Cancer

Healthcare Distribution of colorectal adenomas: implications for bowel cancer screening Fiona B Nicholson, Melvyn G Korman, Anthony I Stern and Jack Hansky MJA 2000; 172: 428-430 For editorial comment, see Mendelson & Forbes Abstract - Methods - Results - Discussion - References - Authors' details - - More articles on Oncology Abstract Objective: To determine the distribution of colorectal adenomas relative to the splenic flexure in an asymptomatic population undergoing colonoscopy, as an indicator of the number of patients with adenomas who would be missed by screening with flexible sigmoidoscopy. Design: Retrospective survey of medical records. Setting: Private endoscopy centres in Melbourne, Victoria. Subjects: All 1131 asymptomatic individuals who underwent full colonoscopy between 1 January 1995 and 31 December 1997 after referral from a bowel cancer prevention program organised by the endoscopy centres. People referred were aged either 40 years or over with a first-degree relative with bowel cancer, or 50 years or over with marked anxiety about bowel cancer. Main outcome measures: Presence and distribution of colorectal adenomas. Results: Polyps were found in 270 individuals (24%) and were confirmed to be adenomas in 138 (12%). These 138 comprised 106 men and 32 women, with mean age 54 years (range, 40-78 years). Most (86%) had a single adenoma. Position of adenomas in relation to the splenic flexure was: distal only in 85 of the 138 people (62%), proximal only in 34 (25%), and both distal and proximal in 19 (14%). Conclusions: In 25% of asymptomatic people found to have adenomas by this bowel cancer prevention program, the adenomas were found only in the proximal colon, well beyond the reach of the flexible sigmoidoscope. This distribution of adenomas suggests that screening programs cannot rely solely on flexible sigmoidoscopy. Colorectal cancer is the most common internal malignancy in Australia and the second most common cancer overall.1 One in 18 men and one in 27 women will develop this cancer during their lifetime.2 As most colorectal cancers are diagnosed at an advanced stage after symptoms develop, significant improvements in colorectal cancer mortality depend on prevention and early diagnosis. Most colorectal cancers develop from adenomatous polyps.3 If adenomas can be identified and removed, the adenoma-carcinoma sequence is broken, and colorectal cancer may be prevented.4 As adenomas usually cause few, if any, symptoms, they can be detected only by searching for them in asymptomatic individuals. While colonoscopic surveillance programs for detecting adenomas are accepted for those at higher risk of developing colorectal cancer (eg, with a family history),5 screening for the average-risk population remains controversial. In Australia, there are no population-based colorectal cancer screening programs, but the recent report from the Australian Health Technology Advisory Committee suggested pilot programs of faecal occult blood testing (FOBT) alone or in combination with flexible sigmoidoscopy.6 This combination is probably the most accepted method of screening for average-risk colorectal cancer. However, as adenomas and cancers may occur on the right side of the colon, and as not all of these bleed, they could be missed by this combination of tests. In 1991, some private endoscopy centres in Melbourne, Victoria, developed a Bowel Cancer Prevention Program. We aimed to determine how many asymptomatic people who underwent colonosocopy as part of this program had adenomas in the proximal colon only. This would indicate the number of patients with adenomas who would be missed by flexible sigmoidoscopy screening in an Australian population. Methods The study was a retrospective review of patient medical records. Data collection was approved by the Victorian Southern Health Care Network Ethics Committee. Subjects We examined the records of all asymptomatic individuals who underwent full colonoscopy between 1 January 1995 and 31 December 1997 after referral from the Bowel Cancer Prevention Program. Individuals with any symptoms that could be referable to colorectal cancer, such as rectal bleeding, anaemia, change in bowel habit or weight loss, were excluded from the study. The Bowel Cancer Prevention Program targets interested employees of major employer groups or members of participating unions and organisations. Each participant receives educational material about colorectal cancer and is asked to return a simple questionnaire. This assists an expert panel to assess and advise on individual risk of developing colorectal cancer, based on Gut Foundation7 and international guidelines.8 Asymptomatic individuals are referred for colonoscopy if: They are aged 40 years or over and have a self-reported family history of at least one first-degree relative with bowel cancer; or They are aged 50 years or over, and a doctor has requested a colonoscopy for bowel cancer screening because of the patient's marked anxiety. Procedures Informed consent was obtained, and a full colonoscopy was performed with visualisation of the caecum. Adenomas were confirmed by histological examination by private pathology services. Locations of adenomas were noted on the procedure report by the endoscopist at the time of colonoscopy. The position of the splenic flexure, as recognised at colonoscopy, was used to classify adenoma locations as: distal to the splenic flexure only; both distal and proximal to the splenic flexure; and proximal to the splenic flexure only. Data recorded The number of individuals with adenomas and the site of each adenoma within the colon and rectum were recorded, as were complications of sedation or the procedure. Results The records of 1131 asymptomatic individuals who underwent full colonoscopy were examined. The 1131 comprised 715 men and 416 women, with mean age 54 years (range, 40-78 years); 907 (80%) had a family history of colorectal cancer. None of the patients died or required hospitalisation for complications of sedation or the procedure. Colorectal polyps were found in 270 people (24%) and were confirmed to be adenomas in 138 (12%). These 138 comprised 106 men and 32 women, with mean age 54 years (range, 40-78 years). Adenomas were found in 118 of the 907 people with a first-degree relative with bowel cancer (13%) and in 20 of the 224 people whose only risk factor was age 50 years or more (9%). This difference in adenoma rates was statistically significant (P < 0.05). Most of the 138 patients (86%) had a single adenoma, while 14% had two or more. The adenomas ranged from 5 mm to 2 cm in diameter. Distribution of adenomas relative to the splenic flexure is shown in the Box. The distribution did not differ significantly between people who had a family history of colorectal cancer and those who did not: in both groups, 25% had adenomas proximal to the splenic flexure only. Discussion Different regimens are proposed for screening programs to prevent colorectal cancer. These include FOBT, periodic flexible sigmoidoscopy, FOBT combined with flexible sigmoidoscopy, or full colonoscopy. The rationale for a screening sigmoidoscopy is that it would detect most adenomas, as they are most common in the left colon. Further, in those with adenomas (or cancer) proximal to the splenic flexure, the theory is that adenomas would also be found in the distal colon by flexible sigmoidoscopy, thus signalling the need for full colonoscopy -- the concept of the "sentinel" polyp [adenoma].8This theory is not supported by the results of our study. We found that in 25% of asymptomatic individuals with adenomas, the adenomas were found only in the proximal colon, beyond the reach of the flexible sigmoidoscope. This figure is consistent with other studies.9 A sentinel adenoma on the left side signalling proximal adenomas was found in only 14% of people; 62% of subjects had only left-sided adenomas. In our study the distribution of adenomas was assessed from the endoscopists' reports. Experienced endoscopists are correct in determining scope-tip position 83% of the time.10 One cannot assume that a 60 cm flexible sigmoidoscope will reach the splenic flexure. Indeed, a recent report suggests that it reaches 60 cm in only 34% of cases, and far less often in women than in men, with the problem worsening with increasing patient age.11 There are no other Australian data on the incidence or distribution of adenomatous polyps in the colon and rectum. Collett et al showed that distal colorectal cancer or adenomas predicted proximal neoplasia in 30% of subjects, but their study was based on colonoscopy only after a positive result from flexible sigmoidoscopy.12 Their study design did not allow them to accurately determine the distribution of adenomas in the colon and rectum. Colonoscopy remains the final diagnostic pathway for any positive result for a bowel cancer screening test. Some international experts recommend use of colonoscopy as the optimum screening tool to prevent the development of colorectal cancer.13 However, it has not been embraced as the primary screening modality because of concerns about cost, compliance and risk. The risks of colonoscopy include those related to sedation, as well as the procedure, such as perforation (reported at 1 in 200014) and bleeding complicating polypectomy. Complication rates are usually derived from hospital populations, which include many ill patients who have significant comorbidity, and it may be that the risk is considerably less in the far healthier "screening" population. No significant sedation- or procedure-related complications or deaths occurred in our comparatively small series of colonoscopies. The proportion of men to women in the group with the adenomas was about 2:1. This probably reflects our target population rather than a true difference in the incidence of adenomas. However, men are significantly more likely to develop colorectal cancer than women.15 Unfortunately, most reported case series of adenomas have studied populations heavily biased with men. Larger studies examining the influence of sex on adenoma frequency and distribution within the colon and rectum are needed. Well-designed overseas studies have confirmed that programs based on annual FOBT followed by colonoscopy for those with positive FOBT results significantly reduce anticipated mortality from colorectal cancer.16,17 Adding flexible sigmoidoscopy to FOBT to detect proximal adenomas seems sensible but adds significantly to cost. Indeed, a recent Australian economic study using computer modelling clearly showed that only FOBT or five- or 10-yearly colonoscopy are cost-effective bowel-cancer screening methods; flexible sigmoidoscopy alone or in combination with FOBT was not cost-effective.18 The distribution of adenomas found in our study adds weight to the recent suggestion that it is time to consider adding full colonoscopy to the menu of options available to general practitioners when discussing bowel cancer screening and prevention with their patients.19 References Coates M, Day P, McCredie M. Cancer in New South Wales: incidence and mortality 1992. Sydney: NSW Cancer Council, 1995. Australian Institute of Health and Welfare and the Australasian Association of Cancer Registries. Cancer in Australia 1991-1994 (with projections to 1999). Canberra: AIHW, 1998. Muto T, Bussey H, Morson B. The evolution of cancer in the colon and rectum. Cancer 1975; 36: 2251-2270. Winawer S. The National Polyp Study. Design, methods, and characteristics of patients with newly diagnosed polyps. The National Polyp Study Workgroup. Cancer 1992; 70: 1236-1245. National Health and Medical Research Council. Clinical practice guidelines. The prevention, early detection and management of colorectal cancer. Canberra: NHMRC, 1999. Australian Health Technology Advisory Committee. Colorectal cancer screening. Canberra: AGPS, 1997. Gut Foundation of Australia. Colorectal cancer prevention, diagnosis and treatment (public information booklet). Sydney: The Foundation, 1999. Winawer S, Fletcher R, Miller L, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; 112: 594-642. Kadakia S, Wrobleski C, Kadakia A. Prevalence of proximal colonic polyps in average-risk asymptomatic patients with negative fecal occult blood tests and flexible sigmoidoscopy. Gastrointest Endosc 1996; 44: 112-117. Shah S, Saunders B, Brooker J, Williams C. What happens during routine colonoscopy? An audit using magnetic positional imaging (MPI). Gut 1999; 44 Suppl 1: A105. Jacobs J, Burke C, Larive B. 60 cm flexible sigmoidoscopy, how far do we really get? [abstract] Gastroenterology 1999; 116 (4 Pt 2): A428. Collett J, Platell C, Fletcher D, et al. Distal colonic neoplasms predict proximal neoplasia in average-risk, asymptomatic subjects. J Gastroenterol Hepatol 1999; 14: 67-71. Rex D, Amitabh C, Vasudeva R. Prospective determination of distal colon findings in average-risk patients with proximal colon cancer. Gastrointest Endosc 1999; 49: 727-730. Basson M, Etter L, Panzini L. Rates of colonoscopic perforation in current practice. Gastroenterology 1998; 114: 1115. Rex D, Lehman G, Ulbright T, et al. Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender and family history. Am J Gastroenterol 1993; 88: 825-831. Mandel J, Bond J, Church T. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993; 328: 1365-1371. Hardcastle J, Chamberlain J, Robinson M, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472-1477. Bolin T, Korman M, Stanton R. Positive cost effectiveness of early diagnosis of colorectal cancer. Colorectal Dis 1999; 1: 113-122. Bolin T, Korman M. How can we reduce the incidence and mortality of colorectal cancer? Med J Aust 1997; 166: 175-176. (Received 5 Nov 1999, accepted 24 Jan 2000) Authors' details Gastroenterology Unit and Department of Medicine, Monash Medical Centre, Melbourne, VIC. Fiona B Nicholson, FRACP, Fellow; Melvyn G Korman, PhD, FRACP, Director; Anthony I Stern, PhD, FRACP, Visiting Physician; Jack Hansky, FRACP, Visiting Physician. Reprints: Dr M G Korman, Department of Gastroenterology, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168. m.kormanATshcn.com.au Make a comment Back to text

Fiona B Nicholson · Melvyn G Korman · Anthony I Stern · Jack Hansky

Editorial Breast cancer guidelines in action The challenge is to develop and sustain audit programs on an ongoing basis MJA 2000; 172: 196-197 In 1995, when the National Health and Medical Research Council (NHMRC) released Clinical practice guidelines for the management of early breast cancer,1 the first of their evidence-based recommendations, the initial response by clinicians was very positive: 97% regarded them as a good summary of recent evidence and 85% believed they would be useful in improving management.2This was encouraging, but the more important question was whether the guidelines would result in evidence-based care for women with breast cancer. Until recently, there has been little national information about breast cancer management in Australia, a lack noted by the House of Representatives in 1995, whose response was to recommend a comprehensive national monitoring system.3 However, it was not until 1999 that an accurate national picture of breast cancer management emerged. A report by the NHMRC National Breast Cancer Centre,4 analysing the surgical management of 4237 women with breast cancer in 1995 (ie, 88% of all women in Australia diagnosed with breast cancer in the six months before release of the guidelines), showed that, at that time, most women were receiving care in accord with most of the recommendations. However, some aspects of care were not in line with the guidelines: for example, the report highlighted the need to encourage the use of tamoxifen in women with oestrogen receptor positive tumours (particularly in women less than 50 years); to decrease rates of testing for distant metastases at the time of diagnosis of early breast cancer; and to increase participation in clinical trials. Progress will occur only if other local groups also see value in promoting evidence as their mast-head and recognising the fundamental role of audit in evidence-based treatment Information about current practice plays a key role in supporting evidence-based care. It enables the best use of scarce resources, as costly implementation strategies can be targeted at aspects of care not in accord with the recommendations. The process of audit itself is also effective in changing practice, particularly if individual clinicians can compare their own practice with evidence-based recommendations or with the practice of their peers.5,6 In this context, the article in this issue of the Journal by Craft et al 7 is of considerable significance, as it demonstrates the feasibility of a community-based audit of breast cancer management by a multidisciplinary team (the Australian Capital Territory and South Eastern New South Wales [ACT and SE NSW] Breast Cancer Treatment Group). The Group is to be commended both for its meticulous approach to encouraging evidence-based care through local audit and for the high standards of care provided. The results presented by Craft et al7 suggest that more women than in the national survey were managed in accordance with the NHMRC guidelines. For example, in the national data, 85% of women with breast-conserving therapy received radiotherapy, compared with 98% of the sample studied by Craft et al, and all women in the sample aged under 50 with axillary node involvement received adjuvant chemotherapy. We do not know, of course, to what extent these results can be generalised to the 21% of cases occurring in the region and not included in the audit. Although these differences may show an embracing of the guidelines since their release, it is unclear whether these changes would be apparent across Australia or whether they are due to intensive efforts within the ACT and SE NSW region. However, an audit conducted in a surgical practice in Echuca, a rural town in Victoria, also demonstrated patterns of care generally in accordance with the guidelines.8 The report by Craft et al also shows the role of local ownership of guidelines and a multidisciplinary team approach to management. The ACT and SE NSW Breast Cancer Treatment Group was formed to consider priorities within the region and to select indicators of local significance for inclusion in their audit. Consumer input was included. Further, the audit was not limited to one institution, but attempted to include all clinicians, including potentially more isolated clinicians in the region, making it more likely to have an impact on outcomes. The strategies used by the Group appear to have been successful, with 23 of 24 clinicians participating and the identification of an estimated 79% of all cases of breast cancer occurring in the region. There is some evidence that a multidisciplinary team approach is more likely to result in evidence-based care and better patient outcomes than clinicians working in isolation.9,10 Recent initiatives within Australia are designed to foster multidisciplinary care, including Victoria's Breast Care Enhancement Program and the federally funded National Multidisciplinary Care Demonstration Project coordinated by the National Breast Cancer Centre. After Craft et al's conclusive demonstration of the value of local audit, the challenge now is to develop and sustain other audit programs on a continuing basis. There is a real danger that the evidence-based approach will founder from a lack of resources for guideline implementation at the local level and for support of audit programs. A commitment from State and local health services to resourcing these programs is vital. The recent initiative by the Royal Australasian College of Surgeons in developing an audit system for breast cancer should prove particularly valuable in future assessment of guideline adherence. The audit is national and provides contributing surgeons with feedback about their practice compared with that of their peers. There are also benefits to daily clinical practice: the audit provides a standardised record, which can be used in patient notes or to inform general practitioners or patients. Apart from surgery, other disciplines are also considering developing similar approaches to audit in breast cancer, notably the Royal Australian and New Zealand College of Radiologists (Faculty of Radiation Oncology) and the Medical Oncology Group, all in association with the National Breast Cancer Centre. Progress will occur only if other local groups also see value in promoting evidence as their masthead and recognising the fundamental role of audit in evidence-based treatment. In demonstrating the feasibility of this approach, the achievement of the ACT and SE NSW Breast Cancer Treatment Group could serve as a model for other regions. Sally Redman Director, NHMRC National Breast Cancer Centre, Sydney, NSW Tom S Reeve Executive Officer, Australian Cancer Network, Sydney, NSW National Health and Medical Research Council. The management of early breast cancer. Clinical Practice Guidelines. Canberra: NHMRC/AGPS, 1995. Carrick S, Bonevski B, Redman S, et al. Surgeons' opinion about the NHMRC clinical practice guidelines for the management of early breast cancer. Med J Aust 1998; 169: 300-305. House of Representatives Standing Committee on Community Affairs. Report on the management and treatment of breast cancer in Australia. Canberra: AGPS, 1995. Hill D, Jamrozik K, White V, et al. Surgical management of breast cancer in Australia in 1995. Sydney: NHMRC National Breast Cancer Centre; 1999. Thomson MA, Oxman AD, Davis DA, et al. Audit and feedback to improve health professional practice and health care outcomes (Parts I and II) (Cochrane Review). Oxford: The Cochrane Library 1999: Issue 1. NHS Centre for Reviews and Dissemination, University of York. Getting evidence into practice. Effective Health Care 1999; 5(1). Craft PS, Zhang Y, Brogan J, et al, and the Australian Capital Territory and South Eastern New South Wales Breast Cancer Treatment Group. Implementing clinical practice guidelines: a community-based audit of breast cancer treatment. Med J Aust 1999; 172: 213-216. Tulloh BR, Goldworthy ME. Breast cancer management: a rural perspective. Med J Aust 1997; 166: 26-29. Sainsbury R, Haward B, Rider L, et al. Influence of clinician workload and patterns of treatment on survival from breast cancer. Lancet 1995; 345: 1251-1252. Gillis CR, Hole DJ. Survival outcome of care by specialist surgeons in breast cancer: a study of 3786 patients in the west of Scotland. BMJ 1996; 312: 145-148. Make a comment

Healthcare Implementing clinical practice guidelines: a community-based audit of breast cancer treatment Paul S Craft, Yanping Zhang, Jennifer Brogan, Noel Tait, John M Buckingham, and the Australian Capital Territory and South Eastern New South Wales Breast Cancer Treatment Group MJA 2000; 172: 213-216 For editorial comment, see Redman & Reeve Abstract - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - More articles on Oncology Abstract Objective: To improve breast cancer management by facilitating implementation of treatment guidelines. Design: A prospective, longitudinal study (developed by clinicians and consumers) of all patients with newly diagnosed breast cancer. Four locally agreed breast cancer management guidelines were established (based on 1995 National Health and Medical Research Council guidelines) as practice indicators. Setting: Breast cancer treatment facilities and medical practices in the Australian Capital Territory and South Eastern New South Wales, May 1997 to July 1998. Main outcome measures: Actual treatment received by patients for primary breast cancer during the study period. Results: During the 14 months of the study, 19 clinicians registered 221 new patients with a proven diagnosis of breast cancer. Of 191 women with localised invasive breast cancer, 112 (59%) had tumours 2 cm or less in diameter. Axillary surgery in 173 (91%) of these women showed 107 (56%) had no axillary lymph node involvement. Of 87 women treated with breast-conserving surgery for locally invasive cancer, 85 (98%) also received postoperative radiotherapy. Some form of systemic adjuvant therapy was indicated in 99 women (axillary nodes positive or tumours > 2 cm diameter) and this treatment was received by 95 (96%). All 27 women aged under 50 years with node-positive disease received adjuvant chemotherapy. Conclusions: Enhancing uptake of breast cancer management guidelines is feasible at a regional level with an audit program and broad support among clinicians and consumers. Breast cancer is a major health problem in Australia, with 9800 new cases diagnosed each year.1 Management guidelines for early breast cancer were developed in 1995 by the National Health and Medical Research Council (NHMRC) to assist clinicians and consumers make decisions about treatment and thus to improve health outcomes.2 Observed differences in treatment outcome between populations suggest that opportunities for improvement are available.3 Moreover, potentially important variations in clinical practice are well documented in Australia and elsewhere.4-6 Treatment practice which appears to be informed by evidence, for example greater use of breast-conserving surgery, has been observed more frequently among clinicians who regularly treat patients with breast cancer.7 Furthermore, congruence of treatment practice with published guidelines has been directly associated with improved patient survival;8 improved treatment practice has the potential to improve survival by up to 10%.8,9 Therefore, enhanced implementation of soundly developed, evidence-based treatment guidelines is an appropriate goal for health services and individual clinicians. In 1996, clinicians and consumers involved in breast cancer diagnosis and treatment in the Australian Capital Territory (ACT) and South Eastern New South Wales (SE NSW) formed a cooperative group aimed at improving breast cancer management and facilitating implementation of treatment guidelines. A prospective, longitudinal, community-based study of breast cancer treatment was established to assist with guidelines implementation. Our report describes the results of the first 14 months of this ongoing project. Methods Breast Cancer Treatment Group All surgeons, radiation oncologists, medical oncologists, radiologists, pathologists, nurses and other health professionals who were known by the ACT Breast Screen Program to be involved in the treatment of breast cancer in the ACT and SE NSW were invited by mail to participate in a multidisciplinary breast cancer treatment group. Consumer representatives from "The Bosom Buddies", a community organisation of women with a history of breast cancer, were also invited to join the group. Fifty consumers and clinicians expressed interest and continue to receive all correspondence, with meetings every two months attracting between 15 and 30 attendees. A general practitioner representative from the ACT Division of General Practice also participated. The Breast Cancer Treatment Group adopted treatment guidelines based on the NHMRC Clinical Practice Guidelines, commenced a community-based audit, and later developed a set of agreed practice indicators against which treatment decisions could be compared. The 1998 estimated populations of the ACT and South Eastern NSW were 311 000 and 118 000 respectively (source: Australian Bureau of Statistics, Estimated Residential Populations, 30 June 1998). Practice indicators The group adopted four indicators for which unanimous local agreement about the relevant guideline was available: Women with operable invasive breast cancer should undergo some form of axillary surgery sufficient to develop a prognosis based on axillary node status; Women undergoing less than total mastectomy for operable invasive breast cancer should receive postoperative adjuvant radiotherapy; Women with a completely resected invasive breast cancer tumour greater than two centimetres in diameter or with involved axillary lymph nodes should receive adjuvant systemic therapy (either chemotherapy, endocrine therapy or both); and Women under the age of 50 years with completely resected axillary lymph node positive breast cancer should receive adjuvant chemotherapy. Audit A prospective study of breast cancer treatment was commenced in May 1997. The study was designed as a quality assurance project and notified as such under Section 7 of the Health Act 1993 (ACT) in June 1997. The study was approved by the Ethics Committee of the ACT Department of Health and Community Care. All clinicians involved specifically with the care of patients with breast cancer were invited to participate in the study. Participating clinicians agreed to approach all of their patients presenting with newly diagnosed breast cancer requesting permission to include them in the study. Eligible patients were women or men with newly diagnosed invasive or in-situ breast cancer. For each eligible patient a brief notification form was completed and submitted by mail to the study centre at the Women's Health Program of ACT Community Care. Written informed consent was obtained from the patient by the notifying clinician, and subsequently a detailed data form was completed giving details of presentation, clinical and pathological staging, and treatment. The dataset was based on a prior survey conducted by the Provincial Surgeons of Australia (Dr David Adamthwaite, President of the Provincial Surgeons of Australia, personal communication). Additional data relating to enrolled patients were obtained from treatment units in the region. Information from the audit forms, supplemented where necessary from pathology reports and treatment facility records, was entered into a secure database developed by the project officer. As well as facilitating project management, the database allows individualised, confidential reports to be produced for each participating clinician, providing detailed feedback about each clinician's practice, with comparisons across the group and against the agreed criteria. Aggregated data across the whole clinician group are presented at regular meetings of the treatment group. Data collected during the first 14 months of the project, and analysed to provide an initial report to contributing clinicians, form the basis of our report. Accrual of patients to the project is ongoing. Results Specialist participation Since commencement of the project, 23 of 24 medical specialists known to treat breast cancer within the region have registered as participants, with 19 specialists contributing data to the study to date (13 surgeons, three radiation oncologists and three medical oncologists). All of the radiation and medical oncologists were based in Canberra, while the principal practices of six surgeons were based in SE NSW. Patient accrual During 14 months from May 1997 to July 1998, 221 patients, including four men, with a diagnosis of primary breast cancer were registered for the study (Box 1). Some 123 new cases of invasive breast cancer (excluding male patients and patients with in-situ disease only) were registered with ACT addresses. In comparison, the observed mean annual incidence of breast cancer in the ACT during 1993-1996 was 134.1 Thus, during the 14-month study period, about 156 incident cases would be expected. The project therefore detected 79% of predicted ACT incident cases during the study period. Of the 221 registered patients, there were 10 with distant metastases, 16 with carcinoma-in-situ only and four men, leaving 191 women with primary, localised, invasive breast cancer. It is to these women that the treatment guidelines apply. In five women with bilateral synchronous tumours, details are given of the tumour judged by the treating clinician to have the worse prognosis. Eighty-one per cent of tumours were oestrogen receptor (ER) positive or progesterone receptor (PgR) positive by immunohistochemical analysis done in routine diagnostic histopathology laboratories. The pathological characteristics of the tumours in these 191 women are presented in Box 2. Comparisons with practice indicators (Box 3) Axillary surgery was undertaken in 173 women. One elderly patient declined to have any surgery. Thus, 17 of 190 patients did not undergo any form of axillary surgery, at variance with the guideline. Of these women, six were aged 80 years or older. Seven of the remaining 11 patients had tumours less than 1 cm in diameter. Among women having axillary surgery, five (3%) had four or fewer nodes resected. Only two of 87 women who underwent breast-conserving surgery did not also receive postoperative radiotherapy. Of the 191 patients with invasive breast cancer, 103 (54%; 95% CI, 47-61) underwent mastectomy. The overall concordance of treatment with the practice indicators relating to systemic adjuvant therapy was strong. Of 33 women with tumours greater than 2 cm in diameter and negative or unknown axillary lymph node status, 32 (97%) received either tamoxifen (18), chemotherapy (4), or both (10). Of 66 women with axillary lymph node involvement, 63 (95%) received systemic adjuvant therapy with either tamoxifen (14), chemotherapy (19) or both (30). Thus, only four of 99 women for whom adjuvant systemic therapy was considered appropriate under the guidelines did not receive such therapy. All 27 women under 50 years of age with axillary lymph node involvement received adjuvant chemotherapy. Data quality The project officer actively sought clarification of ambiguous or missing data items. Initial notification forms required clarification for 192 of 221 registrations. Of these queries, one follow-up data request was required for 91 patients, two requests for 60 patients and three requests for 41 patients. After these data requests, 3.6% of records remained incomplete in some way. Initial under-reporting of adjuvant treatments received was noted, particularly in regard to postoperative radiotherapy. Discussion Our report demonstrates the feasibility of regionally based multidisciplinary groups adopting treatment guidelines and then assessing their implementation. Strong concordance of practice with the four practice indicators was observed. Despite a third of our patients living in rural areas, there were high rates of postoperative radiotherapy after breast-conserving surgery. The rate of axillary surgery was lower than recommended, but in almost all of these women a partial explanation was available (advanced age or very small primary tumour). Whether the decision not to perform axillary surgery in these patients was appropriate is the subject of debate and ongoing clinical trials. Given the degree of involvement of clinicians in establishing the data collection and practice indicators, the strong concordance with actual practice observed is not surprising. The practice indicators chosen were not particularly controversial, enabling rapid consensus among the group members. Indicators relating to the use of breast-conserving surgery for early breast cancer and to the use of adjuvant chemotherapy for node-negative disease, although more contentious, are appropriate further areas for local consensus and audit. Observed concordance with guidelines for adjuvant chemotherapy in node-negative breast cancer has been relatively low, presumably because of the more modest benefits of treatment (in absolute terms) in this group.11 Implementing guidelines successfully can be difficult. Just producing and publishing guidelines for breast cancer treatment does not ensure their uptake into clinical practice.12 Over time clinical practice may adhere more closely to published guidelines, although a causal relationship cannot be easily proven.13 In a survey of clinicians in Sydney, most respondents supported the NHMRC Clinical Practice Guidelines, but only 20% believed the guidelines had influenced clinical practice.14 The introduction of guidelines has been a stimulus for institutionally focused audits of surgical practice.15 Audits incorporating structured feedback to clinicians may be a critical strategy in implementing guidelines. Organisations such as the Royal Australasian College of Surgeons have recognised audit as an important tool in the treatment of breast cancer, and Clinical Indicator 7.1 of the Australian Council of Healthcare Standards Internal Medicine Indicators, version 2, measures the proportion of premenopausal women with node-positive early breast cancer receiving chemotherapy.16 Many factors affect treatment decisions in primary breast cancer. Women bring to the process their own preferences and needs. Many of the treatment decisions require trade-offs between long term gain and unpleasant treatments, such as chemotherapy. We did not examine the decision-making processes followed by these patients and their attending health professionals. Entry of any individual patient into the audit was voluntary, both for the clinician and for the patient. Participating clinicians undertook to offer enrolment to all of their patients, and every effort was made to enhance compliance. Nevertheless, complete enrolment was not achieved and this may have introduced bias, with patients receiving multimodality care possibly being more likely to be enrolled. An advantage of our audit was that it was community based and prospective. Surgical audits have generally been based on retrospective casenote review and, as such, have sometimes been hampered by missing data.17 Some community-based studies assessing the process of treatment have relied on the secondary analysis of administrative data with linkage to population-based cancer registries.18 In Canada, a population-based cancer registry has been linked to clinical records to obtain treatment details and allow comparisons with treatment guidelines.19 Successful collection of community-based audit data requires both enthusiasm and trust on the part of the treating clinicians voluntarily submitting information about their own practice. We believe this may be best achieved within a framework of agreed treatment guidelines and indicators. An enthusiastic project officer and involvement of practice staff and institutional data managers is crucial. As new ways of managing breast cancer (and other diseases) become available, an ongoing implementation process with agreed, clinically relevant indicators and guidelines, and a regionally based audit, can be an effective tool. Members of the Australian Capital Territory and South Eastern New South Wales Breast Cancer Treatment Group contributing to the study Chairperson Dr Doris Zonta. Surgeons Bega, NSW: Dr Andrew Thomson. Canberra, ACT: Dr Guan Chong, Dr Ian Davis, Dr Dennis Dyason, Dr Diarmid McKeown, Dr John Stuchbery Goulburn, NSW: Dr Margaret Beevors, Dr John Hayman. Moruya, NSW: Dr Peter Gough, Dr John Groome, Dr David Thomson. Medical Oncologists Canberra, ACT: Associate Professor Robin Stuart-Harris, Dr William Coupland. Radiation Oncologists Canberra, ACT: Dr Deborah Thornton, Dr George Jacob, Dr Kenneth Sunderland. Epidemiologist Canberra, ACT: Dr Bruce Shadbolt. Pathologists Canberra, ACT: Dr Jane Dahlstrom, Dr Sanjiv Jain. Acknowledgement Initial funding was provided by the Commonwealth Department of Health and Aged Care Cancer Screening Unit. References Australian Institute of Health and Welfare. Breast and cervical cancer screening in Australia 1996-1997. Canberra: AIHW, 1998: 33. (Cancer Series no. 8.) National Health and Medical Research Council. Clinical practice guidelines. The management of early breast cancer. Canberra: NHMRC, 1995. Richards M, Sainsbury R, Kerr D. Inequalities in breast cancer care and outcome. Br J Cancer 1997; 76: 634-638. Craft PS, Primrose JG, Lindner JA, McManus PR. Surgical management of breast cancer in Australian women in 1993: analysis of Medicare statistics. Med J Aust 1997; 166: 626-629. Nattinger AB, Goottlieb MS, Veum J, et al. Geographic variation in the use of breast-conserving treatment for breast cancer. N Engl J Med 1992; 326: 1102-1107. Samet JM, Hunt WC, Farrow DC. Determinants of receiving breast-conserving surgery. The surveillance, epidemiology and end results program 1983-1986. Cancer 1994; 73: 2344-2351. Hill DJ, White VM, Giles GG, et al. Changes in the investigation and management of primary operable breast cancer in Victoria. Med J Aust 1994; 161: 110-122. Sainsbury R, Haward B, Rider L, et al. Influence of clinician workload and patterns of treatment on survival from breast cancer. Lancet 1995; 345: 1265-1270. Gillis CR, Dole D. Survival outcome of care by specialist surgeons in breast cancer: a study of 3786 patients in the west of Scotland. BMJ 1996; 312: 145-148. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19: 403-410. Sawaka C, Olivotto I, Coldman A, et al. The association between population-based treatment guidelines and adjuvant therapy for node-negative breast cancer. Br J Cancer 1997; 75: 1534-1542. Chouillet AM, Bell CM, Hiscox JG. Management of breast cancer in southeast England. BMJ 1994; 308: 168-171. Ray-Coquard I, Philip T, Lehmann M, et al. Impact of a clinical guidelines program for breast and colon cancer in a French cancer center. JAMA 1997; 278: 1591-1595. Ward JE, Boyages J, Gupta L. Local impact of the NHMRC early breast cancer guidelines: where to from here? Med J Aust 1997; 167: 362-365. McCarthy DO, Blamey RW, Robertson JF, Mitchell AK. A one-year audit of 255 operable breast cancers. Eur J Surg Oncol 1997; 23: 399-402. Australian Council on Healthcare Standards. Clinical indicators in summary. Revised edition. Sydney: ACHS, 1998. Clamp SE. Management of breast cancer. Incomplete case notes hamper research. BMJ 1994; 308: 715. Hillner BE, McDonald MK, Penberthy L, et al. Measuring standards of care for early breast cancer in an insured population. J Clin Oncol 1997; 15: 1401-1408. Olivotto IA, Coldman AJ, Hislop TG, et al. Compliance with practice guidelines for node-negative breast cancer. J Clin Oncol 1997; 15: 216-222. (Received 29 Jul, accepted 4 Dec, 1999) Authors' details Medical Oncology Unit, The Canberra Hospital, Canberra, ACT. Paul S Craft, MPH, FRACP, Director. Women's Health Program, ACT Community Care, Canberra, ACT. Yanping Zhang, Project Officer; Jennifer Brogan, Director. The Calvary Clinic, Canberra, ACT. Noel Tait, FRACS, Consultant Surgeon; John M Buckingham, FRACS, Consultant Surgeon. Reprints: Dr P S Craft, Medical Oncology Unit, The Canberra Hospital, PO Box 11, Woden, ACT 2606. Paul_CraftATact.gov.au Make a comment 1: Patient and tumour characteristics for all registered breast cancer patients (n=221)nPercentage (95% CI)Median age, 57 years (range, 25-88)SexMale42% (1%-5%)Menopausal statusPremenopausal63 29% (23%-35%)Postmenopausal12557% (50%-63%)Perimenopausal2712% (8%-17%)Unknown or male63% (1%-6%)Place of residenceAustralian Capital Territory14767% (61%-73%)DiagnosisIn-situ disease only167% (4%-11%)Invasive carcinoma20593% (89%-96%)Tumour extentDistant metastases at diagnosis105% (3%-9%)Synchronous bilateral tumours52% (1%-5%) Back to text 2: Pathological characteristics of the tumour in 191 women with invasive breast cancer and no distant metastases CharacteristicnPercentage (95% CI)Tumour size (mm)0-103016% (11%-22%)11-208243% (36%-50%)21-506233% (27%-40%)>50147% (4%-12%)Unknown32% (1%-5%) Axillary lymph node statusNegative107 56% (49%-63%)Positive66 35% (29%-42%)No axillary surgery168% (5%-13%)Unknown21% (1%-5%) CharacteristicnPercentage (95% CI)Tumour type and grade*Invasive ductalGrade 12915% (11%-21%)Grade 26635% (29%-42%)Grade 35328% (22%-35%)Invasive lobular2010% (7%-15%)Special types†2312% (8%-17%)Receptor statusER positive or PgR positive15581% (75%-86%)ER negative and PgR negative3016% (11%-22%)Unknown63% (1%-6%) *See Elston and Ellis.10 †Includes seven tubular, four mucinous, six cribriform, one papillary, one medullary, one squamous cell, and one metaplastic carcinoma. There was also one spindle cell tumour and one cystosarcoma phylloides tumour reported. ER=Oestrogen receptor. PgR=Progesterone receptor. Back to text 3: Women with breast cancer - comparison of treatment received with practice indicators Indicatorn Percentage (95% CI)Breast-conserving surgeryRadiotherapy8598% (92%-99%)No radiotherapy22% (1%-8%)Total87 100%Surgery for invasive cancerAxillary surgery17391% (86%-94%)No axillary surgery179% (6%-14%)Total190 100%Axillary nodes positive or tumours >2 cmSome form of adjuvant systemic therapy95 96% (90%-98%)No adjuvant systemic therapy44% (2%-10%)Total99100%Women aged less than 50 years with positive axillary nodesAdjuvant chemotherapy27100%No adjuvant chemotherapy00Back to text

Paul S Craft · Yanping Zhang · Jennifer Brogan · Noel Tait · John M Buckingham

Abstract Objective: To assess Australian radiation and medical oncologists' self-reported knowledge about and attitudes towards a range of non-traditional therapies used by people with cancer. Design: Postal survey during May and June 1997 of all 265 radiation and medical oncologists practising in Australia. Participants: 161 oncologists returned surveys (61% response rate). Main outcome measures: Oncologists' own level of knowledge, and, for each known therapy, their perceptions of its likely harm or benefit in patients being treated curatively and palliatively, and of the prevalence of use among their patients. Results: Oncologists reported knowing most about acupuncture, antioxidant therapy and meditation and least about cellular therapy, magnetotherapy and psychic surgery. The therapies most likely to be considered helpful were meditation, acupuncture and hypnotherapy. Those most likely to be considered harmful were coffee enemas, psychic surgery, Iscador therapy and diet therapies. Perceptions of patients' use of most therapies varied widely, with herbal therapies, antioxidant therapy and meditation considered the most commonly used. Conclusions: These results indicate self-identified gaps in oncologists' knowledge about non-traditional therapies their patients may use; they suggest a need to consider including education about these therapies in oncologists' training. Introduction Recent studies have confirmed the popularity of non-traditional therapies among Australian cancer patients: 22%-52% of medical oncology patients,1,2 40% of those being treated palliatively3 and 46% of children with cancer4 report using at least one non-traditional therapy. Many of the most popular non-traditional therapies are psychosocial (eg, relaxation, meditation and visual imagery) and are unlikely to pose threats to patients' health.1-4 However, other popular therapies include dietary therapies, antioxidants, high dose vitamins and herbal therapies,1-4 many of which are poorly evaluated and could pose physical threats to patients, either directly, or by interfering with traditional therapies. Despite the lack of scientific evidence, 25%-73% of patients using non-traditional therapies expect them to cure their cancer or to prolong their lives,1-4 and 74%-86% expect them to assist their traditional therapies.2 Despite fairly high reported levels of satisfaction and perceived benefit with non-traditional therapies,1,2 17% of patients in one study reported negative side effects,4 10%-36% of patients reported no perceived benefit or feeling worse,1,2 and around 20% reported they would not take the therapy again or recommend it to other patients.2 Even if not harmful, many non-traditional therapies are expensive,1,2 and only 64% of patients felt the non-traditional therapies provided value for money.1 Recent guidelines highlight the need for oncologists to be aware of non-traditional therapies being used or considered by their patients, and to encourage patients to discuss them.5 This would require oncologists having at least a basic understanding of these therapies. We were able to identify only two relevant studies in this area -- a quantitative survey of 106 Italian oncologists6 and a qualitative study of 18 Canadian oncologists.7 They found limited knowledge about non-traditional therapies,6,7 relatively positive attitudes towards psychological therapies,6,7 more negative attitudes towards more invasive therapies,7 negative attitudes towards non-traditional therapy practitioners6 and more positive attitudes towards the use of non-traditional therapies by palliative patients.7 As there is a lack of data in this field, we explored Australian medical and radiation oncologists' knowledge of and attitudes to non-traditional therapies, and their perceptions of the frequency with which their patients used them. Given the increased tolerance among overseas oncologists of palliative patients using non-traditional therapies,7 we assessed attitudes to palliative and curative patients separately. We use the term "non-traditional therapies" to describe all therapies other than surgery, radiotherapy, chemotherapy and hormone therapy. Methods In May and June 1997, 273 questionnaires about 19 non-traditional therapies covering a wide range of psychosocial and physical therapies commonly discussed in the literature and media were mailed to all oncologists who practise in Australia. Non-responders received a written reminder after four weeks and a telephone reminder after six weeks. Ethical approval for this study was granted by the University of Newcastle's Human Research Ethics Committee. Sample identification We identified all medical and radiation oncologists practising in Australia through the Clinical Oncological Society of Australasia (COSA) and the Royal Australasian College of Radiologists' (RACR) Faculty of Radiation Oncology. The list of all the individuals registered with the Medical and Radiation Oncology Groups of COSA in late April 1997 comprised 155 Australian-based medical oncologists and 62 radiation oncologists. As the Medical Oncology Group of Australia advised they were aware of only 165 practising Australian-based medical oncologists, we considered the COSA list comprehensive for medical oncologists. However, the RACR advised they had 123 members currently practising in Australia, and, in line with its policy of not releasing members' contact details, they agreed to mail surveys to any of their members not on the COSA list -- an additional 56 radiation oncologists. The final sample of 273 thus comprised 155 medical and 118 radiation oncologists. The survey We designed a brief survey whereby oncologists rated, on a four-point scale ("none/never heard of it", "very little", "some" or "lots"), their own levels of knowledge about each of 19 non-traditional therapies; we provided no additional information about these therapies. Oncologists were also asked to rate each therapy they knew (also on a four-point scale: "very", "fairly", "neither" or "don't know"), according to how harmful or helpful they considered it for patients being treated palliatively and curatively. Finally, they were asked to estimate the proportion of their palliative and curative patients they believed were using, or had used, each known therapy. Copies of the survey may be obtained from the authors. Statistical analysis We report descriptive statistics on oncologists' knowledge and attitudes, including 95% confidence intervals around the proportion of oncologists knowing "lots" about each therapy. All analyses were conducted with the SAS statistical package;10 95% confidence intervals were calculated using Microsft Excel,11 based on the standard binomial approximation formula.12Results Of the 273 oncologists identified, four medical and two radiation oncologists were no longer practising and two radiation oncologists received surveys through both the COSA and RACR lists, leaving 265 eligible oncologists. Completed surveys were returned by 161 (61%) -- 60 radiation oncologists, 64 medical oncologists and 37 who could not be classified because they had destroyed the identifying number that allowed us to make this differentiation. Knowledge about non-traditional therapies Box 1 shows that meditation, relaxation and visual imagery were the therapies that most oncologists (about a quarter) reported knowing a lot about. Approximately a fifth of the oncologists surveyed also reported knowing a lot about antioxidant therapy and microwave, or Tronado, therapy. The least-known therapies were cellular therapy, magnetotherapy and psychic surgery. Perceptions of each therapy's potential harmfulness or helpfulness Box 2 shows that oncologists tended to consider the psychosocial therapies helpful for patients being treated both palliatively and curatively. Acupuncture was also considered helpful, especially for palliative patients. Many therapies were considered more likely to help palliative patients and, conversely, more harmful for curative patients. Not surprisingly, the less familiar, more physical or invasive therapies dominated those considered likely to be harmful. Perceptions of their patients' use of each therapy Box 3 compares the median proportion of their curative and palliative patients that oncologists believed were using or had used each non-traditional therapy with levels of use reported by Australian cancer patients.1-4 The oncologists showed a consistent trend to estimate higher use among palliative patients. The oncologists' estimates were within the ranges reported by Australian cancer patients for acupuncture, antioxidants, faith healing, hypnotherapy, iridology and meditation, relaxation and visual imagery. However, the oncologists overestimated patients' use of aromatherapy, coffee enemas, herbal therapies, naturopathy, homoeopathy, magnetotherapy and shark cartilage therapy. No patient data were available to compare cellular, mistletoe, microwave and ozone therapies or psychic surgery, and estimates for diet therapy were difficult to compare because of variation in the definitions used. Discussion As in the overseas studies,6,7 we found that oncologists identified gaps in their knowledge about many non-traditional therapies. It is interesting to note, however, that the therapies most patients reported using (meditation, relaxation and visual imagery and antioxidants) were also the therapies that most oncologists -- although still only up to a quarter -- reported knowing a lot about. Also consistent with the overseas studies,6,7 psychosocial therapies were viewed positively, and non-traditional therapies were considered more likely to be potentially helpful to patients being treated palliatively and potentially harmful to those being treated curatively. The more positive attitudes towards psychosocial therapies may reflect oncologists' awareness of some evidence of proven benefits from these therapies.8,9 Although our respondents tended to accurately estimate their patients' use of more commonly used non-traditional therapies, they tended to overestimate patients' use of more radical therapies, especially those with higher media profiles, such as coffee enemas and shark cartilage therapy. While the oncologists' and patients' estimates come from different surveys of different populations collected at different points in time, making some degree of variation inevitable, such variation is unlikely to explain the reasonably large differences for many of the lesser-used therapies. The trend for oncologists to estimate higher use of non-traditional therapies among palliative than curative patients is consistent with Australian and international data suggesting that patients with more advanced cancers are more likely to use non-traditional therapies.2,13-15 Our study has some other limitations. Firstly, for brevity, we sought no demographic information, thus prohibiting any assessment of the respondents' representativeness of Australian oncologists. However, as we targeted all Australian oncologists, and received responses from over 60% of the population, covering the full range of responses, we are confident that our data provide the first quantitative, reasonably representative overview of Australian oncologists' knowledge of and attitudes to non-traditional therapies. Secondly, we used self-report rather than an objective assessment of oncologists' actual knowledge about non-traditional therapies. As the oncologists are unlikely to have deliberately underestimated their knowledge levels, these estimates of how much they know should probably be interpreted as best-case scenarios. Also, we provided no definitions of "helpful" or "harmful", leaving individual oncologists to decide what constituted a harm or a help. This was done intentionally, as patients seek a range of benefits from non-traditional therapies, including physical, psychosocial and spiritual ones. Finally, while our results represent the first quantitative data on oncologists' knowledge and attitudes in this area, they cannot be generalised to other clinicians who treat people with cancer, such as surgeons, haematologists and general practitioners. Sceptics may question the need for oncologists to increase their knowledge about non-traditional therapies when the benefit of most remains unproven. However, without some basic knowledge of what is involved in each therapy, and of any demonstrated benefits or adverse reactions, oncologists may be unable to give adequate advice to patients. As outlined in the National Health and Medical Research Council guidelines, overly heavy-handed and dismissive attitudes are less likely to succeed in discouraging patients from using potentially harmful non-traditional therapies than more rational and considered discussions.5 Conclusions Research is needed to facilitate the production of evidence-based information summaries for oncologists in the area of non-traditional therapies, to compare oncologists' perceptions of use with their own patients' reported use of such therapies, and to establish the knowledge and attitudes of other clinicians treating cancer patients. Acknowledgements This research was funded by the NSW Cancer Council's Cancer Education Research Program. The views expressed are not necessarily those of the Cancer Council, which had no direct role in the design and/or analyses of this study or in the decision about publication of the results. We gratefully acknowledge the assistance of the Clinical Oncological Society of Australasia and the Royal Australasian College of Radiologists' (RACR) Faculty of Radiation Oncology for their assistance with identifying eligible oncologists, and the oncologists who completed the surveys. References Begbie SD, Kerestes ZL, Bell DR. Patterns of alternative medicine use by cancer patients. Med J Aust 1996; 165: 545-548. Miller M, Boyer MJ, Butow PN, et al. The use of unproven methods of treatment by cancer patients: frequency, expectations and cost. Supportive Care Cancer 1998; 6: 337-347. Yates PM, Beadle G, Clavarino A, et al. Patients with terminal cancer who use alternative therapies: their beliefs and practices. Sociol Health Illness 1993; 15: 199-216. Sawyer MG, Gannoni AF, Toogood IR, et al. The use of alternative therapies by children with cancer. Med J Aust 1994; 160: 320-322. National Health and Medical Research Council. Clinical practice guidelines: the management of early breast cancer. Sydney: The Stone Press; 1995. Crocetti E, Crotti N, Montella M, Musso M. Complementary medicine and oncologists' attitudes: A survey in Italy. Tumori 1996; 82: 539-542. Bourgeault IL. Physicians attitudes toward patients' use of alternative cancer therapies. Can Med Assoc J 1996; 155: 1679-1685. Meyer TJ, Mark MM. Effects of psychosocial interventions with adult cancer patients: a meta-analysis of randomized experiments. Health Psychol 1995; 14: 101-108. Devine EC, Westlake SK. The effects of psychoeducational care provided to adults with cancer: meta-analysis of 116 studies. Oncol Nurs Forum 1995; 22: 1369-1381. SAS [computer program], version 6.12. Cary, NC: SAS Institute Inc, 1998. Microsoft Excel [computer program], version 97. Seattle: Microsoft Corporation, 1997. Dobson AJ. Calculating sample size. Trans Menzies Found 1984; 7: 75-79. Risberg T, Lund E, Wist E. Use of non-proven therapies. Differences in attitudes between Norwegian patients with non-malignant disease and patients suffering from cancer. Acta Oncologica 1995; 34: 893-898. Sollner W, Zingg-Schir M, Rumpold G, Fritsch P. Attitude toward alternative therapy, compliance with standard treatment, and need for emotional support in patients with melanoma. Arch Dermatol 1997; 133: 316-321. Risberg T, Lund E, Wist E, et al. The use of non-proven therapy among patients treated in Norwegian oncological departments. A cross-sectional national multicentre study. Eur J Cancer 1995; 31A: 1785-1789. (Received 5 Jul, accepted 5 Nov, 1999) Authors' details NSW Cancer Council Cancer Education Research Program (CERP). Sallie Newell, PhD Research Academic (also Conjoint Lecturer, Discipline of Behavioural Science in Medicine, Faculty of Medicine and Health Sciences, University of Newcastle; currently Epidemiologist (Health Promotion Evaluation, Northern Rivers Institute for Health and Research, Lismore, NSW). Rob W Sanson-Fisher, PhD, Director (also Professor, Discipline of Behavioural Science in Medicine, Faculty of Medicine and Health Sciences, University of Newcastle; currently Dean of Faculty). Reprints will not be available from the authors. Correspondence: The Secretary, NSW Cancer Council Cancer Education Research Program, Locked Bag 10, Wallsend, NSW 2287. cherylmATmail.newcastle.edu.au Make a comment Back to text 2: Percentage of the 161 oncologists believing non-traditional therapies about which they reported at least some knowledge ("very little" or more) to be helpful or harmful Curative patients Palliative patients TherapyNo. reporting some knowledge of therapy*HelpfulHarmfulHelpfulHarmfulAcupuncture16025%1% 58%1%Antioxidants/high-dose vitamin C1605% 30%5%23%Aromatherapy1569%2% 21%1%Cellular therapy57029% 026%Coffee enemas1511%71% 1%70%Diet therapy (Gerson/macrobiotic)1422% 49%4%48%Faith healing/spiritualism15212%24% 23%15%Herbal therapies/naturopathy1598% 22%13%15%Homoeopathy1504%12% 8%6%Hypnotherapy15631%4% 46%3%Immune-enhancing therapy1313%27% 5%22%Iridology144 1%15%1%8%Iscador/mistletoe therapy1032%55% 2%45%Magnetotherapy695%8% 8%6%Meditation/relaxation/visual imagery15969% 3%82%2%Microwave/Tronado therapy1207%45% 7%37%Ozone therapy961%46% 2%37%Psychic surgery872%57% 2%56%Shark cartilage therapy1501%23% 1%17% *The remaining response options were "neither helpful nor harmful" and "don't know" - the balance of the oncologists with some knowledge of the therapy selected one of these options. Back to text 3: Perceptions among the 161 oncologists of their patients' use of non-traditional therapies compared with that reported by Australian cancer patients Oncologists' perceptions TherapyNo. reporting some knowledge of therapyMedian curative patientsMedian palliative patientsAcupuncture1606%10%Antioxidants/high-dose vitamin C16015%20%Aromatherapy1565%10%Cellular therapy573%3%Coffee enemas1513%5%Diet therapy (Gerson/macrobiotic)*14210%10%Faith healing/spiritualism1525%10%Herbal therapies/naturopathy15920%25%Homoeopathy15010%15%Hypnotherapy1565%5%Immune-enhancing therapy1315%8%Iridology1443%5%Iscador/mistletoe therapy1032%3%Magnetotherapy692%3%Meditation/relaxation/visual imagery15920%20%Microwave/Tronado therapy1201%1%Ozone therapy963%5%Psychic surgery871%1%Shark cartilage therapy1505%10% Reported use Therapy% Paediatric patients (n=48)4% Palliative patients (n=151)3% Medical oncology patients (n=319) 1% Medical oncology patients (n=156)2Acupuncture- 7%3%5%Antioxidants/high-dose vitamin C8%24%12%12%-16%Aromatherapy- --0.5%Cellular therapy----Coffee enemas---1%Diet therapy (Gerson/macrobiotic)*8%18%13%30%(diet therapy)(special foods)(diet therapy)(changed diet) 0.5% (Gerson)Faith healing/spiritualism6%9%7%3%Herbal therapies/naturopathy8%3%-8%6%5%-10%Homoeopathy2% 5%3%2%Hypnotherapy15%--3%Immune-enhancing therapy-3%4% -Iridology- --3%Iscador/mistletoe therapy----Magnetotherapy--- 0.5%Meditation/relaxtion/visual imagery4%-17%19%10%-13%12%-28%Microwave/Tornado therapy----Ozone therapy----Psychic surgery----Shark cartlilage therapy---4% *As diet therapies included those ranging from basic dietary changes through to very restricted diets (eg, Gerson diet), the actual wording used in each of the studies is included. 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Sallie Newell · Rob W Sanson-Fisher

The Centenary Institute of Cancer Medicine and Cell Biology The institute with the long name, short history, and tall goalposts Antony Basten Introduction - The first decade: - The second decade: - The future: the next decade - References - Authors' details - - More articles on Immunology and allergy Introduction As the joint centenaries of the University of Sydney's Medical School and its campus teaching hospital, Royal Prince Alfred Hospital (RPAH), crept closer in the early 1980s, a small group of clinical academics from medical, surgical, and obstetric specialties could be seen huddled together in corridors. What were they meeting about? asked their colleagues, exuding, as always, the paranoia and suspicion so common in academia. The answer soon became clear. Having trained and then exported, to other States and overseas, some of Australia's most talented researchers and clinical department heads, the time was ripe for the medical school and the hospital to reverse the New South Wales brain drain. The proposed mechanism was to be the creation on campus of a centre of excellence in medical research, akin to the successful Victorian institutes (the Walter and Eliza Hall, Baker and Howard Florey institutes) and the Garvan Institute in Sydney. The first decade: 1981-1989 The idea of a centre of excellence in medical research was warmly endorsed, not just by the university and hospital, but by the then Federal Liberal Government and the New South Wales State Labor Government, which jointly funded a feasibility study for construction of a research building, to accommodate 300 staff, adjacent to the medical school and hospital campus. In recognition of the need for a single major centre specialising in all aspects of cancer research and cell biology, the proposed institute received the name it still bears under an Act of the NSW Parliament: the Centenary Institute of Cancer Medicine and Cell Biology.1 Although failing to fit on any conference registration form, the name was intended to cover "all bases" -- in particular, to embody the concept that, to understand the abnormalities responsible for disease, the biology of normal cells must be studied first. In 1984, an Australian Science and Technology Council (ASTEC) Working Party2 reviewed the proposal and concluded that it was far too ambitious. The Working Party's verdict was that it was better to start small and build up slowly around a competitive research group. As a result, the wind was taken out of the Centenary Institute's sails and the project was becalmed for four long years. In retrospect, it is clear that this delay worked to the Institute's disadvantage in the long term. Instead of being established before the value of the specialised research centre was fully appreciated in NSW, its creation as a functional entity coincided with the rush to institute status by multiple groups on our own campus and elsewhere, leading ultimately to the current situation, with too many "institutes" competing for limited resources. In 1989, I was invited to be the inaugural Director of the Centenary Institute. At the time, as head of the Clinical Immunology Research Centre, one of the original 10 Commonwealth Centres of Excellence, I was trying to juggle exciting new research based on transgenic technology with the task of advising the Federal Government on medical and scientific aspects of HIV/AIDS. Little did I suspect, back then, that I would be jumping out of the frying pan into the fire. The second decade: 1989-1999 Early days The challenge in 1989 was to create an independent institute at a time of dwindling resources, both in the tertiary education sector and in the healthcare system. The Clinical Immunology Research Centre, operating from its crowded quarters in the 1880 building shared with other hospital and university staff, became the core unit of the Institute. We were faced with three formidable tasks. The first was to cope with the loss of our Centre of Excellence grant from the Australian Research Council, as funding for medical research centres was now deemed to be the responsibility of the National Health and Medical Research Council (NHMRC). Despite negotiating an increase in our NHMRC program grant, we were faced with an immediate loss of around $250 000 in research funding -- not the most auspicious start for a new institute. The second task was to appoint a new Board and Chairperson. A vigorous search, itself an experience for a naive academic like me, enabled us to secure the former Chairman of the Stock Exchange, Jim Bain, to chair the new Board. Under his stewardship, the Institute was steered through the next three difficult years and the Board established a Foundation, chaired by Tim Besley (Chairman of the Commonwealth Bank). The "Kick a Goal for Life" fundraising campaign, the brainchild of Ken Cowley (Chief Executive of News Ltd), a Foundation Trustee, gave us, for the first time, a public profile and much-needed funds. The campaign was launched to coincide with the final of the Commonwealth Bank Cup, awarded to the winners of the schoolboy rugby league competition. Alas, the number of on-field brawls reached such a pitch that the Commonwealth Bank promptly withdrew its support and our initial foray into the community came to an abrupt halt! The third vital task in 1989 was to obtain funding for a new building. Two further feasibility studies and six years later, four and a half floors of the Institute's new six-storey research facility were completed and fitted out at a cost of $17.24 million. This was funded largely from Federal and State capital works grants, with additional assistance from the NSW State Cancer Council and our two parent organisations, the University of Sydney and the Central Sydney Area Health Service. The Institute building is strategically located in the grounds of RPAH, adjacent to the university medical school, and was officially opened by the Prime Minister in 1997. The new team As the new edifice took shape, it was time to begin assembling a team of researchers with the skills to create a "critical mass" in immunology. My group, with its interest in self-tolerance in the B cell lineage, and that of Warwick Britton, head of a research program in mycobacterial infection, were already in place. Jon Sedgwick, well known for his work on autoimmunity in the central nervous system, was the first recruit from overseas. Described by the late Alan Williams of Oxford University as the best "postdoc" he had ever had, Jon was instrumental in grafting "knockout" (gene ablation) technology onto the Institute's existing expertise in transgenesis. Jon was followed by four other immunologists. Barbara Fazekas de St Groth, who, as a medical undergraduate, had done a BSc(Med) under my supervision a decade earlier, was the first. Returning to Sydney from postdoctoral study with Mark Davis at Stanford Medical School, Barbara is now recognised internationally for her work on tolerance and autoimmunity in T cell receptor transgenic models. Together with Patrick Bertolino, who joined us from Lyons in France two years ago, they make a formidable CD4+/CD8+ T cell team. Roland Scollay, known at the time as one of Australia's two leading exponents on thymus biology, was recruited from the Walter and Eliza Hall Institute, along with Phil Hodgkin from the John Curtin School of Medical Research in Canberra. Phil's recent studies on immune regulation and the relationship between division number and lymphocyte behaviour are among the most original contributions to immunology in the past five years. The final member of the quintet was Alan Baxter, who joined us from Cambridge (UK). Alan is rapidly acquiring an excellent international reputation in the field of insulin-dependent diabetes and the genetics of autoimmune diseases, including systemic lupus erythematosus and autoimmune gastritis (see Box). Achievements: the upside During the past decade, the staff has risen from 20 to 95; two NHMRC program grants have been held by research group heads; and the Institute, by virtue of its independent status, has brought to the campus more than $30 million in capital works and infrastructure funds, in addition to over $20 million in peer-reviewed grants. We were particularly delighted that Nobel laureate and immunologist, Peter Doherty, saw fit on the occasion of the official opening of the new building in 1997 to designate us as "Australia's major immunology research centre". A significant amount of the credit for these achievements must go to the Board and to Ken Tribe, its Chairman from 1994 to 1999. Ken brought to the Institute a wealth of knowledge and experience and gave us stable governance during this crucial period in our development. At the same time the work of the research staff has been underpinned by a dedicated research support and management team who have become past masters at maintaining an effective enterprise on the very shortest of shoestrings. Their loyalty and strength of purpose have been most gratifying to me personally. It has also been encouraging to work closely with the other four established independent institutes in NSW (the Garvan, Children's Medical Research, Prince of Wales Medical Research and Heart Research institutes) when negotiating with government and other bodies over issues such as infrastructure funding. The downside If one is honest there is inevitably a downside to any enterprise during its formative years and this has certainly applied to the Centenary Institute. Due to the delay already alluded to in "getting out of the blocks", the Institute has found itself competing for a dwindling pool of resources in the era of what cynics describe as the "epidemic of institutes". Some of them strive to be "independent" like us, while others are "motels" for existing academic and clinical staff or simply single departments renamed for the purpose of raising their profile and respectability. The end-result has been ongoing confusion among funding bodies, government, and even the community at large about who is most deserving of support. The consequence for the well intentioned Director and staff of the Centenary Institute was that when the new building opened they faced a hostile reception on campus, particularly from colleagues who were short of funds and research space. They saw our hard-earned new building as the answer to their prayers, while failing to appreciate our statutory charter and independent status. If only the building had not resembled a casino! Like all of the fledgling independent research centres which have emerged during the recent "epidemic", the Centenary Institute has had to deal with three major issues: inadequate infrastructure, limited funds for developing new groups of merit, and insufficient job security (not to mention salaries) for our full-time career scientists. Perhaps of greatest concern is the fact that the days when one can offer "fame and poverty" to the very best researchers, as Fiona Stanley so aptly put it, are dwindling fast.3 This was driven home to me when two of our most senior group heads were lured to the United States by the offer, not just of much higher salaries, but of far better resources. "If only I did not have to write so many grants for such pathetic amounts of money I would actually have time to do some research", Jon Sedgwick said to me before his departure. The future: the next decade Medical research in Australia Do institutes, independent or otherwise, have a future, or are they likely to acquire the same mortality rate as the biotechnology companies of yesteryear? I believe that some institutes like ours must survive and flourish if Australian medicine is to retain its place at the international table. We have clearly moved into the era of specialisation, in which it is quite acceptable to be recognised as a superb teacher or clinician or researcher, but what is no longer feasible is to be good at every aspect of medicine. The role of institutes, with their critical mass of full-time research staff, is to serve as a focus for collaborative research on the campuses of teaching hospitals and universities with which they are usually affiliated. It is timely that the Wills Review4 has just been published, coinciding as it does with the Federal Government's most welcome commitment to doubling NHMRC funding over the next five to six years. Not only does the Review promote competitive research by extending the concept of partnerships to both Government itself and industry, but it contains a series of innovative recipes which acknowledge the value of the independent institute as a research entity in Australia and of the full-time career scientist. Its implementation is therefore eagerly awaited, particularly by the 30-odd members of the Association of Australian Medical Research Institutes, which between them employ over 2500 research staff. In response to the Wills Review, the challenge for all of us in the medical research community is to secure sufficient ongoing funds to ensure that its recommendations bear fruit. In the case of an institute like ours, this means adding to the existing infrastructural support from the NSW State Government and the Central Sydney Area Health Service by raising funds in the non-Government sector, including from industry and the corporate and wider communities. While creating a public profile and exploiting research are anathema to the purists of the research world, the reality is that the rest of society expects to know about us if they are going to provide the financial support we urgently need. Medical research at the Centenary Institute Having commissioned a new building and recruited high-quality staff, the Institute is now poised to complete the final stage of its 10-year strategic plan. The goal is to create a second critical mass of career researchers in molecular and cellular oncology. A major step forward occurred earlier this year when a $6 million funding package was approved by the Prime Minister. The package is designed to support a strategic alliance with the Sydney Cancer Centre, whereby the Institute would develop a basic cancer research program in the remaining one and a half floors of our building to dovetail with translational and clinical research studies at the Sydney Cancer Centre, located on the adjacent RPAH campus. The first move towards this collaboration has now been made, with the conjoint appointment of John Rasko, a haematologist, who has returned to his old alma mater from the Fred Hutchinson Cancer Research Center in Seattle to head up the Institute's gene therapy laboratory (see Box). The combination of our brand of cellular immunology (traditionally one of Australia's strongest disciplines) with molecular biology targeted at cancer is designed to give the Institute a discrete niche in the postgenomic era now upon us. Edward Jenner as the role model On reading an article recently about the famous country general practitioner, Edward Jenner,5 I rapidly perceived that he was the ideal role model for the institute director of the future. Jenner, famous for his discovery of smallpox vaccination, had other admirable but lesser-known attributes, including an entrepreneurial flair for raising funds, a fascination with diverse areas of science, and proficiency as a poet and musician. When the veracity of his findings on smallpox was being disputed by the inevitable envious colleagues in the United Kingdom and the United States, he raised funds from the public to extend his work (in the absence of any NHMRC equivalent). Later in his life he demanded and received special grants, the first of no less than £10 000, from the government of the day in Great Britain to compensate for the expenses incurred by his research and to set up free vaccination clinics for the public. In 1789 he was elected to the Royal Society, not for his work on vaccination, but rather for his authoritative studies on the habits of the cuckoo nestling. He also found time to classify the botanical specimens brought back by Joseph Banks from James Cook's second voyage to Australia. Despite working full-time on his research, Jenner managed to raise funds and remain a civilised human being. How wonderful it would be for those of us who are institute directors to aspire to just one or two of his many attributes. References Centenary Institute of Cancer Medicine and Cell Biology Act 1985 (NSW). Australian Science and Technology Council. Annual Report 1983-1984. Appendix C. Canberra: AGPS, 1984: 30-36. Stanley FJ. The TVW Telethon Institute for Child Health Research: the birth and growth of a research institute. Med J Aust 1998; 169: 630-633. Wills PJ (Chairman). Health and Medical Strategic Review. The virtuous cycle: working together for health and medical research. Canberra: Department of Health and Aged Care, 1999. Friedman M, Friedland GW. Edward Jenner and vaccination. In: Medicine's 10 greatest discoveries. New Haven: Yale University Press, 1998: 65-93. Authors' details Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW. Antony Basten, AO, FAA, FTSE, Executive Director. Reprints: Professor A Basten, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag 6, Newtown, NSW 2042. a.bastenATcentenary.usyd.edu.au Prime Minister John Howard (center) with Professor Peter Doherty (right) and Professor Antony Basten (left) at the offical opening of the Institute's new building in 1997. The original headquarters of the Centenary Institute located in multipurpose building 94 at the Royal Prince Alfred Hospital. The new Institute building commissioned in 1994. The Centenary Institute of Cancer Medicine and Cell Biology at a glance YearCorporate milestonesResearch milestones 1985Established under an Act of the NSW Parliament as an independent institute with its own Board of Governors and affiliated with the University of Sydney and RPAH 1989Became a functional entity with appointment of Professor Tony Basten as Director and Mr Jim Bain as Chairman of the Board Staff of 20. Director's Clinical Immunology Research Centre became core unit of Institute, comprising his B cell Biology Group and Mycobacterial Research Group (Associate Professor Warwick Britton, University of Sydney) 1991Creation of Foundation with Mr Tim Besley (Chairman), Mr Ken Cowley and Mr Tony Berg as trustees Became a Member Institute of AMRAD Immunopathology Group (Dr Jon Sedgwick, Wellcome Trust SRF)† NHMRC Program Grant to Director renewed 1992Devolved from management of University Appointment of General Manager (Denyse Bartimote) Capital works funding of $17.24 million obtained for new building T cell Biology Group (Dr Barbara Fazekas de St Groth, Wellcome Trust SRF) Thymus Biology Group (Dr Roland Scollay, NHMRC SPRF)† 1994Mr Ken Tribe appointed Chairman of the Board 1995Four and a half floors of new six-storey building commissionedImmune Regulation Group (Dr Phil Hodgkin, Medical Foundation SRF) Liver Immunobiology Group (Professor Geoff McCaughan, RPAH) 1997New building officially opened by Prime Minister New research and development infrastructure funding scheme introduced by State Health Department, providing Institute with $800000 per annumAutoimmunity Research Group (Dr Alan Baxter, NHMRC R Douglas Wright Research Fellow) 1998NHMRC Program Grant in diabetes (Alan Baxter co-chief investigator) 1999$6 million package announced by Prime Minister for joint cancer research program with Sydney Cancer Centre, RPAH Mr Malcolm Noad appointed Chairman of the Board Total staff of 95 Gene Therapy Research Group (Dr John Rasko) Total funding brought to the campus by the Institute was in excess of $50 million *For further details on research programs refer to web site <http://www.centenary.usyd.edu.au> †Left Institute to take up position in United States NHMRC = National Health and Medical Research Council. RPAH = Royal Prince Alfred Hospital. SPRF = Senior Principal Research Fellow. SRF = Senior Research Fellow.

Antony Basten

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. 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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