment service). We report the incidence and proportional incidence of interval breast cancers during the 12 months after both the first and second rounds of screening, over five years. Methods The Central & Eastern Sydney Service of BreastScreen NSW is located in inner Sydney, and started screening in March 1988 as one of the first pilot mammography screening programs in Australia. Any woman aged 40 years or more was eligible to attend, although during the study period only 50-69-year-old residents in the Central Sydney Area Health Service were actively recruited for two-yearly screening. Since the progressive introduction of systematic, government-funded, population-based screening from 1991, the Service has become a regional component of BreastScreen NSW and BreastScreen Australia.4The study population comprised women who attended the Service for mammographic screening between 1 March 1988 and 31 December 1992. These women were all screened by two-view mammography. The technical quality of the Service's screening mammograms met all requirements for accreditation by BreastScreen Australia.5 All films were read independently by two radiologists and were reported as "normal" for routine rescreen or as "suspicious" and requiring assessment. The design of the screening and assessment Service has been previously described.6 Screen-detected cancers The definition of primary breast cancer used for this study includes invasive cancer and ductal carcinoma-in-situ (DCIS), but excludes lobular carcinoma-in-situ.5 All cases of primary breast cancer diagnosed by the screening and assessment Service in women attending for the first time were classified as prevalent (first-round) screen-detected cancers. Cancers in women attending for their first routine rescreen after two years were classified as second-round screen-detected cancers. Data were analysed according to age at first screen, by 10-year age groups (40-49, 50-59 and 60-69 years). Interval cancers We reviewed the data for interval cancers, defined as primary cancer of the breast diagnosed up to 12 months after a first-round or second-round screening mammogram in women aged 40-69 years at the time of screening. The date of diagnosis of these interval cancers was taken as the date of histological confirmation of cancer. Cases in which clinical and imaging findings were consistent with breast cancer but no surgery had been performed were included in the study and the date of diagnosis was taken as the date of cytological confirmation of cancer. Data were analysed by women's age at their first screen. Some interval cancers were reported to the screening Service and others were identified by linking the Service's screening database with the NSW Central Cancer Registry (NSW CCR), which has operated since 1972 as a population-based registry. Notification of malignant neoplasms has been a statutory requirement for all NSW public and private hospitals, radiotherapy departments and nursing homes since 1972, and for pathology and outpatient departments since 1985. The date of diagnosis used by the NSW CCR was defined as "date of first definitive treatment for cancer" during the period covered by this study, although incidence was designated mostly on the basis of the first notification (usually the biopsy report). We matched records of the screening database with the NSW CCR in late 1994 with the aid of probabilistic linkage7,8 using Automatch.9 Equivocal matches were investigated by individual examination of all details available, and by active follow-up by the screening Service. Positive linkages between the screening database and the cancer registry were investigated by the screening Service to ensure that all data on those interval cancers diagnosed in the first year after a negative screen were available for inclusion in the study. Statistical analysis The age-specific incidence of interval cancers was determined by dividing the number of interval cancers found in women screened between 1988 and 1992 by the age-specific (age at first screen) number of women screened over the same period. Age groups were 40-49, 50-59 and 60-69 years, although the latter two age groups are aggregated for reporting purposes. The underlying incidence of breast cancer from 1988 to 1992 was obtained by dividing NSW reported cases (as reported by the NSW CCR.10,11) by the State female population for the same three 10-year age groups. To express the interval-cancer incidence as a proportion of the underlying breast cancer incidence rate, an indirectly age-standardised incidence ratio12 was calculated using the State age-specific incidences as the standard. Because of small numbers of cases, 95% confidence intervals were derived by the Poisson method.12,13We compared our findings with those of studies from Sweden,3 the Netherlands14 and the United Kingdom15 using the 12-month interval-cancer data from the first two screening rounds for all studies except the UK study, for which only the first-round data were available. Confidence limits for interval-cancer rates from comparison populations were calculated from the published data using the same Poisson method as above. Results During the study period, the Central & Eastern Sydney Service carried out 39 988 first-round and second-round screens on women aged 40-69 years, and 226 screen-detected cancers were diagnosed. In the prevalent (first-round) screens, the screen-detected cancer rates per 1000 screens were 3.0 for women aged 40-49 years, 6.2 for 50-59-year-olds and 9.6 for 60-69-year-olds. Second-round rates were 3.5, 4.2 and 4.6, respectively. Eighteen interval cancers occurred in the first 12 months after screening. All of these interval cancers were invasive. The 12-month interval-cancer incidences are shown in Box 1. The underlying annual breast cancer incidences were 13.8 per 10 000 for the 40-49 years age group and 21.2 per 10 000 for the 50-69 years age group (19.4 for 50-59 years and 23.2 for 60-69 years). The interval-cancer incidences as a proportion of these underlying incidences are shown in Box 2, in which they are compared with those of the Swedish Two-County Study.3 The proportional interval-cancer incidence for women aged 50-69 years in the Central & Eastern Sydney Service (22.0%; 95% CI, 11.7%-37.7%) is compared with that for similar age groups from international studies3,14,15 in Box 3. The proportional interval-cancer incidence point estimate for the Central & Eastern Sydney Service was higher and had wider 95% confidence intervals than that of the Swedish Two-County Study (13.2%; 95% CI, 8.4-19.9), but was lower than that of the UK (31.4%; 95% CI, 24.9-39.1) and Dutch (39.5%; 95% CI, 20.4-69.0) studies. Discussion The screen-detected cancer rates achieved by the Central & Eastern Sydney Service exceed the National Accreditation Requirements and compare favourably with those reported from the Swedish Two-County Study and the other Australian mammographic screening services.5,16,17Our findings indicate that the first 12-month interval-cancer rate (as a proportion of underlying incidence) for women attending the Central & Eastern Sydney Service is higher than that of the Swedish Two-County Study,3 but lower than the rates reported from Nijmegen (the Netherlands)14 and North West Region UK.15 However, there is considerable overlap of 95% confidence intervals, and the conclusion must be that the Central & Eastern Sydney proportional first-year interval-cancer rate is not significantly different from that in these other studies. As a proportion of interval cancers occur because an abnormality has not been detected at the time of screening, the first-year interval-cancer rates reflect the proportion of false negative screens in the screening episode. The Central & Eastern Sydney results therefore indicate acceptable screening sensitivity and, as they are not significantly different from the results of the Two-County Study, they would be expected to indicate a similar future mortality reduction. The interval-cancer data presented in this study are not affected by significant ascertainment bias. Restricting our analysis to interval cancers occurring within the first year after a screen eliminates the difficulties of accurately differentiating interval cancers and screen-detected cancers diagnosed around the 21-27-month rescreen interval. We directed considerable attention to the linkage with the NSW CCR to ensure that no interval cancers were missed. The underlying rate of breast cancer is reliable. This was determined in a population that included the women who were screened. However, during the study period, the Central & Eastern Sydney BreastScreen Service was one of only two pilot mammographic screening and assessment endeavours in New South Wales, and screened a small fraction of the State's female population. Its clientele was not limited to the immediate geographic area. For the busiest years in this period (1991 and 1992) less than 5% of breast cancers in NSW were detected through these two mammographic screening services.18 Completeness of enumeration is difficult to determine precisely for cancer registries, but the standard indicators suggest reasonably good completeness for the NSW CCR,10,19 and its data are accepted for inclusion in Cancer incidence in five continents.20 Comparisons of the Central & Eastern Sydney Service and another pilot mammographic screening service with the NSW CCR for the period 1988-1992 showed 100% enumeration of invasive breast cancer by the NSW CCR (R T, NSW Cancer Council, unpublished data). The design of the Australian mammographic screening program and the comparison studies in this paper differ. The Swedish Two-County Study employed single-view mammography and double reading. The Dutch and UK studies used single-view mammography and single reading. Double-view mammography and double reading, as used in Australia, would be expected to produce better results and fewer interval cancers in the first year than the comparison studies. The confidence intervals of the proportional interval-cancer rates from the Swedish Two-County Study and those reported for North West Region UK do not overlap, and direct statistical testing has shown a significant difference between these rates.15 The authors of the UK article15 and those of the accompanying editorial21 expressed concern that the screening sensitivity in the British National Health Service program may not be sufficient to achieve mortality reduction targets. They noted the increased sensitivity resulting from two-view mammography, good film quality and two independent film readings. These features are part of BreastScreen Australia and of the Central & Eastern Sydney Service. Even when data are collected over reasonable lengths of time, the numbers of interval cancers in many screening services are often small because of the size of the base populations. In the 50-69 years age group, there were 23 interval cancers in the Swedish Two-County Study, compared with 12 in the Nijmegen study and 13 in our study. However, performance can still be evaluated through calculation of interval-cancer rates, provided that interpretation is qualified by consideration of confidence intervals based on exact or Poisson methods. Australian mammography screening services are evaluated by comparison with National Accreditation Requirements standards.5 The point estimate of the Swedish Two-County Study has come to be regarded as a standard, as this study achieved significant mortality reduction. However the Two-County Study did not involve large numbers, and its interval-cancer rates must be interpreted in relation to their statistical confidence intervals. That is, standards cannot be derived from point estimates alone as they emanate from real studies in real populations. Further, comparison of the performance of screening services with such standards also requires that the confidence intervals of the screening service data be taken into account. Evaluations should not be based on point estimates of rates which derive from small numbers with considerable stochastic variation. The standard for Australian National Accreditation Requirements is less than six interval cancers per 10 000 screens occurring in the first 12 months. However, no age range or standardisation is specified, and confidence intervals are not considered. Another consideration in setting performance standards for mammographic screening services is the difference in results from experimental and operational studies. Randomised trials and other specially constructed studies usually attract significant financial resources and interested investigators. It may be more reasonable to derive standards from studies of operational mammographic screening services whose data, when sufficient studies have been reported, could be assessed to determine performance standards which could reasonably be expected. However, until operational mammography screening services have been shown to produce reduced breast cancer mortality in the screened populations, the results of successful trials must set the gold standard. Acknowledgements The Central & Eastern Sydney Service of BreastScreen NSW and BreastScreen Australia is jointly funded by the Commonwealth and the NSW State Governments. The NSW Central Cancer Registry, which is administered by the NSW Cancer Council and funded by the NSW Health Department, provided valuable assistance with data linkage. References Duffy SW, Tabar L, Fagerberg G, et al. Breast screening, prognostic factors and survival -- results from the Swedish two county study. Br J Cancer 1991; 64: 1133-1138. Day NE, Williams DRR, Khaw KT. Breast cancer screening programmes: the development of a monitoring and evaluation system. Br J Cancer 1989; 59: 954-958. Tabar L, Fagerberg G, Day NE, Holmberg L. What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 1987; 55: 547-551. Australian Health Ministers' Advisory Council. Breast Cancer Screening Evaluation Committee. Breast cancer screening in Australia: future directions. Australian Institute of Health, Prevention Program Evaluation Series No. 1. Canberra: AGPS, 1990. National Program for the Early Detection of Breast Cancer -- national accreditation requirements: March 1994. Canberra: Commonwealth Department of Human Services and Health, December 1994. Rickard MT, Lee W, Read JW, et al. Breast cancer diagnosis by screening mammography: early results of the Central Sydney Area Health Service Breast X-Ray Program. Med J Aust 1991; 154: 126-131. Fellegi IP, Sunter AB. A theory for record linkage. J Am Statistical Assoc 1969; 64: 1183-1210. Jaro M. Advances in record linkage methodology as applied to matching the 1985 census of Tampa, Florida. J Am Statistical Assoc 1989; 84: 414-420. Jaro M. Automatch. Generalised record linkage system. Silver Spring, Md: Matchware Technologies Inc, USA, 1994. Taylor R, Smith D, Hfyer A, et al. Breast cancer in New South Wales 1972-91. Sydney: NSW Central Cancer Registry and Cancer Epidemiology Research Centre, NSW Cancer Council, September 1994. Coates M, Day P, McCredie M, Taylor R. Cancer in NSW, incidence and mortality 1992. Sydney: NSW Central Cancer Registry and Cancer Epidemiology Research Centre, NSW Cancer Council, 1995. Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford: Scientific Publications, 1994. Lentner C, editor. Geigy scientific tables. Volume 2: Poisson distribution. Basle, Switzerland: Ciba-Geigy, 1982: 152. Peeters PHM, Verbeek ALM, Hendriks JHCL, et al. The occurrence of interval cancers in the Nijmegen screening programme. Br J Cancer 1989; 59: 929-932. Woodman CBJ, Threlfall AG, Boggis CRM, Prior P. Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region. BMJ 1995; 310: 224-226. Rickard MT, Donnellan M. Diagnosis of small sized invasive breast cancer by an Australian mammography screening service: surrogate end points for mortality reduction. Aust N Z J Surg 1998; 68: 426-429. Robinson JI, Crane CEB, King JM, et al. The South Australian Breast X-Ray Service: results from a statewide mammographic screening programme. Br J Cancer 1996; 73: 837-842. Smith D, Oudod V, Supramaniam R, et al. BreastScreen NSW. Statistical Report 1991-1995. Sydney: NSW Cancer Council, 1996. Coates M, McCredie M, Armstrong B. Cancer in NSW, incidence and mortality 1993. Sydney: Cancer Control Information Centre, NSW Cancer Council, 1996. Parkin DM, Muir CS, Whelan SL, et al, eds. Cancer incidence in five continents. Volume VI. World Health Organization (WHO), International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC). Lyon: IARC, 1992. (IARC Scientific Publication No. 120.) Field S, Michell M J, Wallis MGW, Wilson ARM. What should be done about interval breast cancers? BMJ 1995; 310: 203-204. (Received 7 Aug 1997, accepted 3 Apr 1998) Authors' details BreastScreen NSW, Central & Eastern Sydney, Sydney, NSW. Mary T Rickard, FRACR, MPH, Director and Radiologist; Mohamed A Fazli, BScEng, ME, Database Manager; Nadima El Hassan, BEc(Hons), Computer Consultant. Department of Public Health and Community Medicine, Faculty of Medicine, University of Sydney, Sydney, NSW. Richard J Taylor, FAFPHM, FRCP, Associate Professor in Public Health. Reprints will not be available from the authors. Correspondence: Dr M T Rickard, BreastScreen NSW, Central & Eastern Sydney, PO Box 1535, Strawberry Hills, NSW 2012. E-mail: MaryATces.bci.org.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Mary T Rickard · Richard J Taylor · Mohamed A Fazli

Prostate-specific antigen testing for prostate cancer: the case for informed consent Informed consent should be obtained before testing asymptomatic men MJA 1998; 169: 9-10 The prostate-specific antigen (PSA) test is only the first step in screening asymptomatic men for prostate cancer. Its lack of specificity usually necessitates transrectal ultrasound-guided multiple biopsies for confirmation of the diagnosis. These procedures will discover a large number of cancers, many of which, viewed from one perspective, will be potentially curable by surgery1 or radiotherapy. However, epidemiological evidence suggests that most cancers localised to the prostate will not cause clinically significant disease for at least 10 years.2 PSA-based screening presents unique difficulties because at present there is no means to distinguish those cancers which will impair health to a degree that justifies the risk of iatrogenic morbidity of investigation (biopsy-related sepsis) and curative treatment (incontinence, impotence, and radiation damage to adjacent organs). This issue of the Journal includes four pertinent articles: the incidence of prostate cancer and the prevalence of PSA testing are described and compared in Western Australia3 (Threlfall et al) and New South Wales4 (Smith & Armstrong); reasons for PSA tests being ordered by general practitioners (GPs) in central Sydney are reported5 (Ward et al); and the prevalence of PSA testing among South Australian men is given, together with findings concerning men's understanding of the immediate consequences of having a PSA test6 (Pinnock et al). PSA tests were the sixth most frequent pathology item ordered by GPs in the June quarter of 1996,5 but their use has fallen since the peak in 1995.3,4 This may indicate that GPs are adopting a more discerning approach, in line with guidelines that recommend against the use of PSA tests to screen for prostate cancer.7 However, in the period 1992-1996, it is clear that GPs and asymptomatic men adopted the test enthusiastically. Medicare data show that one in every four Australian men (27%) aged at least 50 years had a PSA test in 1995 or 19964 and, in a random survey of households in South Australia carried out in 1996, 28% of men aged 50 years or older without prostate cancer reported having a PSA test in the preceding 12 months.6 A high proportion of PSA tests were ordered by GPs for screening ("routine for age") or in response to patient request.5,6 Men over 70 years old have been tested as frequently as younger men4,6 -- but the older the man when prostate cancer is detected, the less likely it is that a benefit from early intervention is possible.8 In South Australia, there was an association between PSA testing and visiting a doctor for urinary symptoms.6 PSA testing is not recommended for men presenting with uncomplicated lower urinary tract symptoms (because such symptoms are unlikely to be indicative of localised prostate cancer),6,9 but it is understandable that GPs may order the test because the question of prostate disease has been raised during the consultation. It is evident that PSA tests have been carried out without the consequences of an abnormal test result being adequately explained.6 GPs need a clear-cut structured framework within which the paucity of good scientific evidence and the potential harms and benefits can be discussed with patients. Most GPs will have had difficulty reconciling the negative evidence relating to the cost-benefit of PSA testing with their natural inclination to detect and treat cancer at an early stage. However, in asymptomatic people the balance of harm versus benefit must demonstrably be more clearly in favour of benefit than in usual clinical practice. In the United States, where enthusiasm for both case-finding by PSA testing and treatment by radical prostatectomy occurred some years earlier than in Australia, there appears to have been a small fall in mortality from prostate cancer in the period 1990-1995.10 Interpretation of this fall is far from clear, but it may be attributable to the dramatic increase in use of radical prostatectomy11 or other therapeutic advances in the 1980s. Conclusive evidence of reduced mortality from prostate cancer as a result of PSA screening must await the completion of randomised controlled trials. From an intention-to-treat analysis of men aged 50-79 years with clinically localised prostate cancer in the population-based US Surveillance, Epidemiology, and End Results (SEER) Program, no advantage in 10-year disease-specific survival was found for either radical prostatectomy or radiotherapy compared with conservative management for men with tumours with a Gleason score of 2-4 (well differentiated).12 For men with tumours with a Gleason score of 5-7 (moderately differentiated) there was an advantage for radical prostatectomy but not for radiotherapy -- this may reflect the fact that patients selected for surgery excluded those whose general health, and therefore prognosis, was already bad when prostate cancer was diagnosed. The 10-year disease-specific survival was better for men with tumours with a Gleason score of 8-10 (poorly differentiated) treated by either radical prostatectomy or radiotherapy compared with conservative management. Because of the way screening for breast and cervical cancers has been promoted, the general public will perceive that finding a cancer earlier is beneficial because treatment is more likely to be effective. However, using the PSA test for detecting prostate cancer in asymptomatic men is not analogous to mammography for early detection of breast cancer in asymptomatic women. Apart from the unproven benefit, there is a need for universally applied guidelines for the management of men with an abnormal test result, comparable with those built into the mammographic screening program. Such guidelines would include counselling and provision for a multidisciplinary approach when a decision is being made about the best course of management. At present, the cascade of events following an abnormal PSA test result proceeds without the man always making an informed choice before the test. Indeed, when men are given prior information about the PSA test and its characteristics, the consequences of having a raised PSA level, follow-up diagnostic procedures, treatment options and side effects, they are less likely to decide to have the test.13 GPs have a professional responsibility to give appropriate advice based on current evidence and, where there is uncertainty, this should be conveyed. Obtaining informed consent is accepted in the context of an invasive procedure. Given the medical uncertainties, the invasive nature of the confirmatory and therapeutic procedures that will be required if the test is positive, and the possibility of doing more harm than good, informed consent should be obtained from asymptomatic men before ordering a PSA test. Margaret McCredie Professorial Research Fellow, Department of Preventive and Social Medicine University of Otago, Dunedin, New Zealand, and Cancer Epidemiology Research Unit, NSW Cancer Council, Woolloomooloo, NSW Brian Cox Senior Research Fellow, Department of Preventive and Social Medicine University of Otago, Dunedin, New Zealand Kaye KW. Prostate cancer: enthusiasm for screening. Med J Aust 1995; 162: 540-541. Johansson J-E, Adami H-O, Andersson S-O, et al. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA 1992; 267: 2192-2196. Threlfall TJ, English DR, Rouse IL. Prostate cancer in Western Australia: trends in incidence and mortality from 1985 to 1996. Med J Aust 1998; 169: 21-24. Smith DP, Armstrong BK. Prostate-specific antigen testing in Australia and association with prostate cancer incidence in New South Wales. Med J Aust 1998; 169: 17-20. Ward JE, Gupta L, Taylor NJ. Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer? Med J Aust 1998; 169: 29-31. Pinnock CB, Weller DP, Marshall VR. Self-reported prevalence of prostate-specific antigen testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. Fleming C, Wasson JH, Albertsen PC, et al. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. Prostate Patient Outcomes Research Team. JAMA 1993; 269: 2650-2658. National Health and Medical Research Council. Clinical practice guidelines. The management of uncomplicated lower urinary tract symptoms in men. Canberra: AGPS, 1996. Mettlin CJ, Murphy GP. Why is the prostate cancer death rate declining in the United States? Cancer 1998; 82: 249-251. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Lu-Yao GL, Yao S-L. Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet 1997; 349: 906-910. Flood AB, Wennberg JE, Nease RF, et al. The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team. J Gen Intern Med 1996; 11: 342-349. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Margaret McCredie · Brian Cox

Management of localised prostate cancer: state of the art The decision to treat should be based on the age of the patient and the grade of the cancer MJA 1998; 169: 11-12 We know that the incidence of prostate cancer increases with age and that many men "die with, but not from, prostate cancer".1 This has made the medical community concerned that, because of the high prevalence of comorbid illnesses among elderly men, many cancers detected by screening based on prostate-specific antigen (PSA) testing will be clinically insignificant, and that most patients would be overtreated. Unfortunately, we are also faced with the reality that approximately 2500 men succumb to prostate cancer annually, and many, particularly younger men, in fact "die of the disease and not with it".2 Most patients with localised prostate cancer will be given three management options: watchful waiting, radiotherapy, or radical surgery. Watchful waiting is defined as no initial treatment, with regular patient surveillance (which involves frequent consultations, digital rectal examinations and PSA testing) and commencement of androgen ablative therapy when clinical progression occurs. The success of watchful waiting depends on the predicted biological aggression of the cancer (related to the histological grade), as well as on the age and the associated comorbid illnesses of any individual patient. A pooled analysis of 828 patients treated conservatively in six non-randomised studies concluded that histologic grade was an important determinant of outcome. The 10-year cause-specific survival of patients with well or moderately differentiated cancers was 87%, compared with only 36% for those with poorly differentiated disease (who were at high risk of cancer progression and death).3 The cancer had metastasised by 10 years in 19% of men with well differentiated disease and 42% of men with moderately differentiated disease, despite the satisfactory cause-specific survival. Although watchful waiting may be an appropriate treatment choice for men with life expectancy of less than 10 years with well or moderately differentiated cancers, the outcome at 15 years may be less favourable. In another series, among men who survived more than 10 years from their initial diagnosis, prostate cancer was the direct or contributing cause of death in 63%.4 A report from the Connecticut Tumour Registry has shown that in men diagnosed with moderately differentiated cancer there is a modest, but not insignificant, risk of death from prostate cancer (28%) at 15 years with conservative treatment, and a potential loss of 4-5 years of life.5 Both mortality and potential years of life lost were even higher in men diagnosed with poorly differentiated disease. Contemporary radiotherapy offers an alternative to radical surgery for men who prefer not to undergo surgery or who have comorbidities which increase the risks of surgery. It also offers a chance of local tumour control to men with locally advanced cancer deemed unsuitable for curative surgery. There has been debate over the contribution of radiotherapy because surgery achieves higher rates of clinical and biochemical freedom of disease in the long term (although there have been no valid prospective, randomised controlled trials which directly compare these two treatments). However, the apparent advantage of surgery could be a reflection of the use of radiotherapy in patients with more advanced disease than those for whom radical prostatectomy would be contemplated. Success with radiotherapy has been shown to be dependent on both the stage and grade of the cancer. Fifteen-year cause-specific survival rates varied from 84% for low-stage to 52% for high-stage clinically localised cancers, and from 85% for well differentiated to 32% for poorly differentiated cancers.6 Traditional external beam radiotherapy involves a treatment course lasting up to seven or eight weeks. Acute proctitis and cystitis occurs in most patients, and there is a 2%-3% risk of long term rectal morbidity (diarrhoea, rectal bleeding) and a 30%-60% risk of permanent impotence. There are increasingly convincing data to support the hypothesis that local control and disease-free survival rates in patients with apparently localised disease improve with increasing radiation dose.7 Current research strategies are therefore aimed at increasing radiation dose without increasing surrounding normal tissue damage. This may be achieved by three-dimensional conformal therapy or brachytherapy, either alone or in combination with external beam radiotherapy. Another approach is to use androgen ablation to shrink the tumour, and then to deliver radiotherapy to maximise tumour cell kill.8 All these techniques have shown encouraging preliminary results, but follow-up has been relatively short. Improvements in surgical techniques, together with an increased understanding of the anatomy of the prostate, have made radical prostatectomy a popular treatment option for localised prostate cancer since the mid 1980s. A Mayo Clinic review of 3170 men treated by radical prostatectomy for clinically localised disease included 93% of men with clinically palpable disease and 25% with poorly differentiated disease. Cause-specific survival among those with palpable disease at 10 and 15 years was 90% and 82%, respectively, and 82% and 71%, respectively, among those with poorly differentiated cancers.9 The morbidity of radical surgery in an Australian setting has been discussed recently in the Journal.10 Independently administered questionnaires indicated that incontinence requiring daily pads occurred in approximately 10% of men who underwent surgery. Most of those affected required a maximum of one pad per day and the degree of inconvenience was generally low. The nerve-sparing technique may give reasonable postoperative potency rates in selected younger patients,11 but impotence occurs in most older men, and this is the issue that most affects quality of life.10 Nonetheless, men in most series indicated that they would choose to have surgery again,10 suggesting that the patients' desire to be cured of the disease outweighed the disadvantageous side effects. In a comparison of watchful waiting, radiotherapy and surgery, Surveillance, Epidemiology and End Results (SEER) data from the United States have shown that men with well differentiated cancer treated by watchful waiting have 10-year cause-specific survival rates comparable to those treated actively, while in those with moderately or poorly differentiated cancers treatment provides a survival benefit (Table).12 The gap between these groups is likely to widen further at 15 years as more men treated by watchful waiting live long enough to succumb to the disease. In most watchful waiting series, the mean age of the patients is over 70 years, and therefore few patients (5.9%-8.9%) actually survived 15 years.5,13 A recent study comparing 10-year data with 15-year data for men treated conservatively has shown a 15% reduction in cause-specific survival over the additional five years in men with well or moderately differentiated cancer,14 indicating a cumulative increase in prostate cancer mortality even in this cohort with lower grades of cancer. The hypothesis that death rates are declining as a result of increased diagnosis of localised disease treated at an earlier stage is supported by recent National Cancer Institute data showing that prostate cancer mortality in younger white men had declined by 11.7% this decade.15 It is to be hoped that randomised controlled trials currently under way will provide evidence that this is the case. A preliminary report suggests that this may be so.16 However, until the substantive results of these trials are known, men must be thoroughly counselled about the benefits and risks of early detection and treatment of prostate cancer. Aggressive, early therapy should be recommended for patients who are more likely to benefit from treatment -- those with greater than 10-year life expectancy, especially if diagnosed with a higher histological grade of cancer -- while patients less likely to benefit should be spared the morbidity of treatment. Mark Frydenberg Clinical Associate Professor, Department of Surgery, Monash University Head of Urology, Monash Medical Centre, Melbourne, VIC Gillian Duchesne Associate Professor, Department of Urology and Radiation Oncology Peter MacCallum Cancer Institute, Melbourne, VIC Phillip D Stricker Attending Urologist, Department of Urology, St Vincent's Hospital, Sydney, NSW Canstat -- Cancer in Victoria. Melbourne: Anti-Cancer Council of Victoria, 1994. Albertsen PC, Murphy-Setzko MA, Hanley JA, et al. Long term survival following conservative management of localised prostate cancer: fifteen year follow up among men aged 55-75 [abstract]. J Urol 1998; 159: 251. (Abstract No. A963.) Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative treatment of clinically localised prostate cancer. N Engl J Med 1994; 30: 242-248. Aus G, Hugosson J, Norlen L. Long term survival and mortality in prostate cancer treated with non-curative intent. J Urol 1995; 154: 466-469. Albertsen PC, Fryback DG, Storer BE, et al. Long term survival among men with conservatively treated localised prostate cancer. JAMA 1995; 274: 626-631. Bagshaw MA, Cox RS, Hancock SL. Control of prostate cancer with radiotherapy: long term results. J Urol 1994; 152: 1781-1785. Hanks GE, Martz KL, Diamond JJ. The effect of dose on local control of prostate cancer. Int J Radiat Oncol Biol Phys 1988; 15: 1299-1305. Zagars GK, Johnson DE, Von Eschenbach AC, Hussey DH. Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long term results of a prospective randomized study. Int J Radiat Oncol Biol Phys 1988; 14: 1085-1091. Zincke H, Oesterling JE, Blute ML, et al. Long term results after radical prostatectomy for clinically localised prostate cancer. J Urol 1994; 151: 1583-1586. Heathcote PS, Mactaggart PN, Boston RJ, et al. Health related quality of life in Australian men remaining disease free after radical prostatectomy. Med J Aust 1998; 168: 483-486. Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991; 145: 998-1002. Lu-Yao GL, Yao SL. Population based study of long term survival in patients with clinically localised prostate cancer. Lancet 1997; 349: 906-910. Johanssen J-E, Holmberg L, Johansson S, et al. Fifteen year survival in prostate cancer: a prospective population based study in Sweden. JAMA 1997; 277: 467-471. Adolfsson J, Steineck G, Hedlund P-O. Deferred treatment of low grade prostate cancer: actual 10 year and projected 15 year follow up of the Karolinska series [abstract]. J Urol 1998; 159: 252. (Abstract No. A965.) Mettlin CJ, Murphy GP. Why is the prostate cancer death rate declining in the United States? Cancer 1998; 82: 249-251. Charatan FB. Prostate cancer screening reduces death. BMJ 1998; 316: 1626. Reprints: Clinical Associate Professor M Frydenberg, Suite 21, Cabrini Medical Centre, Isabella Street, Malvern, VIC 3144. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Mark Frydenberg · Gillian Duchesne · Phillip D Stricker

Prostate-specific antigen testing in Australia and association with prostate cancer incidence in New South Wales David P Smith and Bruce K Armstrong MJA 1998; 169: 17-20 For editorial comment, see McCredie & Cox Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To describe patterns and trends in prostate-specific antigen (PSA) testing in Australia and assess its role in the increasing incidence of prostate cancer. Design: Descriptive analysis of (i) Medicare records of PSA testing in Australia, and (ii) prostate cancer recorded incidence in New South Wales. Data: (i) Medicare data for all males who received a Medicare-reimbursed PSA test between August 1989 and December 1996. (ii) NSW Central Cancer Registry data for all males in NSW with prostate cancer diagnosed between 1988 and 1995. Main outcome measures: (i) Number of PSA tests, age-standardised rates of PSA tests by State and Territory, and proportions of males who had a PSA test. (ii) Recorded incidence of prostate cancer in NSW. Results: (i) More than 2.2 million PSA tests were done on more than 1.1 million Australians between 1989 and 1996. The annual number of males tested increased fivefold in this period and peaked in 1995. Twenty-seven per cent of Australian men aged 50 years or over had at least one PSA test in 1995 or 1996; 33% of men aged 60-69 years had a test in this period. (ii) In NSW the number of PSA tests per quarter was highly correlated with the number of new cases of prostate cancer (R2 = 0.92). Conclusions: Although no organised program for prostate cancer screening exists, and despite repeated advice against it, opportunistic screening has been occurring at high rates. There was a high correlation between PSA testing and prostate cancer incidence between 1990 and 1995 in NSW. Introduction Prostate cancer is the most common cancer in Australians after non-melanocytic skin cancers, and accounts for about a third of all newly diagnosed internal cancers in males.1,2 It is the second most common cause of cancer death among Australian males.3 During the late 1980s and early 1990s, recorded prostate cancer incidences increased substantially in Australia, while mortality from prostate cancer remained stable.1,2,4-6 Much of the increase in incidence has been attributed to detection of latent cancers by increased use of the prostate-specific antigen (PSA) test, transurethral resection of the prostate, prostatic biopsy and radical prostatectomy.7There are considerable arguments for8,9 and against10,11 screening for prostate cancer. In 1996 the Australian Health Technology Advisory Committee reviewed the evidence and recommended against screening. However, the committee recognised that de facto screening occurs in the community and stated a need to monitor and review the evidence when important developments occur.12 Data collected by the Health Insurance Commission provide the best available means to monitor trends and patterns in PSA testing. We analysed these data to determine the association between PSA testing and reported incidence of prostate cancer in Australia and in New South Wales. Methods Data PSA tests: The Commonwealth Department of Health and Family Services Medicare Estimates and Statistics Unit provided de-identified data, extracted from the national dataset of all services rendered on a fee-for-service basis for which a Medicare benefit has been paid. The data included all tests itemised under the Medicare Benefits Schedule codes that included PSA tests. PSA tests first appeared in the Schedule in August 1989, but were included with 20 "other" biochemical tests until November 1993. Since then they have been itemised together with prostatic acid phosphatase (PAP) tests. PSA tests could not be differentiated from PAP tests with the available information. To estimate the proportion of non-PSA tests in the dataset, we investigated the patterns of use of the other tests, using data provided by the Commonwealth Department of Health and Family Services. We calculated retrospective projections using exponential regression on the number of tests by age group and annual quarter to give an adjusted number of PSA and PAP tests for the period between August 1989 and November 1993. This study included data for all males who had at least one PSA or PAP test between 1989 and 1996 reimbursed by Medicare. The data included a unique identification number for each person, age, date of service, postcode, and fee charged for the service. The identification number allowed individuals to be linked over time to quantify those who had multiple tests, but was not linkable to any other identifying data. Prostate cancer: Data on prostate cancer incidence in NSW were obtained from the NSW Central Cancer Registry, a population-based register which began collecting data in 1972. Notification of malignant neoplasms has been a statutory requirement for all NSW public and private hospitals, radiation oncology departments and nursing homes since 1972, and for all pathology and outpatient departments since 1985.1 Population: The Australian Bureau of Statistics provided the estimated resident populations of Australia by five-year age group and State or Territory for the years 1989 to 1996.13 Analysis We calculated the rate of testing and the number of males tested by age group, State or Territory, and year from August 1989 to December 1996. We calculated the number of males having multiple tests from January 1995 to December 1996 and the proportion of males tested in each age group in this period. We used a two-year period for these calculations to reduce errors introduced by men moving up age groups. We compared the number of tests carried out in NSW by quarter with the number of prostate cancers diagnosed between 1990 and 1995 (the most recent year for which prostate cancer data were available). All rates, standardised to the total male and female Australian 1991 population, are expressed per 100 000 males. We used SAS software for statistical analysis.14 Results PSA testing in Australia From August 1989 to December 1996 more than 2.2 million PSA or PAP tests were reimbursed by Medicare in Australia. About 1.1 million males were tested during this period. Eighty-eight per cent of the tests were for men aged 50 years or over, with the largest proportion (34%) for men aged 60-69 years (Table 1). Age-standardised rates for males having one or more PSA/PAP tests per year increased fivefold between 1990 and 1996, and the greatest increases occurred between 1993 and 1995. There was substantial variation in the rates of testing by State and Territory (Figure 1). Except in the Australian Capital Territory, the rates peaked in 1995, when the highest rates were in Western Australia (8668 tests per 100 000) and the Australian Capital Territory (8284 tests per 100 000) and the lowest in the Northern Territory (3270 per 100 000). From January 1995 to December 1996, 709 523 Australian males had at least one PSA/PAP test reimbursed by Medicare. Most of those tested (73%) had one test, 17% had two tests, 5% had three tests and 5% had four or more tests. Older men were more likely to have had multiple tests (Table 2). In this period, 27% of Australian men aged 50 years and over had one or more PSA/PAP tests reimbursed by Medicare. This figure peaked at 33% in men aged 60-69 years (Table 3). In 1996 the Medicare schedule fee for a single PSA/PAP test was $19.90 or, where two or more tests were undertaken at the same consultation, $36.65. The overall amount reimbursed by Medicare for PSA/PAP tests in 1996 was $10 675 880 (mean per test, $20.73; mode, $19.90; range, $11.00 to $36.65), not including the fee that may have been charged for the accompanying consultation. PSA/PAP tests and prostate cancer in NSW Between 1990 and 1995, more than 625 000 PSA/PAP tests were carried out in NSW, and 20 120 prostate cancers were diagnosed. The number of tests was highly correlated with the number of prostate cancers diagnosed (R2 = 0.92) (Figure 2). The ratio of number of tests performed to number of new cases of prostate cancer diagnosed increased from about 19 in 1990 to 45 in 1995. In 1995, in NSW, 150 479 males had one or more PSA/PAP tests. Figure 3 shows the age-specific rates of testing and reported incidence of prostate cancer. The number of PSA/PAP tests per prostate cancer detected in 1995 varied between age groups from a high of 579 in men aged 40-49 years to fewer than 24 in men aged 70 years or over. Discussion More than 2.2 million PSA tests were carried out in Australia from 1989 to 1996. More than 1.1 million males were tested in this period, and the annual number of males tested peaked in 1995. Data from this study support the hypothesis that the rising incidence of prostate cancer is associated with increased PSA testing. In NSW, the number of PSA tests was highly correlated with the number of new cases of prostate cancer. The PSA test is a blood test used in diagnosis and monitoring of prostate disease. First used in Australia in the late 1980s to monitor clinically identified disease, it has since been used in the diagnosis of relevant symptoms and as a screening test for asymptomatic men. It was not possible to identify from Medicare data the reasons why the tests were ordered. However, recent research found that 67 of 118 PSA tests (57%) were ordered for screening.15 Although we adjusted for other tests included under the same Medicare Benefits Schedule item from 1989 to 1993, we could not adjust for PAP tests, which are used to monitor the clinical progress of prostate cancer. However, in a continuous six-month period the ratio of PAP tests to PSA tests processed by a large, representative private pathology laboratory in NSW (covering city, suburban and regional centres) was less than 2% (Dr G Caldwell, Pathologist, Douglass Hanly Moir Pathology, personal communication). Data from a large public pathology laboratory in South Australia indicate that the proportion of PAP tests to the total PSA and PAP tests fell from 50% in 1991 to 6% in 1996 (Dr H A Morris, Manager, Endocrine Unit, Institute of Medical and Veterinary Science, personal communication). At their peak in 1995, the rates of PSA/PAP testing in Australian males ranged from 3270 per 100 000 in the Northern Territory to 8668 per 100 000 in Western Australia. These are probably underestimates because Medicare data do not include services provided free to public patients in public hospitals, to Veterans' Affairs patients and to men offered screening under the research activities of centres such as the Perth-based Urological Research Centre. In the one-year period April 1993 to March 1994, 39 626 PSA tests were done on 30 739 veterans.16 Data from the Department of Veterans' Affairs show about 50 000 tests were done each year in Australia between 1994 and 1996, which would have contributed a further 10% to the number of Medicare-reimbursed PSA tests. In South Australia 72 000 PSA tests that would not appear in Medicare statistics were undertaken between 1990 and 1996 by a public laboratory (Dr H A Morris, personal communication). These and the tests done on veterans would have accounted for an approximate under-enumeration of 33% annually in South Australia. Nationally, considering all these extra sources of PSA tests, we estimate that Medicare data underenumerate PSA tests by 14%. In a recent study of self-reported rates of prostate cancer screening in the Central Sydney Area Health Service, about one in five men aged 50 years or over reported being screened in the previous 12 months.17 This agrees quite closely with our results, which show that during the two years 1995 to 1996 about one in four Australian men aged 50 years or over had a PSA test, and in 1995 one in six (17%) had a test. More prostate cancers would result in more PSA tests used for monitoring. However, the overall effect of this on PSA test-ordering is thought to be small. More than 70% of males tested in 1995 and 1996 had only one test, suggesting that most tests were for screening rather than monitoring disease activity. A further possible indication that most tests were undertaken for screening rather than for monitoring or diagnosis is the increase in the ratio of tests to newly diagnosed prostate cancers in New South Wales. This ratio continued to increase in 1995, when the reported incidence of prostate cancer had begun to fall. Increasing recorded incidences of prostate cancer have been reported from the United States,18-22 France23 and elsewhere in Australia.1,2,4-6 Incidence figures began rising earlier in the United States than in Australia, and appeared to peak in 1992 and 1993.20 South Australian and Western Australian age-standardised recorded incidences peaked in 1994 and fell by 22% and 13%, respectively, between 1995 and 1996.2,4,5 The rate of PSA testing peaked in 1995 in both States and fell 10% and 16%, respectively, in 1996. These data and the high correlation between PSA tests and newly diagnosed prostate cancers in NSW support the hypothesis that the rising incidence figures for prostate cancer in the early 1990s were a direct result of screening.7 Based on these trends and correlations, it is likely that the recorded incidence for prostate cancer in most Australian States and Territories will continue to fall after 1995. Given that screening for prostate cancer has never been recommended in Australia, the rates of de facto screening in men aged over 50 years, and especially those aged between 60 and 69 years, are quite remarkable. These findings have important implications for public health policy and for patient and practitioner education aimed at reducing prostate cancer screening. Acknowledgements We would like to thank Mr Ross Saunders, Director of the Medicare Statistics Section of the Department of Health and Family Services, for supplying the data. References Coates M, Armstrong B. Cancer in New South Wales. Incidence and mortality 1994. Sydney: NSW Cancer Council, 1997. South Australian Cancer Registry. Epidemiology of cancer in South Australia. Incidence, mortality and survival 1977 to 1996, incidence and mortality 1996 analysed by type and geographical location. Twenty years of data. Adelaide: South Australian Health Commission, 1997. Australian Bureau of Statistics. Causes of death, Australia, 1995. Canberra: AGPS, 1996. (Catalogue No. 3303.0.) Threlfall T, Whitford M, Thompson J. Cancer incidence and mortality in Western Australia 1992 to 1994. A report of the Western Australian Cancer Registry. Perth: Health Department of Western Australia, 1996. Threlfall T, Thompson J. Cancer incidence and mortality in Western Australia, 1995. A report of the Western Australian Cancer Registry. Perth: Health Department of Western Australia, 1997. Shugg D, Dwyer T, Blizzard L. Cancer in Tasmania. Incidence and mortality 1994. Hobart: Menzies Centre for Population Health Research, 1997. McCredie M, Coates M, Churches T, Rogers J. Rising incidence of prostate cancer in Australia: a result of 'screening'? J Epidemiol Biostatistics 1996; 1: 99-105. Lange PH. Is screening for prostate cancer the current gold standard? -- "Yes". Eur J Cancer 1997; 33: 354-356. Kaye KW. Prostate cancer: enthusiasm for screening. Med J Aust 1995; 162: 540-541. Kramer BS, Gohagan JK, Prorok PC. Is screening for prostate cancer the current gold standard? -- "No". Eur J Cancer 1997; 33: 348-353. Hirst GHL, Ward JE, Del Mar CB. Screening for prostate cancer: the case against. Med J Aust 1996; 164: 285-288. Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. Australian Bureau of Statistics. Estimated resident population by sex and age: States and Territories of Australia 1996. Canberra: Australian Bureau of Statistics, 1997. (Catalogue no. 3201.0.) SAS [computer program]. Version 6.12. Cary, North Carolina: SAS Institute, 1996. Ward JE, Gupta L, Taylor NJ. Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer? Med J Aust 1998: 169; 29-31. Parkes AJ, Killer GT. Prostate-specific antigen -- is it already being used as a screening test? [letter]. Med J Aust 1994; 161: 722-723. Ward JE, Hughes A-M, Hirst GHL, Winchester L. Men's estimates of prostate cancer risk and self-reported rates of screening. Med J Aust 1997; 167: 250-253. Stephenson RA, Smart CR, Mineau GP, et al. The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence -- data from the Utah Cancer Registry. Cancer 1996; 77: 1342-1348. Jacobsen SJ, Katusic SK, Bergstralh EJ, et al. Incidence of prostate cancer diagnosis in the eras before and after serum prostate-specific antigen testing. JAMA 1995; 274: 1445-1449. Merrill RM, Potosky AL, Feuer EJ. Changing trends in U. S. prostate cancer incidence rates. J Natl Cancer Inst 1996; 88: 1683-1685. Gann PH. Interpreting recent trends in prostate cancer incidence and mortality. Epidemiology 1997; 8: 117-120. Lu-Yao GL, Greenberg R. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Menegoz F, Colonna M, Exbrayat C, et al. A recent increase in the incidence of prostatic carcinoma in a French population: role of ultrasonography and prostatic specific antigen. Eur J Cancer 1995; 31A: 55-58. (Received 28 Nov 1997, accepted 24 Apr 1998) Authors' details Cancer Control Information Centre, New South Wales Cancer Council, Sydney, NSW. David P Smith, BA, MPH, Research Coordinator, Cancer Epidemiology Research Unit; Bruce K Armstrong, DPhil, FRACP, Director. Reprints will not be available from the authors. Correspondence: Mr D P Smith, Cancer Epidemiology Research Unit, NSW Cancer Council, PO Box 572, Woolloomooloo, NSW 2011. E-mail: dsmithATnswcc.org.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

David P Smith · Bruce K Armstrong

Prostate cancer in Western Australia: trends in incidence and mortality from 1985 to 1996 Timothy J Threlfall, Dallas R English and Ian L Rouse MJA 1998; 169: 21-24 For editorial comment, see McCredie & Cox Abstract - Introduction - Methods - Results - Discussion - References - Addendum - Authors' details - - ©MJA1998 Abstract Objective: To measure trends in recorded incidence and mortality rates of prostate cancer in Western Australia from 1985 to 1996 and to relate these to prostate-specific antigen (PSA) testing for prostate cancer. Design: Descriptive study based on data from the Western Australian Cancer Registry, the Australian Bureau of Statistics and the Health Insurance Commission. Data: All newly diagnosed cases of prostate cancer and all deaths from prostate cancer in Western Australia from 1985 to 1996. Main outcome measures: Recorded incidences and mortality rates for prostate cancer. Results: After increasing steadily from 42 per 100 000 person-years in 1985 to 61 in 1992, the recorded incidence more than doubled to 134 per 100 000 person-years in 1994, then fell sharply to 87 in 1996. Among men aged 50 years or more, those aged 50-54 years had the largest annual increases: 14% (95% confidence interval [CI], 10%-19%) from 1985 to 1992 and 108% (95% CI, 84%-134%) from 1992 to 1994. They also had the smallest annual decline between 1994 and 1996 (8%; 95% CI, 1% increase to 16% decrease). The mortality rate showed no sudden increases or decreases. In men aged 60 years or older, the mortality rate increased annually by 2.9% (95% CI, 2%-4%) from 1985 to 1996. The number of Medicare reimbursements for PSA tests increased until May 1995, then fell. There was a significant correlation between the monthly number of PSA tests and new cases of prostate cancer (P < 0.01). Conclusions: Following a period of steady increase, the recorded incidence of prostate cancer increased dramatically in 1992 because of screening by PSA testing. From 1994, these incidence figures declined almost as sharply, partly because of reductions in testing. The mortality rate has not shown any systematic deviation from its long-term trend. Introduction In the early 1990s the recorded incidence of prostate cancer increased dramatically in Australia,1,2 several years after a similar increase in the United States.3-7 Testing for the disease among asymptomatic men by measuring plasma prostate-specific antigen (PSA) is believed to be responsible for the increases.1,3,4,7We report here on trends in incidence figures and in the mortality rate for prostate cancer in Western Australia from 1985 to 1996, and their relationship to PSA testing. Methods Data sources We obtained data on prostate cancer cases and deaths from the Western Australian Cancer Registry, and population estimates from the Australian Bureau of Statistics (ABS).8 We standardised rates to the World Standard Population and calculated the risk of men developing prostate cancer before the age of 75 years.9 Because mortality rates based on coding of cause of death by the ABS were not available for 1996, we used 1996 rates from the Registry, which began coding causes of death in 1990; from 1990 until 1995, the two mortality rates were almost identical. Data relating to the number of PSA tests reimbursed by Medicare in Western Australia were obtained from the Health Insurance Commission in July 1997. Socioeconomic status To investigate any effect of socioeconomic status (SES) on recorded incidence we used an index, derived from the 1991 census, in which each census collection district (about 50 households) is assigned a score.10 For Perth patients, addresses at the time of diagnosis were mapped to collection districts for the 1991 census using MapInfo.11 Geographical coordinate data were provided by the Western Australian Valuer General's office and the Department of Land Administration. The SES index was divided into quarters of its distribution. Because population data were available at the collection district level for census years only (ie, 1986 and 1991), we could not calculate SES-specific incidence. To determine whether any changes in numbers of cases by SES might be the result of different changes in population size in areas of different SES, we compared numbers of cases of prostate cancer and lung cancer. Trends in age-specific rates We used Poisson regression in EGRET12 to model age-specific recorded incidences and mortality rates. Analyses of incidence were restricted to men aged 50 years or older and analyses of mortality rate to men aged 60 years or older because there were few events in younger age groups. We analysed recorded incidence for each of the periods January 1985 to December 1992, January 1992 to December 1994 and January 1994 to December 1996. (Because the periods overlap, the results were not independent.) A single analysis of mortality rate was conducted. Likelihood ratio tests were used to obtain P values. We fitted age group as a categorical (ie, factored) variable and year of diagnosis as a continuous variable. The coefficient for year was exponentiated to give an annual percentage increase in the rate (eg, a coefficient of 0.35 when exponentiated is 1.42, equivalent to an annual increase of 42%). Age was added first, followed by the year of diagnosis, and then the interaction between the two. The interaction was fitted with age as a categorical variable and as a continuous variable, and the difference between these models was tested. Fitting the interaction with age as a categorical variable tests whether the secular trend was the same for all age groups; fitting it with age as a continuous variable tests whether there was a greater increase in younger men than in older men (or vice versa). In the analyses of incidence, P values for comparison of the two types of interaction were 0.17 for 1985-1992, 0.32 for 1992-1994 and 0.70 for 1994-1996. As there were no significant differences, the results reported for recorded incidence are from models in which the interaction involved age as a continuous variable. In all analyses, the final models provided good fits to the data -- the smallest P value for goodness-of-fit (for incidence in the period 1992-1994) was 0.09. Prostate-specific antigen testing Medicare began identifying PSA tests, together with prostatic acid phosphatase (PAP) tests, as a separate item during November 1993. Fewer than 1% of these tests would be PAP tests (Dr Glen Edwards, Chemical Pathologist, Western Diagnostic Pathology, personal communication). We plotted the number of tests reimbursed by Medicare each month from December 1993 to December 1996. To investigate the trends in the numbers of tests, we fitted a curve through the data. Results Incidence From 1985 until 1992, the age-adjusted recorded incidence increased steadily from 42 to 61 per 100 000 person-years (Figure 1). In the next two years it more than doubled to 134 per 100 000 person-years, but then fell almost as sharply to 87 in 1996. The risk of prostate cancer before age 75 years was one in 23 in 1985, one in six in 1994 and one in nine in 1996. Age: In men aged over 50 years, the recorded incidence of prostate cancer increased annually by 5% (95% confidence interval [CI], 3%-6%) between 1985 and 1992 (trend, P < 0.001). The largest relative increases in recorded incidence between 1985 and 1992 occurred in the youngest men (Table 1; interaction between year and age, P < 0.001). The largest relative increases between 1992 and 1994 were also seen in the younger age groups (interaction between year and age, P < 0.001), and from 1994 to 1996 the decline was greatest in the oldest men (interaction between year and age, P < 0.001). As a result of the different relative changes in different age groups, the differences in age-specific rates in 1996 were smaller than in earlier years. In 1985, the recorded incidence for men in the oldest age groups was close to 1000 times higher than for men aged 50-54 years, but by 1996 the relative difference was about 100-fold. We also examined the absolute changes in recorded incidence between 1992 and 1996 (Table 2). Between 1992 and 1994, the largest absolute increases were in men aged 65-79 years. Between 1994 and 1996, the largest absolute decreases were in men aged 70 years or older, so that between 1992 and 1996 the overall increases were greatest in men aged 60-69 years. The overall changes in men aged 55-59 years and 70-74 years were similar. The mean age at diagnosis was 73 years in 1985, 74 years from 1986 until 1990, 73 years in 1991 and 1992, 72 years in 1993, 70 years in 1994 and 69 years thereafter. Place of residence: We examined age-standardised recorded incidence for prostate cancer separately for the Perth metropolitan region and the rest of Western Australia. Before 1992, the two rates were similar in all years. During the sudden rise and fall, these incidences were, respectively, 1992: 65 per 100 000 person-years (Perth), 51 per 100 000 person-years (non-metropolitan areas); 1993: 141 per 100 000 person-years, 107 per 100 000 person-years; 1994: 141 per 100 000 person-years, 110 per 100 000 person-years; 1996: 87 per 100 000 person-years, 84 per 100 000 person-years. Socioeconomic status: We mapped 94% of lung cancer and prostate cancer cases in the Perth metropolitan area to a 1991 census collection district, with no apparent trend over time in the proportion mapped. Before 1993, the numbers of prostate cancer cases in the four SES groups were similar (Figure 2). However, the increase in cases in 1993 and 1994 was greatest in areas of highest SES, and the largest declines in numbers of cases from 1994 to 1996 were also in these areas. Over the same period, there was no consistent change in the distribution of lung cancer cases by SES (Figure 2). Mortality rate The age-adjusted mortality rate from 1985 to 1996 showed no sudden increases or decreases (Figure 1). In men aged 60 years or older, the estimated annual increase from 1985 to 1996 was 2.9% (95% CI, 2%-4%; trend, P < 0.001). Adding quadratic (P = 0.78) or cubic (P = 0.92) terms for year did not improve the fit of the Poisson model. Furthermore, models using year as a continuous or a categorical variable fitted equally well (P = 0.14), indicating that year-to-year variations in the trend of the age-adjusted rates could be a result of chance alone. The increase differed across age groups (interaction between age as a categorical variable and year of death, P = 0.03), but the trends by age were inconsistent (Table 1; interaction between age as a continuous variable and year of death, P = 0.96). Prostate-specific antigen testing On average, there were 5337 tests reimbursed each month in Western Australia. The numbers of tests initially increased before falling, although there was substantial monthly variation (Figure 3). A cubic curve fitted the data well (R2 = 0.46) and provided a better fit than a quadratic curve (P < 0.001) or a linear model (P < 0.001). The fitted maximum monthly number of tests occurred in May 1995. Spearman's rank correlation between the monthly number of PSA tests and new cases of prostate cancer was 0.48 (P < 0.01). Discussion After increasing steadily during the 1980s, the age-adjusted recorded incidence of prostate cancer more than doubled between 1992 and 1994. By 1996, it had fallen to a level about 40% higher than that in 1992. In contrast, the mortality rate increased by about 3% per year, with no sudden increases or decreases. The youngest age groups showed the largest relative increases in recorded incidence up to 1994, and the oldest age groups showed the greatest decrease after 1994, causing a substantial compression of the range of age-specific recorded incidence in Western Australia. When the rates rose steeply in 1992, the absolute increases were greatest in men aged 65-79 years. However, men aged 70 years or older had the greatest absolute falls from 1994, so that, between 1992 and 1996, the largest absolute increases were in men aged 60-69 years. The increase appeared first in Perth and the peak was higher in Perth. However, by 1996, Perth and the rest of Western Australia had similar recorded incidences of prostate cancer. Within Perth, the changes were greatest in areas of high SES. Most observers have attributed the increases in recorded incidence of prostate cancer during the 1980s to improved case detection, particularly following transurethral resection of the prostate for benign prostatic hypertrophy.1,13 The sudden rise in incidence figures in about 1993 was observed in all Australian States.1 In the United States, similar dramatic increases were observed first in 1989.3 These increases are almost certainly the result of the introduction of screening by PSA testing.1,3 In Western Australia, free PSA testing during Prostate Awareness Week would have contributed to the increase. Each October from 1993, about 1100 men attended Prostate Awareness Week in Perth for PSA tests (Mr M D'Antuono, Biostatistician, Urological Research Centre, University of Western Australia, personal communication). These tests do not appear in the Medicare figures, although the peaks in Medicare-funded PSA tests in November 1994 and November 1995 might be the result of publicity surrounding Prostate Awareness Week. However, substantially fewer tests were performed at the screening venues than were reimbursed by Medicare each month in Western Australia. Thus, Prostate Awareness Week is unlikely to have greatly increased the recorded incidence in Western Australia. Rapid declines in recorded incidence, such as we found in Western Australia since 1994, have also been reported in some US States.4,6,7,14 Part of the Western Australian decrease is probably the result of reduced screening activity. The most likely explanation for the decrease in Medicare reimbursements that started in 1995 is a reduction in PSA testing for screening. In fact, the reduction in screening tests is probably greater than Figure 3 suggests, because PSA testing is also used for surveillance of men with prostate cancer. Therefore, its overall use will decline less rapidly than its use for screening. Widespread publicity in the media about the controversy surrounding screening for prostate cancer may have contributed to this decline, and the greater declines seen in the oldest men may be because of concerns that screening is unlikely to benefit those with a short expectation of life.15 Recorded incidence is expected to decrease even if screening activity remains constant. After the introduction of screening, recorded incidence increases because the time of diagnosis is advanced and some cases may be diagnosed that would not have become symptomatic. When all prevalent cases are detected, incidence figures will fall until new cancers develop, whereupon they will rise again. If screening detects only those cancers that would eventually have been diagnosed anyway, the recorded incidence will stabilise at its pre-screening level. Otherwise, it will stabilise at a higher level.16 Before 1980, the mortality rate from prostate cancer in Australia was stable for some time.17 Since then it has increased, but more slowly than recorded incidence, indicating that short-term survival, at least, has improved over time. Increasing diagnosis of disease with low potential for metastasis is one explanation for the discrepancy. What changes in mortality rate can we expect? Gann has argued that if screening is effective and covers enough of the population, the mortality rate should eventually decrease.16 It is too early for any effect of screening on mortality rate to be seen, and by the end of 1996 there had been no new trend in the mortality rate in Western Australia. Because of the effect of lead time (the time by which screening advances diagnosis), changes may not occur for some years. We have witnessed extraordinary changes in the recorded incidence of prostate cancer in Western Australia, and we have strong evidence that these changes are the result of medical practice rather than intrinsic changes in the incidence. Surveillance of incidence and mortality rates may help answer the question of whether screening has benefit, although more rigorous scientific evaluations are also needed. References McCredie M. A rising incidence of prostate cancer in Australia: effect of "screening" or more disease? Cancer Forum 1995; 19: 7-12. McCaul KA, Luke CG, Roder DM. Trends in prostate cancer incidence and mortality rates in South Australia, 1977-1993. Med J Aust 1995; 162: 520-522. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Gilliland FD, Welsh DJ, Hoffman RM, Key CR. Rapid rise and subsequent decline in prostate cancer incidence rates for New Mexico, 1989-1993. Cancer Epidemiol Biomarkers Prev 1995; 4: 797-800. Merrill RM, Brawley OW. Prostate cancer incidence and mortality rates among white and black men. Epidemiology 1997; 8: 126-131. Polednak AP. Trends in prostate carcinoma incidence in Connecticut (1988-1994) by age and race. Cancer 1997; 79: 99-103. Newcomer LM, Stanford JL, Blumenstein BA, Brawer MK. Temporal trends in rates of prostate cancer: declining incidence of advanced stage disease, 1974 to 1994. J Urol 1997; 158: 1427-1430. Australian Bureau of Statistics. Estimated Resident Population by age and sex in statistical local areas, Western Australia. Canberra: AGPS, 1996. (Catalogue No. 3203.5.) Parkin DM, Muir CS, Whelan SL, et al, editors. Cancer incidence in five continents. Vol VI. IARC Scientific Publications No. 120. Lyon: International Agency for Research on Cancer, 1992. Australian Bureau of Statistics. Information Paper: 1991 Census socioeconomic indicators for areas. Canberra: AGPS, 1993. (Catalogue No. 2912.0.) MapInfo [computer program]. Version 3. New York: MapInfo Corporation, 1995. EGRET [computer program]. Version 1.02. Seattle: Statistics and Epidemiology Research Corporation, 1995. Potosky AL, Kessler L, Gridley G, et al. Rise in prostatic cancer incidence associated with increased use of transurethral resection. J Natl Cancer Inst 1990; 82: 1624-1628. Stephenson RA, Smart CR, Mineau GP, et al. The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence -- data from the Utah Cancer Registry. Cancer 1996; 77: 1342-1348. Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994; 330: 242-248. Gann PH. Interpreting recent trends in prostate cancer incidence and mortality. Epidemiology 1997; 8: 117-120. Holman CD, James IR, Segal MR, Armstrong BK. Recent trends in mortality from prostate cancer in male populations of Australia and England and Wales. Br J Cancer 1981; 44: 340-348.(Received 30 Sep 1997, accepted 31 Mar 1998) Addendum Since this article was submitted in September 1997, data on the recorded incidence and mortality rate of prostate cancer in the first eight months of 1997 have become available. The age-adjusted recorded incidence of prostate cancer was 64 per 100000 person-years, while the mortality rate was 16 per 100000 person-years. Thus, the recorded incidence was almost the same as in 1992, before the rapid rise and fall. In 1997, men aged 50-69 years had higher recorded incidences of prostate cancer than in 1992, but older men had lower recorded incidences. Authors' details Health Department of Western Australia, East Perth, WA. Timothy J Threlfall, MB BS, MPH, Senior Medical Officer, Western Australian Cancer Registry; Ian L Rouse, PhD, General Manager, Health Information Centre. Department of Public Health, University of Western Australia, Nedlands, WA. Dallas R English, PhD, Senior Lecturer. Reprints: Dr D R English, Department of Public Health, University of Western Australia, Nedlands, WA 6907. E-mail: dallasATdph.uwa.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Timothy J Threlfall · Dallas R English · Ian L Rouse

Self-reported prevalence of prostate-specific antigen testing in South Australia: a community study Carole B Pinnock, David P Weller and Villis R Marshall MJA 1998; 169: 25-28 For editorial comment, see McCredie & Cox Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the prevalence and other characteristics of self-reported blood testing (prostate-specific antigen [PSA]) for prostate cancer in the community. Design: Interview-based prevalence study. Participants and setting: 695 men aged 40 years and over in the Spring 1996 South Australian Health Omnibus survey of a probability sample of 3011 households, weighted to reflect the age and sex distribution of the South Australian population. Outcome measures: Number of men who had a PSA test in the preceding 12 months; number of first tests; the person initiating and performing the test; knowledge of the next step if test result abnormal; number of men visiting doctor for lower urinary tract symptoms in the preceding 12 months. Results: 20.3% of participants reported having a PSA test in the preceding 12 months; 62.1% were first tests. Prevalence of testing was highest in the age group 70-79 years (35.8%). Most tests were initiated by the general practitioner (41.2%) and by patients (35.7%). Of those tested, 45.3% had inadequate knowledge of the next step. Visiting a doctor for urinary symptoms was significantly associated with PSA testing (P < 0.001): 47.7% of men who visited a doctor for urinary symptoms had been tested compared with only 17.4% of those who did not visit the doctor for this problem. Only age and visiting a doctor for urinary symptoms were significant independent predictors of having a PSA test. Conclusions: Investigation of lower urinary tract symptoms contributed substantially to PSA testing, and those tested did not adequately understand the consequences. Our findings suggest a need for a better framework for PSA testing in general practice, including all important elements of decision-making, such as evidence and patient preference, as well as the means to ensure adequate patient counselling before testing. Introduction Screening for prostate cancer remains a topic of widespread debate. Recent systematic reviews have concluded that there is currently insufficient evidence to establish an overall benefit of prostate cancer screening, and major health agencies have issued conflicting recommendations.1-3 Randomised controlled trials examining this question have begun in the United States and Europe,4,5 but results will not be available for some years. Nevertheless, prostate-specific antigen (PSA) testing of asymptomatic men is thought to be common in Australia,6,7 and the recent doubling in recorded incidence of prostate cancer in this country8,9 has been attributed to PSA testing. Little is known about the circumstances of such testing -- whether it occurs in general practice or other specialties, whether men are truly asymptomatic, whether the test is initiated by the patient or the doctor, and how much information about the test is provided to the patient. Most authors agree that men seeking a test should be informed about the risks as well as the benefits of taking the test,10,11 and that individual preferences should be taken into account.12-15 A community survey of self-reported participation in PSA testing confirmed high rates in the community (25% of men 40 years and over with no history of prostate cancer) and an even higher rate of intention to test (53.9%).16 The strongest predictor of past testing was a visit to a doctor for urinary tract symptoms, and the strongest predictor of intention to test was perceived vulnerability to prostate cancer.16 This study was undertaken in 1996 to expand these findings by establishing the prevalence of self-reported prostate cancer testing (PSA testing) over the preceding 12 months, the incidence of PSA testing (first tests), who initiated the test, who performed it, the association with investigation for urinary symptoms, and whether participants had understood the immediate consequences of taking the test. Methods Survey Questions were included in the Spring 1996 South Australian Health Omnibus survey, a multiple-user household interview survey undertaken on behalf of a number of healthcare organisations in South Australia. The sampling method provides a probability sample of the South Australian population.17,18Participants were asked whether they had visited the doctor for troublesome urinary symptoms in the past 12 months (as in a previous survey17), ever been diagnosed with prostate cancer or had a blood test for prostate cancer (PSA test) in the previous 12 months. Those who had been tested were asked who had initiated the test, who performed it and what they understood to be the next step if the test were abnormal. Question alternatives were derived from a previous qualitative study (who initiated test)19 and expert clinical opinion (who performed it, next step). Questions were tested for comprehensibility and acceptability in 50 pilot interviews before the survey. Analysis Data were weighted by household size, age, sex and geographical region to benchmarks derived from the estimated resident population at 30 June 1995 (Australian Bureau of Statistics). Because of the clustered nature of the sample, confidence limits were calculated after allowing for a design effect of 1.1, calculated using the method of Kish,20 which inflates the standard error. We analysed data for men aged 40 years or older who had not had a diagnosis of prostate cancer, using SPSS for Windows.21 Statistical significances were determined by Pearson c2 tests or Fisher's exact test, and logistic regression by the forced entry method (the contribution is evaluated after removal of effects of all other variables). The contribution of demographic and urinary symptom variables was examined in a logistic regression model to identify independent predictors of having a PSA test in the preceding 12 months. Results Sample In unweighted numbers, from the sampling frame of 4081 households, 3011 interviews were conducted, giving a response rate of 73.8%. The reasons for not participating were refusal (548), no contact could be established (301), selected respondent away for duration of study (108), illness/mental incapacity (65) and respondent unable to speak English (48). Of the 3011 people interviewed, 695 were men 40 years or older and 642 of these had not had a diagnosis of prostate cancer. The average age of these 642 men was 58.3 years (SE, 0.50 years; range, 40-91 years). After weighting, 6.0% (95% confidence interval [CI], 4.45%-7.86%) of men aged 40 years or more reported being diagnosed with prostate cancer. The weighted sample size of men aged 40 years and over with no reported diagnosis of prostate cancer was 716. PSA testing and demographic factors Overall, 20.3% of men older than 40 years reported having a blood test for prostate cancer (PSA test) in the preceding 12 months (Table 1). This varied with age (chi-squared = 48.1; df = 4; P < 0.001), with the highest proportion (35.8%) being in the age group 70-79 years. Nearly two-thirds of tests (62.1%) were first tests, and this proportion was high across all age groups. Men were slightly more likely to be tested if they lived in metropolitan (20.8%; 95% CI, 17.5%-24.1%) than in rural (19.0%; 95% CI, 15.8%-22.1%) areas, but the difference was not significant. Educational attainment was not associated with testing. Lifetime occupation also showed no clear trends (eg, drivers and plant operators had similar rates to managers and administrators), nor did marital status and country of birth. Lower urinary tract symptoms Of 715 men aged 40 years and over who had not had a diagnosis of prostate cancer, 65 (9.1%) had visited a doctor for troublesome lower urinary tract symptoms (LUTS) in the preceding 12 months (46 visited their general practitioner). Of these 65 men, 31 (47.7%) had had a PSA test, compared with only 113/650 (17.4%) of those who did not visit the doctor for such a problem (P < 0.001, Fisher's exact test). A first visit to a doctor for LUTS was significantly associated with a first PSA test (P = 0.018, Fisher's exact test): 15/17 (88.2%) men who had a first visit for LUTS in the previous 12 months also had a first test in that time, compared with only 6/14 (42.9%) men for whom it was not the first visit. Who initiates and performs the test Most testing (70.6%) was performed in general practice, and most tests were initiated by the general practitioner (Table 2). However, patients initiated 35.7% of tests. Tests performed by "other doctor" may reflect those done by pathology services, but could also have been included in other types of medical assessments. Doctors initiated 25 (80.6%) of the tests on the 31 men who visited for LUTS and were tested, but initiated only 51 (45.1%) of the tests on the 113 who were tested but had not visited a doctor for LUTS (chi-squared = 12.3; df = 1; P < 0.001). Knowledge of the "next step" There was wide variability in understanding of the next step if the test were abnormal. The most frequent response was "do not know" (34.0%). Other responses were "operation on the prostate" (10.7%), "no further action" (0.6%), "referral to a specialist" (27.2%), "repeat the test" (6.3%), "biopsy of the prostate" (4.8%) and "other" (16.7%). The first three (do not know, operation on the prostate, no further action), totalling 45.3%, may be considered to reflect poor understanding. Independent predictors of testing The logistic regression model (chi-squared = 89.8; df = 22; P < 0.001) included age, rural/metropolitan residence, country of birth, educational attainment, marital status, lifetime occupation, and doctor visit for LUTS in the past 12 months. Of these, only age and visit to a doctor for LUTS were significant independent predictors of having had a PSA test in the past 12 months (Table 3). Discussion We found a high level of self-reported PSA testing among men in South Australia. Testing was associated with lower urinary tract symptoms and was initiated by the patient or his GP. Nearly half the respondents had an inadequate knowledge of the appropriate next step if the test result were abnormal. Our study was a community-based survey of self-reported testing. Such studies suffer from limitations in that individual recall of past events and comprehension of the research questions may vary. Nevertheless, representative community sampling makes it possible to derive estimates of incidence and prevalence, a benefit over general practice-based studies. The level of self-reported rates of PSA testing observed in this study is higher than that reported in New South Wales across all age groups.7 This may result from a real difference between South Australia and New South Wales or from differences in survey method. The sampling method differed between the two studies (probability sample weighted to reflect age and sex structure of South Australian population versus random telephone number selection from Sydney metropolitan white pages). Older men were under-represented in the New South Wales study compared with 1991 Census data. The interview method (face to face in South Australia versus telephone in New South Wales) may also have contributed to the differences. In our study, the number of men tested increased with age and peaked in the age group 70-79 years, with nearly half the tests in this age group being first tests. The choice to begin PSA testing at this age is of concern, as those least likely to benefit are men who can anticipate less than a decade of life.1 We found no association between PSA testing and socioeconomic factors such as education and occupation, although in the United States participation in prostate cancer screening is reported to be sensitive to socioeconomic factors.22,23 However, our result is consistent with other Australian data.7,16 It is also consistent with the view that testing is initiated more by doctors than patients in this community. There was only a small difference between rural and metropolitan testing rates, which suggests that access to services does not influence the number of men seeking or being offered testing. The role of LUTS in prompting testing for prostate cancer has been reported previously,7 and is important because of the high prevalence of such symptoms in the community. In a recent South Australian survey, 26.4% of men over 18 years reported experiencing troublesome urinary symptoms in the past 12 months, and 10.2% had visited a doctor for this reason. A similar number (8.6%) were substantially dissatisfied with their urinary function.17 The relative proportions of men and their doctor initiating prostate cancer testing have not been reported previously. We found that, in the absence of urinary symptoms, this is roughly equal. However, among those men who had visited a doctor for LUTS, 80% of tests were doctor-initiated. This strong association between doctor as test initiator and LUTS suggests that, while testing may be for case-finding or screening purposes in asymptomatic men, its use may be investigational for those with LUTS. We cannot know, from these and other data,7 whether other indicators for investigational PSA testing (such as abnormal or suspicious digital rectal examination, family history of prostate cancer, or complicated LUTS) were present, and therefore whether testing was appropriate in these cases. The current clinical guidelines for uncomplicated LUTS do not recommend testing for prostate cancer.24 The American College of Physicians maintains that, as no association between LUTS and prostate cancer has been demonstrated, testing in men both with and without LUTS consistent with benign prostatic enlargement constitutes screening.10 Current guidelines focus on when not to use the PSA test, but not when it is appropriate.24 There is no framework for doctors and patients which includes all the important elements of decision-making in this area, including evidence, patient preference and medicolegal issues. PSA testing in general practice is driven in part by concern of patients and in part for investigational purposes. In addition, there is anecdotal evidence that general practitioners are concerned that if a PSA test is not offered, and prostate cancer is later diagnosed, they may be seen as negligent. Clinical guidelines or other measures promoting the appropriate use of the PSA test in general practice need to give consideration to all of these factors. Undoubtedly, providing information about testing for prostate cancer is more complex than for breast cancer or cervical cancer screening. The finding that a large proportion of men tested did not understand the immediate consequences of testing is thus not surprising, but of concern. We cannot tell from these data whether information was not given, not understood, or not recalled. Nevertheless, it is reasonable to assume that if this very basic information is not understood effectively, then more complex information (such as the likelihood of a false positive result, side effects of a biopsy, effectiveness of treatment for early-stage prostate cancer, and the risks of impotence and incontinence resulting from radical surgery for localised cancer) would also not have been understood. Yet this has been suggested as basic information needed by a patient to understand the implications of a PSA test.11,14,15 We therefore see a need for closer examination of the exchange and uptake of information in consultations that result in a PSA test, and the provision of resources for GPs which aid effective counselling. Such resources may need to include longer consultations. Acknowledgements The study was funded through a collaboration of Repatriation General Hospital, Daw Park, the Anti-Cancer Foundation of Australia, and the Department of Evidence Based Care and General Practice, Flinders University of South Australia, under the auspices of the Collaborative Centre for Prostate Health. References Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. National Health Service. Screening for prostate cancer: effectiveness matters. York, UK: NHS Centre for Reviews and Dissemination, 1997. Mettlin C, Jones G, Avarette H, et al. Defining and updating the American Cancer Society guidelines for cancer-related checkup: prostate and endometrial cancers. CA Cancer J Clin 1993; 43: 42-46. Denis L, Middelheim A. To screen or not to screen? Prostate 1992; Suppl 4: 63-70. Gohagan J, Prorok P, Kramer B, et al. The prostate, lung, colorectal and ovarian screening trial of the National Cancer Institute. Cancer 1995; 75: 1869-1873. Parkes A, Killer G. Prostate-specific antigen -- is it already being used as a screening test? [letter]. Med J Aust 1994; 161: 722-733. Ward JE, Hughes A-M, Hirst GHL, Winchester L. Men's estimates of prostate cancer risk and self-reported rates of screening. Med J Aust 1997; 167: 250-253. McCredie M. A rising incidence of prostate cancer in Australia: effect of "screening" or more disease? Cancer Forum 1995; 19: 7-12. McCaul K, Luke C, Roder D. Trends in prostate cancer incidence and mortality rates in South Australia. Med J Aust 1995; 162: 520-522. American College of Physicians. Screening for prostate cancer. Clinical Guideline: Part III. Ann Intern Med 1997; 126: 480-484. Hirst GH, Ward JE, Del Mar C. Screening for prostate cancer: the case against. Med J Aust 1996; 164: 285-288. Hahn DL, Roberts RG. PSA screening for asymptomatic prostate cancer: truth in advertising. J Fam Pract 1993; 37: 432-436. Woolf SH. Should we screen for prostate cancer? Men over 50 have a right to decide for themselves [editorial]. BMJ 1997; 314: 989-990. Flood AB, Wennberg JE, Nease RF Jr, et al. The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team. J Gen Intern Med 1996; 11: 2342-2349. Wolf AM, Nasser JF, Wolf AM, Schorling JB. The impact of informed consent on patient interest in prostate-specific antigen screening. Arch Intern Med 1996; 156: 1333-1336. Weller D, Pinnock C, Silagy C, et al. Prostate cancer testing in South Australian men: influence of sociodemographic factors, health beliefs and lower urinary tract symptoms. Aust N Z J Public Health 1998; 22: 400-402. Pinnock C, Marshall V. Troublesome lower urinary tract symptoms in the community: a prevalence study. Med J Aust 1997; 167: 72-75. Wilson D, Wakefield M, Taylor A. The South Australian Health Omnibus Survey. Health Prom J Aust 1992; 2: 47-49. Pinnock C, O'Brien B, Marshall V. Older men's concerns about their urological health: a qualitative study. Aust N Z J Public Health 1998; 22: 368-373. Kish L. Estimates of unit variance: design effect. In: Survey sampling. New York: John Wiley and Sons, 1965; 257-263. SPSS for Windows [computer program]. Version 7.5. Chicago, Ill: SPSS Inc, 1996. Robinson SB, Ashley M, Haynes MA. Attitudes of African Americans regarding screening for prostate cancer. J Natl Med Assoc 1996; 88: 241-246. Diefenbach PN, Ganz PA, Pawlow AJ, Guthrie D. Screening by the prostate-specific antigen test: what do the patients know? J Cancer Educ 1996; 11: 39-44. National Health and Medical Research Council. Clinical practice guidelines. The management of uncomplicated lower urinary tract symptoms in men. Canberra: Commonwealth of Australia, 1997. (Received 7 Nov 1997, accepted 7 May 1998) Authors' details Division of Surgery, Repatriation General Hospital, Daw Park, SA. Carole B Pinnock, PhD, Principal Research Scientist. Flinders University of South Australia, SA. David P Weller, FRACGP, FAFPHM, Senior Lecturer, Department of Evidence Based Care and General Practice; Villis R Marshall, MD, FRACS, Professor of Surgery, Department of Surgery, Flinders Medical Centre, and Head, Division of Surgery, Repatriation General Hospital, Daw Park, SA. Reprints will not be available from the authors. Correspondence: Dr C R Pinnock, Division of Surgery, Repatriation General Hospital, Daws Rd, Daw Park, SA 5041. E-mail: spinncbATrgh.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Carole B Pinnock · David P Weller · Villis R Marshall