Cancer

Objective: To examine long-term trends in cancer mortality in the Indigenous people of the Northern Territory (NT) of Australia.Design: Comparison of cancer mortality rates of the NT Indigenous population with those of the total Australian population for 1991–2000, and examination of time trends in cancer mortality rates in the NT Indigenous population, 1977–2000.Participants: NT Indigenous and total Australian populations, 1977–2000.Main outcome measures: Cancer mortality rate ratios and percentage change in annual mortality rates.Results: The NT Indigenous cancer mortality rate was higher than the total Australian rate for cancers of the liver, lungs, uterus, cervix and thyroid, and, in younger people only, for cancers of the oropharynx, oesophagus and pancreas. NT Indigenous mortality rates were lower than the total Australian rates for renal cancers and melanoma and, in older people only, for cancers of the prostate and bowel. Differences between Indigenous and total Australian cancer mortality rates were more pronounced among those aged under 64 years for most cancers. NT Indigenous cancer mortality rates increased over the 24-year period for cancers of the oropharynx, pancreas and lung, all of which are smoking-related cancers.Conclusions: Cancer is an important and increasing health problem for Indigenous Australians. Cancers that affect Indigenous Australians to a greater extent than other Australians are largely preventable (eg, through smoking cessation, Pap smear programs and hepatitis B vaccination).

John R Condon MPH, FAFPHM, PhD Student · Joan Cunningham ScD · Tony Barnes MSc · Bruce K Armstrong DPhil

Alex J Chamberlain,* John W Kelly† * Registrar, † Head, Victorian Melanoma Service, The Alfred, Prahran, VIC. alex_chamberlainAThotmail.com To the Editor: Janda and colleagues’ survey of skin screening by general practitioners in regional Queensland1 demonstrated that only 20% of participants had undergone a total-body skin examination in the previous 3 years and that examination rates were slightly lower for patients 50 years of age and older. They conclude that those at greatest risk (older people, especially men) will need to be targeted if screening programs are to reduce melanoma mortality. In the same issue of the Journal, a study by English and colleagues of excisional biopsies of pigmented lesions by Perth GPs showed that the excision rate for patients under the age of 50 years (62%) is nearly twice that for patients over 50 years (38%), and that in the younger cohort this is primarily harvesting benign naevi.2 They conclude by encouraging GPs to increase their suspicion and lower their biopsy threshold in older patients in order to detect more melanomas. These studies serve to remind us that it is predominantly older people (and especially men) who are at greatest risk of thick (and potentially lethal) melanoma.3 The evidence provided by these studies of mismatch between skin cancer risk and resource allocation to surveillance and excisional surgery might help explain why recent advances in early detection seem to have bypassed elderly men. It is of continuing concern that despite the fact that melanomas are currently diagnosed at an earlier stage when compared with 20 or 30 years ago, the background incidence of thick melanoma has remained stable, both in Australia and around the world. In a recent study conducted in Victoria,4 we found that thick melanomas (≥ 3 mm) were predominantly nodular melanomas, primarily affecting people over 50 years of age and especially men. This elusive subtype frequently fails to fulfil the “ABCD” (asymmetry, border, colour, diameter) diagnostic criteria in that they are more often uniform in colour, symmetric in shape and predominantly amelanotic.5 A possible aide-mémoire that we have suggested elsewhere for identifying nodular melanoma is the addition of “EFG” (“elevated, firm, growing for more than 1 month”) criteria.6 The observation that nodular melanomas grow quickly, leading to deep invasion within a few months, poses a significant obstacle to the potential success of community-based screening programs.1 It is likely that many nodular melanomas will escape early detection by such programs, as they will evolve significantly in the interval between screening examinations.4,5 It is important that all clinicians recognise this subtype if we hope to reduce melanoma mortality in Australia.

Alex J Chamberlain · John W Kelly

Can chemoprevention reduce the risk of progression to malignancy? Once a rare tumour, adenocarcinoma of the oesophagus has tripled in incidence in Australia over the past 20 years (Ian McDermid, Australian Institute of Health and Welfare, personal communication). This increase, together with the dismal 5-year survival of patients with this cancer, has focused attention on its risk factors. The strongest of these are symptomatic gastro-oesophageal reflux disease and Barrett’s oesophagus, a condition in which the squamous lining of the lower oesophagus is replaced by metaplastic columnar epithelium. Based on postmortem studies, Barrett’s oesophagus probably affects about 1% of the population in the United States and, at endoscopy, one in five to 10 patients with gastro-oesophageal reflux.1 Evidence of Barrett’s oesophagus (or at least intestinal metaplasia) is commonly found in resection specimens for oesophageal cancer.1 When Barrett’s oesophagus is found at endoscopy, the appropriateness of the patient entering a surveillance program may be considered, with the aim of reducing the risk of death from oesophageal adenocarcinoma. These programs involve regular endoscopy with multiple biopsies from the metaplastic epithelium and interpretation by a skilled pathologist. The rate at which malignancy develops in patients undergoing surveillance has been overestimated in the past because of publication bias; a reasonable estimate appears to be about 1 tumour in 200 patient-years of surveillance.2 The absolute lifetime risk of an individual with Barrett’s oesophagus developing oesophageal adenocarcinoma is probably about 1 in 20, which is comparable to the community risk for developing colorectal cancer. The average age for developing oesophageal adenocarcinoma is the mid to late 60s, but only a few patients with Barrett’s oesophagus die of oesophageal cancer, as comorbidities are common.3 Given these facts, and the problem of ensuring compliance with surveillance, it is not surprising that it has been difficult to demonstrate that surveillance programs reduce mortality, either overall or from oesophageal cancer. The only positive evidence that surveillance improves outcomes derives from the results of surgery on patients with surveillance-detected tumours. These patients generally fare better than those who are diagnosed after presenting with symptoms. Although individual patients may benefit from surveillance, the overall community benefit and cost-effectiveness of these programs is still debated (particularly for programs not conducted in well organised centres by enthusiasts with access to specialist pathologists).4 The use of biomarkers, such as aneuploidy or molecular markers, may help predict the risk of malignancy and may be useful in targeting surveillance programs.5 If surveillance of patients with Barrett’s oesophagus is unrewarding, are there ways to retard the neoplastic process? Recently, the pathobiology of Barrett’s oesophagus has come under intense scrutiny, and it is likely that repeated exposure of the lower oesophagus to reflux of acid and bile is a major factor resulting in metaplasia and subsequent dysplasia.6 Molecular changes in the pathway to malignancy have been identified, including upregulation of cyclo-oxygenase-2 (COX-2).7 The study reported by Hillman and colleagues in this issue of the Journal (page 387) examines the effect of acid suppression on the development of dysplasia in Barrett’s oesophagus.8 The authors analysed the pathology findings from a group of patients enrolled in a surveillance program over the period of time during which proton-pump inhibitors (PPIs) were introduced. The rates of development of dysplasia and malignancy were examined before and after patients started taking PPIs. Although the results must be interpreted in the light of the lack of randomisation, the time effects, and difficulties in distinguishing low-grade dysplasia from inflammatory atypia (problems which the authors recognised and corrected for as far as possible), the study does demonstrate an effect of acid suppression on the development of dysplasia and malignancy. Over 50% of patients (a somewhat high figure) developed low-grade dysplasia within 3 years while not taking PPIs, but this percentage was reduced by almost two-thirds in patients taking PPIs. Interestingly, the dysplasia-free survival curves diverged after only months, suggesting that the effect was rapid. If acid suppression were efficacious in reducing the risk of malignancy, it would be an attractive chemopreventive option, as: it is the cornerstone of therapy for gastro-oesophageal reflux disease, with which Barrett’s oesophagus is closely associated; powerful acid-suppressant drugs are available; and a reduction in gastric acid exposure leads to a concomitant reduction in bile exposure. Combining acid suppression with COX inhibitors (especially aspirin) has further attractions, as COX inhibition alone may reduce the incidence of oesophageal carcinoma by up to half,9 and some of its risks would be ameliorated by acid suppression. COX inhibitors may have an additional benefit on cardiovascular risk in this group of patients. Studies to investigate these issues are under way. So how will this information help us control oesophageal adenocarcinoma? In particular, if acid suppression does reduce the rate of progression of Barrett’s oesophagus to low-grade dysplasia, will this translate into a reduction in the incidence of oesophageal adenocarcinoma? The natural history of low-grade dysplasia is not well defined, while even that of high-grade dysplasia has been debated,10 with the estimated cumulative incidence of cancer varying dramatically between studies, from 56% at 3 years to only 9% at 5 years. The most efficacious method of preventing gastro-oesophageal reflux is good antireflux surgery, so, if control of acid and bile reflux alone were the answer, one might expect to see a dramatic reduction in the rate of oesophageal adenocarcinoma after fundoplication. Unfortunately, this has not been the case.11 One might also predict that the increasing use of proton-pump inhibitors in the past decade, and particularly in the past few years, would reduce the rate of oesophageal adenocarcinoma. However, this effect is not yet evident either in follow-up of patients prescribed omeprazole,12 or in national cancer monitoring (Ian McDermid, Australian Institute of Health and Welfare, personal communication). Even if chemoprevention using potent acid suppression, with or without COX inhibition, can be shown to slow development of malignancy, given the modest absolute risks (1 per 20 patients with Barrett’s oesophagus and perhaps 1 per 200 of those with gastro-oesophageal reflux), we must still identify and target appropriate groups for this or other interventions. We must also carefully examine strategies for efficacy and cost effectiveness. Low-risk strategies, such as chemoprevention, may be broadly applicable, whereas intensive strategies, such as endoscopic surveillance with examination of biopsy specimens for biomarkers of malignancy, will need to be targeted to high-risk groups.13 The jury is still out.

Geoffrey S Hebbard PhD, FRACP · Sanjay Nandurkar FRACP

The debate over prostate-specific antigen (PSA) testing for prostate cancer has been prolonged, public, and sometimes acrimonious. Despite this, a common theme is present in most evidence-based guidelines produced to date: while population-based screening cannot be advocated currently, individuals considering a test should be fully informed about the pros and cons and make their own decisions. 1-3 The US Preventive Services Taskforce adds that individuals “be assisted in considering their personal preference and risk profile”.4 However, none of these guidelines address the issue of how to ensure such “informed choice”. * The Australian Prostate Cancer Collaboration is a national organisation of clinicians, researchers, consumers and non-government organisations with an interest in prostate cancer. It receives project-based sponsorship from non-government organisations and commercial sources. The Australian Prostate Cancer Collaboration* (APCC), with support from the National Cancer Control Initiative, convened a workshop on informed choice for prostate cancer testing. The meeting was part of the Conjoint 4th National Prostate Cancer Symposium and the 5th Annual APCC Meeting held at Royal Melbourne Hospital in August 2003. The workshop participants (about 50 people) comprised urologists, GPs, nurses, members of non-government cancer organisations, patients and consumers. The diverse views presented at the workshop suggested that an active approach to managing the PSA testing issue in general practice is needed. What is currently happening?Jeanette Ward (Director, Division of Population Health, South West Area Health Service) summarised the current status — that PSA testing is widespread in general practice (in a Western Australian study, 48% of men aged 45 to 60 years had ever been tested).5 Furthermore, men overestimate their risk and make decisions without being fully informed. 5-7 Max Gardner (Chair, Prostate Cancer Foundation of Australia) and several workshop attendees made it clear that some men with prostate cancer felt they did not have an opportunity for informed testing when their cancer may have been localised. Paul Nisselle (Health-Law Consultant; formerly Chief Executive, Medical Indemnity Protection Society and general practitioner) described the medicolegal exposure arising from this situation, as well as when men feel that they have been harmed by unnecessary screening. A common theme was that a climate of anger, frustration and, increasingly, litigation is arising from men feeling inadequately informed about prostate cancer testing. Addressing this issue, speakers described barriers that prevent men being fully informed. These include: time constraints for the GP; lack of knowledge of the issues (Murray Barson, general practitioner with interest in men’s health; Debra Rowett, Chief Investigator, DATIS trial of academic detailing for PSA testing in general practice); lack of understanding of medicolegal obligations, particularly what is prudent and what is sufficient in terms of information provision (Nisselle); and wide ranges in patients’ awareness, concerns, levels of comprehension and life circumstances (Barson; Suzanne Steginga, Director, Community Services, Queensland Cancer Fund). Lack of understanding of how to communicate the complex areas of risk and uncertainty (Barson; Rowett; Ward) is also a barrier to fully informing men. What constitutes “informed choice”?Niselle revisited the medicolegal precedent set by Rogers v Whitaker and suggested that three tests are needed to determine if a patient has been fully informed: The reasonable patient test: information has been given that a reasonable person as a patient would think relevant; The reasonable doctor test: extra information has been given, which a reasonable doctor would add, having regard to the particular circumstances of the patient; and The individual patient test: additional information has been given, that that particular patient sought, having been given the opportunity to seek it. “Informed refusal” is as important as “informed consent”. A patient needs to be made aware that there is information he should consider before deciding not to have a test. How patients make decisions is crucial in determining how they should be informed. Steginga reported research which suggests that patients more commonly use non-systematic processes (eg, anecdotes or analogies, old beliefs, salient experiences and expert opinion) to make health-related decisions rather than systematic processing (the weighing up of the medical risks and benefits of the decision). As a consequence of these issues, Nisselle and Steginga maintained that providing a patient with written material and telling him to go away and make a decision is not enough. A discussion between doctor and patient has to take place, in which the patient’s views and beliefs are elicited, medical information is individualised to the patient’s circumstances (eg, age, family history), and the patient’s specific information needs are responded to. In short, “shared decision-making”. Pinnock outlined effective communication strategies to support this shared decision-making. These include establishing the preferred amount of information, the preferred role in decision-making,8 graphical representations of risk, and checking patient understanding. Ward noted that preference for a shared decision-making has been found in studies of men and GPs alike.9 Rowett reported results from the DATIS trial (a three-state study of academic detailing, which is a form of educational outreach as a means of informing GPs about issues concerning prostate cancer screening). Unprompted comments from GPs suggested that, although secondary, written materials can be useful in supporting the discussion. This was reinforced by Ward,9 who found that written materials increased knowledge gain by patients, particularly in those who prefer an active decision role. Pinnock discussed quality criteria for decision aids,10 including neutral framing, explicit evidence base, and evidence of effectiveness. High-quality written materials may reduce the length of the consultation (Rowett), improve patient knowledge,9 and reduce decisional conflict,9 but their effect on the decision outcome is variable (Steginga). The content of the informed-choice discussionGardner (providing a patient perspective), Pinnock (from the perspective of published research), and Ward (based on her group’s research) addressed the categories of information that should be presented in written materials. These include: Basic information on the prostate and its function, the individualised risk of developing prostate cancer and dying from it, and the way in which the man’s age, health status and family history may modify these risks; The potential benefits of early detection (can detect disease at a stage when treatment is potentially curative) and uncertainties (not sure whether active treatment prolongs life); and The performance of the PSA test in detecting prostate cancer (sensitivity, specificity and positive predictive value).9 The outcome of informed choicePinnock suggested that the outcome of this process of discussion and decision support is not a decision whether or not to test, but a management plan, which may involve review only, a single test, or testing at specified intervals. It should be individualised to the patient’s situation, sense of his risk, and preference when balancing the potential benefits, risks and uncertainties of early detection for prostate cancer. Providing resources and skills to GPsThe DATIS study suggests that academic detailing is successful in reaching GPs (80%–90% penetration), acceptable to GPs, and effective in increasing knowledge and perceived ability to inform patients. Ward revealed that a NSW trial of a peer-led 3-month education program will also look for improvements in understanding the evidence, perceived medicolegal risk and self-efficacy in promoting informed decision-making. Improved health literacy schemes in the community may reduce GP time required to explain basic background information. Furthermore, improving prostate health literacy is likely to improve decision-making regarding lower urinary tract symptoms,11 which are more common than prostate cancer. Sharing the educational task with non-government organisations, such as cancer councils, could spread the cost across sectors. These and other strategies to make the informed-choice discussion time-efficient need to be explored. Addressing inequity in accessWorkshop attendees raised the issue of men who are unconcerned about their health, who do not visit their doctor, and others (eg, rural men), who have poor access to medical services. These groups have an imposed, or default, uninformed refusal of prostate cancer testing. Education programs targeting general practice will not address this problem, but a community education program can reach such groups. Community education focusing on male reproductive and prostate health is also likely to promote a more active role for men in maintaining their health and reduce stigma associated with some of these disorders. Should this wait until 2008?Two speakers (Pinnock; Greg Neerhut, urologist, Victoria) addressed whether the need for informed choice will change once the results of the US and European randomised controlled trials on prostate cancer screening become available from 2008. Even if a screening benefit is detected in trials, the need for a man to make a fully informed decision will remain. This is because any survival benefit of active treatment of localised disease is likely to be evident only after 10 years or more.12 It is also likely that the poor performance of the PSA test, in particular the high rate of false positive results, will continue or increase with widespread early detection. In summary, the workshop established that there is a pressing need to support and resource GPs assisting men in making an informed choice about prostate cancer testing, to disseminate knowledge of how patients make these decisions, medicolegal issues, and provide access to decision support resources. A community education program on men’s prostate or reproductive health will help to reduce the burden on the GP as the sole agent responsible for community and patient understanding of these issues.

Carole B Pinnock PhD

Objective: To examine whether proton-pump inhibitor (PPI) therapy influences the incidence and progression of dysplasia in patients with Barrett’s oesophagus.Design and setting: Review of prospective data on patients undergoing surveillance with regular endoscopy and biopsy at a private endoscopy centre in Canberra, ACT, between 1981 and 2001.Patients: 350 patients diagnosed with Barrett’s oesophagus.Interventions: PPI therapy was progressively introduced into clinical practice from late 1989. Once begun, PPI therapy was ongoing, with no attempt to reduce the dose.Main outcome measures: Relationship between development of dysplasia or adenocarcinoma and delay between diagnosis with Barrett’s oesophagus and starting PPI therapy was determined by Cox regression analyses, stratified by year of enrolment. Age, sex, presence of macroscopic markers (severe oesophagitis, nodularity, Barrett’s ulcer, stricture) and use of aspirin or non-steroidal anti-inflammatory drugs were considered as confounding factors in the regression analyses.Results: The 350 patients had 1422 surveillance endoscopies, with a median follow-up of 4.7 years. Patients who delayed using a PPI for 2 years or more after diagnosis with Barrett’s oesophagus had 5.6 times (95% CI, 2.0–15.7) the risk of developing low-grade dysplasia at any given time as those who used a PPI in the first year. Similar results were found for the risk of developing high-grade dysplasia or adenocarcinoma (hazard ratio, 20.9; 95% CI, 2.8–158).Conclusions: Use of ongoing PPI therapy appeared beneficial in the prevention of dysplasia and adenocarcinoma in patients with Barrett’s oesophagus. We suggest that all patients with this condition, even those with no oesophagitis or symptoms, should be encouraged to continue long term PPI therapy.

Lybus C Hillman MD, FRACP · Louise Chiragakis MA · Graham L Kaye FRACP · Anthony C Clarke FRCP, FRACP · Bruce Shadbolt PhD

Michael A Quinn Director, Oncology and Dysplasia Unit, Royal Women's Hospital, 5th Floor, 132 Grattan Street, Carlton, VIC 3053. michael.quinnATmaynegroup.com To the Editor: A recent article by Zorbas et al1 highlights some of the many difficulties experienced by Australian women in accessing multidisciplinary care after they have been diagnosed with breast cancer. A multidisciplinary approach to women with gynaecological cancer has been the cornerstone of care since the establishment of gynaecologic oncology units in Australia in the early 1980s. Over 20 years’ experience has reinforced the value of this approach. By and large, however, the success of this model has very much depended not only on the skills of the multidisciplinary team but also on the readiness of referring doctors — in this case, specialist gynaecologists — to refer patients for management that is often surgical and could easily be done by themselves. Reinforcing the concept that care of the patient is holistic and that surgery plays an important (but not definitive) role in overall care has led to increased referrals, but there are still many to convince. For instance, a survey published in the Journal in 20022 showed that in the late 1990s more than half the women with ovarian cancer in Victoria were still being operated on outside established gynaecologic oncology units or by a non-gynaecological oncologist. It is to be hoped that new National Health and Medical Research Council guidelines on the management of ovarian cancer (soon to be released) will reduce this deficit and thereby improve outcomes for women with ovarian cancer. Much of the development of this benchmark care has come from patients, who, thankfully, are becoming increasingly articulate in their expectations of optimal clinical outcomes. The question of rural patients is an extremely important one. In Victoria, over a period of more than 10 years, the three major metropolitan gynaecologic oncology centres have established satellite clinics in country towns to facilitate patient follow-up, often involving local specialists and family doctors. This system seems to have worked well and is worthy of assessment as a model that might be transferable to other specialties. In conclusion, it is all very well setting up multidisciplinary teams, but the key to their success has to be the recognition of professional equality. If teams are based on a hierarchical setup they are likely to fail in their major aim, which is to provide the best care available based on input from a broad range of professionals and from patients themselves.

Michael A Quinn

Susan C Pendlebury,* Katherine J Clark,† Martin H N Tattersall‡ * Radiation Oncologist, † Palliative Care Physician, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050; ‡ Professor of Cancer Medicine, University of Sydney, Sydney, NSW. spendlebATemail.cs.nsw.gov.au To the Editor: Zorbas et al1 have highlighted both the complexities and resource intensiveness of multidisciplinary care for women with early-stage breast cancer. The same arguments exist in advanced disease, where input from many disciplines is the norm. However, there is no evidence that such a process improves outcomes in the Australian setting. The references the authors draw upon relate to regions in which breast cancer outcomes have historically been poor. Evidence from Australian studies suggests higher standards of care and appropriate changes over time. 2,3,4 The National Health and Medical Research Council (NHMRC) Clinical practice guidelines for the management of early breast cancer5 provide an evidence-based strategy for managing the disease. Enshrined within them is the concept that many different treatment approaches are equivalent and that patient preferences are important. Patient input into multidisciplinary case conferences is frequently minimal. Case conferences can be confusing for patients, and it may not be clear to them who is their doctor. Many clinics include a breast nurse, who commonly acts as a patient advocate. Zorbas and colleagues note the different models of multidisciplinary care, but the minimum approach required to achieve good outcomes has not been established. It is not surprising that 34% of rural surgeons find it difficult to implement a service in which all women have access to a full range of treatment options in a multidisciplinary setting. There is no evidence, however, that their patients are more unhappy or that management outcomes are inferior. Similarly, the guidelines correctly promote the importance of psychosocial support for patients, but the suggestion that this can be better achieved by a psychologist via teleconferencing rather than by the patient’s general practitioner is purely speculative. None of the multidisciplinary models suggested by Zorbas et al addresses the management of patients at relapse, and yet data and clinical experience indicate this is the time of greatest stress for patients, 6 a time when input from a number of specialties — medical care, radiation oncology, palliative care — is the norm. Multidisciplinary care appears to be beneficial regardless of the stage of disease. However, the execution of some of the models is resource-intensive. We need to evaluate not only whether the objectives of the NHMRC guidelines are met, but whether patient satisfaction and participation are enhanced, survival outcomes are improved and care through all stages of the disease is optimal. Currently, by such measures, multidisciplinary care has not been shown to be superior to a small number of well-directed, evidence-based selective consultations.

Susan C Pendlebury · Katherine J Clark · Martin H N Tattersall

Helen M Zorbas,* Bruce H Barraclough,† Katherine J Rainbird,‡ Karen A Luxford,§ Sally Redman¶ * Clinical Director, ‡ Manager, Treatment Program, § Program Director, National Breast Cancer Centre, Locked Bag 16, Camperdown, NSW 1450; † Director of Cancer Services, Department of Surgery, Royal North Shore Hospital, St Leonards, NSW; ¶ Director, Institute for Health Research, Sydney, NSW. karenlATnbcc.org.au In reply: We agree with the comments by Pendlebury et al that knowledge about outcomes for patients receiving multidisciplinary care in Australia is limited. Hence, the National Breast Cancer Centre has investigated the application of multidisciplinary care and outcomes for women with breast cancer. Our article focused on the “Principles of multidisciplinary care” developed as a basis for a subsequent project (outcomes yet to be published). It was necessary to define such principles at the outset, as there is not yet an agreed view about what constitutes “multidisciplinary care” within the Australian healthcare context. We also agree that the standard of clinical care in Australia is generally good. However, delivery of care is often fragmented and inconsistent.1 In other countries with high quality services, multidisciplinary meetings have been found to result in care that is more in accord with the evidence than non-multidisciplinary care.2 The Principles emphasise the role of the general practitioner, while recognising that some patients will require appropriate specialist referral.3 They also state that living in a rural area should be no impediment to accessing care. We agree that multidisciplinary care is as important in advanced breast cancer as it is in early disease. The Principles were developed before the release of the guidelines for advanced breast cancer and it would be useful to extend them in the future. The importance of one main contact for women is acknowledged. The purpose of a multidisciplinary case conference is to identify treatment options and their relative merits. This ought to assist communication with women and enable them to make a more informed choice.

Helen M Zorbas · Bruce H Barraclough · Katherine J Rainbird · Karen A Luxford · Sally Redman

The South Australian Workers Compensation Tribunal has found that stress contributed to a man’s colorectal cancer. The medical evidence for this is very limited, and the case highlights the difference between scientific and legal proof. The South Australian Workers Compensation Tribunal has concluded, on the basis of the evidence presented to it, that workplace stress contributed to the development of colorectal cancer in a prison officer.1 This finding highlights the role of the adversarial legal system, in which courts and tribunals are generally limited by the material the parties choose to present.2 However, this subtlety was not reflected in the subsequent media coverage, with headlines such as “Work and stress — judge finds a deathly link” and lines such as “A judge has accepted that a prison officer’s job stress contributed to the cancer that killed him in a ruling that threatens to unleash a series of cases . . .”.3 It is therefore pertinent to review the medical history on which the decision was based and the medical literature to see whether this putative link should be challenged, despite the lack of an appeal by the South Australian Crown Solicitor’s Office.3 Medical historyThe prison officer was employed by the South Australian Department of Correctional Services for 21 years, from 1977 to 1998. A diagnosis of colorectal cancer, resulting in resection of an advanced colon cancer of the caecum (Dukes’ C stage), was made at age 59 years, and the man died in 1998 aged 60 years. The prison officer’s father had died of colorectal cancer when 75 years old, with age at onset of his cancer unknown. The Tribunal noted the influence of inheritance in the development of colorectal cancer, but several factors invite comment. First, there is no indication whether a detailed family history had been obtained, for example by a family cancer service. It is well documented that history-taking by individual practitioners misses a substantial number of relatives affected by cancer.4,5 Moreover, the decision does not indicate whether the cancer tissue was submitted for genetic testing, which could provide objective evidence of inherited risk through immunohistochemistry and microsatellite instability testing.6 Medical literature reviewThe Tribunal described the “considerable examination of relevant literature” by the various medical experts as a key dimension of the case.1 Four main studies were cited.7-10 One study compared 551 individuals with colorectal cancer with 1861 controls.7 The authors concluded that “logistic analysis yielded hypotheses for colon cancer risk in males with potentially high exposure to solvents, abrasives and fuel oil and in those in jobs with . . . high stress”.7 A study by Courtney et al, involving 569 cases and 510 controls, revealed a strong association between a history of work-related problems and colorectal cancer.8 The odds ratio was 5.5 (95% CI, 2.3–23.5). The authors, explaining the wide confidence interval, stated that “because most of the events were relatively uncommon in this population, the estimates of effect were not precise”.8 Courtney et al subsequently reported another case–control study involving 774 pairs, again examining the relationship of job stress and risk for colon cancer.9 Participants in the highest-stress group had a slightly increased risk when compared with those in the lowest-stress group (odds ratio, 1.3; 95% CI, 1.0–1.6), but there was no evidence of a trend. The authors concluded that “if job stress, as reflected by perceived job demand or control, is a determinant of colon cancer, it is probably not a strong one”.9 The applicant for compensation (the prison officer’s widow) also relied on a study by Kune et al of 715 patients with colorectal cancer and 727 controls (data from the Melbourne Colorectal Cancer Study).10 Work problems were found to be significantly more common for colorectal cancer patients. Although recall bias was not completely controlled for, it was thought that it was “probably not an important factor”.10 Other articles by Kune et al were not cited by the applicant or by the prison officer’s employer (the respondent).11,12 One of these papers used data from the Melbourne Colorectal Cancer Study to evaluate the effect of personality on risk of colorectal cancer in 637 individuals with colorectal cancer and 714 controls. Questions that tested a particular personality profile with regard to cancer risk revealed a significant association between a particular personality type and risk of colorectal cancer. With the caveat that the results should be cautiously interpreted, Kune et al concluded that the data were consistent with the hypothesis that “personality type may play a role in the clinical expression of colorectal cancer”.11 Yet further data from the same study revealed that significant protection against colorectal cancer was associated with self-reported “religiousness”.12 How these findings might have affected the Tribunal’s decision is unknown. This selective use of data is a feature of the adversarial system in which “parties are not obliged to call all the relevant evidence . . . only that which favours their case”.2 Indeed, our review here may be similarly criticised for presenting further selective references. Although a comprehensive review of the factors that contribute to the occurrence and effective management of workplace stress exists,13 an objective and complete review of the medical literature with regard to stress and colorectal cancer has yet to be published. Other literature before the Tribunal included a review of evidence concerning any relationship between the mind and cancer.14 This review noted that “there is very limited evidence that either stress or depression are risk factors for the onset of cancer”. It concluded that: On balance, the findings suggest that some psychological factors probably do exert an influence on the onset and cause of cancer, but the extent of their influence is unknown. Clearly further research and replication studies are needed to clarify the nature of this relationship.14 Legal proofSamuels, writing in the Journal in 1998, provided a detailed outline of the differences between medical truth and legal proof. Commenting that the question to be answered in our adversarial legal system is not “What is the truth of the matter?”, Samuels conceded that “medicine is a science and law is not”.2 Causation in science has multiple defined criteria (such as strength and consistency of association, temporal association, specificity, dose–response relationship, known or theoretical mechanism and coherence of evidence).15 Causation in law has a different basis, being “determined as a matter of common sense”, so that an inference of causation in a legal sense may be drawn when the level of evidence may be insufficient for causation according to the scientific criteria described above.16 A medical fact is “one which can be empirically supported”, whereas a legal fact “is one which is more probable than other countervailing facts”.2 It appears from the Tribunal’s reasons for its decision that, whereas the respondent’s medical expert tried to use a scientific standard of proof in examining the evidence for a contribution of stress in cancer, the Tribunal was only concerned with the balance of probabilities. ConclusionTo date, the association between stress at work and colorectal cancer has been the subject of a limited number of conflicting and inconclusive studies. The decision made by the Tribunal turned on the medical and other evidence actually placed before it by the parties. In finding that on the balance of probabilities the prison officer’s employment contributed to his cancer, the Tribunal found it unnecessary to distinguish between causation and acceleration. Thus, the fundamental causation issue has not been subject to legal precedent. It will be of considerable interest to consider any further cases in which the question might again arise, especially in light of the then current state of relevant scientific evidence.

Allan D Spigelman FRACS, FRCS, MD · Peter Dwyer MSc(Soc), DipLaw, FACLM(Hon)

There are important distinctions to be made between the inquisitorial process of a tribunal, such as the South Australian Workers Compensation Tribunal, and the adversarial process of the courts. To quote the renowned English Law Lord, Lord Devlin: In the [adversarial process], the judge presides at the trial, directs the proceedings and rules on the law; he is not there to hold an inquiry. It is quite different from the [inquisitorial process] where witnesses are summoned by the court and examined by the judges, the role of counsel being to tender a witness, and ask supplementary questions.1 A tribunal is inquisitorial. It can ask its own questions of the witnesses called, and may have the capacity to commission its own expert advice and call its own witnesses. Often a tribunal has several people sitting on it; one is usually legally qualified, but others may be experts from the field that is the basis of the proceedings. Whereas claims for compensation for personal injuries arising out of a defendant’s negligence are brought in civil courts and determined by common law processes, in Australia the most common areas of injury — work- and transport-related accidents — are covered by “statutory” schemes. These are arrangements by which claims for compensation are assessed under specific legislation, rather than at common law. Many statutory workers’ compensation schemes were not established simply as narrowly defined insurance schemes, but were given flexibility to provide social benefits. For example, Lord Campbell’s Act,2 enacted in England in 1846, was intended to overthrow the ruling made under common law in 18083 that damages for the death of a human being could not be claimed by another person. The Act was passed to protect the widows and orphans of men killed in industrial accidents by providing, through statute, access to compensation for loss of the income of a bread winner — compensation that could not be obtained at common law. Many people would think that Mrs Simpson, the applicant in the case described by Spigelman,4 had a right to bring her claim for compensation for her husband’s death. That right does not exist at common law, but is provided by statute. In the courts, the claimant (civil) or the Crown (criminal) has the burden to prove its case, and the benefit of the doubt falls to the defendant. The major difference in the meaning of “doubt” between the criminal and civil courts is that, in a criminal court, the test is “beyond reasonable doubt”, a much tougher test than the civil court’s “on the balance of probabilities”. Simpson v South Australia (Department of Correctional Services) was heard in the South Australian Workers Compensation Tribunal, but the test was still “on the balance of probabilities”. The claimant in the Simpson case introduced medical evidence that it was a “common observation” (acknowledged not to be a proven scientific fact) that there was a link between stress and cancer. In most workers’ compensation schemes, compensation will be paid if work caused, aggravated or accelerated the injury — that is, either caused or was a “significant contributing factor” to the injury. The phrase “significant contributing factor” appears in much workers’ compensation legislation. It was defined in the Victorian County Court5 as meaning a factor whose contribution was “more than de minimis but less than a major or dominant factor”. Not a very high hurdle to jump! Paragraph 70 of Judge McCusker’s decision in the Simpson case underscores the test he applied: A careful examination of the material available in this case indicates, on the balance of probabilities [my emphasis], that the worker’s employment contributed to the cancer that caused his death. Doctors are often dismayed at the difference between the standard of proof required in civil cases (the balance of probabilities) and the medical/scientific standard. Many have the perception that judges (and tribunals) award compensation to claimants seen as needy — redistributive justice, in which money is taken from rich defendants (more specifically, their insurers) and given to the unfortunate. Therefore, many doctors would be dismayed at the Simpson judgment. Most would believe that any relationship between stress and cancer is at best tenuous, and certainly not proven to the standard required of science. They are also incensed when judges make decisions in intensely technical areas of medicine, saying that judges are no more qualified to decide purely medical issues than doctors are to decide legal issues. Most Australian states now adopt a different approach to resolving medical disputes raised in workers’ compensation claims. In South Australia, the medical issue was determined by the tribunal. In Victoria, Queensland and Western Australia, such disputes are resolved by referral to a multi-doctor medical panel or medical tribunal. Doctors are appointed to any one panel on the basis of the nature of the injury. For example, impairment arising from a back injury might be assessed by a panel consisting of an orthopaedic surgeon, a neurosurgeon, a psychiatrist and an occupational health physician. If the Simpson claim had been referred to a medical panel, the panel would probably have comprised a colorectal surgeon, a gastroenterologist, an oncologist and an immunologist, or similar, with acknowledged expertise in the area. These doctors would have used their existing knowledge, and would have viewed the expert opinions provided by the parties, critically analysed them, and checked the references cited, before forming a collective view. In contrast, the adversarial process encourages the use of medical “gladiators”, who are selected because their opinion advances the client’s cause. Multiple opinions, for and against, are put into evidence. This leaves judges (or juries) in the position of having to decide between competing schools of medical or scientific opinion. The most famous Australian example of the difficulty lay juries (and judges) experience when assessing expert evidence is the handling of the forensic evidence in Lindy Chamberlain’s trial for the murder of her baby, Azaria. The trial, held in the Supreme Court of the Northern Territory, resulted in Mrs Chamberlain being wrongly convicted of murder in 1982. Much of Judge McCusker’s judgment in the Simpson case is a critical analysis — by a lawyer (ie, the judge) — of the many medical opinions put into evidence by both the claimant and the defendant, leading to a final decision as to whose opinions he preferred. An inquisitorial medical tribunal approach encourages individual doctors to act genuinely as independent medical experts (removing any perceived taint as medical “guns for hire”, or, as it has been quaintly put, “rent-a-quacks”), and the final opinion is developed on a multidisciplinary collegiate basis. Opinions of the Victorian Medical Panels, the Western Australian Medical Assessment Panels and the Queensland Medical Assessment Tribunals are, by statute, final and binding. For example, section 68(4) of Victoria’s Accident Compensation Act 1985 states: The opinion of a Medical Panel on a medical question referred to the Medical Panel is to be adopted and applied by any court, body or person and must be accepted as final and conclusive by any court, body or person irrespective of who referred the medical question to the Medical Panel or when the medical question was referred. If South Australia had such a system, a panel of medical experts would have assessed Mr Simpson’s medical records and the expert evidence submitted both in support and rebuttal of the claim, made its own investigation of the literature, and come to an informed medical view. The panel would have had access to advice regarding the legal tests required by the appropriate statute. Whether the panel would have reached the same view as the judge cannot be said. But at least the medical basis for the claim would have been seen to have been thoroughly reviewed by truly independent medical experts — and a medical decision (subject to the law) made on a medical issue.

Paul Nisselle AM, MB BS, FRACGP

Thyroid nodules are common clinically (prevalence, about 5%) and even more common on ultrasound examination (about 25%). About 5% of thyroid nodules are malignant. Most thyroid cancers are well-differentiated papillary or follicular tumours with an excellent prognosis (10-year survival, 80%–95%). The incidence of papillary thyroid cancer appears to be increasing on the east coast of Australia. Fine-needle aspiration biopsy of the thyroid is the most cost-effective diagnostic tool. Recommended initial management of all follicular carcinomas and of papillary carcinomas > 1.0 cm is total thyroidectomy followed by radioiodine ablation. Most patients should be managed postoperatively with doses of thyroid hormone sufficient to suppress plasma levels of thyroid-stimulating hormone. Recurrences can occur many years after initial therapy, and follow-up should be lifelong.

Emily J Mackenzie MB BS · Robin H Mortimer FRACP, FACP

Clinical records Patient 1 A 77-year-old woman was referred to us for an urgent surgical opinion regarding an abdominal mass. Fifteen months previously, she had been referred to a major metropolitan hospital with symptomatic iron deficiency anaemia, and weight loss of 5 kg in 6 months. Gastroscopy, colonoscopy and abdominal CT scan were unremarkable. There were no clinical features to suggest malabsorption, nutritional deficiency or inflammatory bowel disease. A diagnosis of angiodysplasia was considered, although there was no direct evidence of this. The patient received a 5-unit blood transfusion and iron supplements. During the 7 months after initial presentation, she was seen in medical outpatient clinics six times. Over the next 8 months, she was admitted six times, transfused 13 units of red cells, and given two iron infusions. A labelled red cell scan showed no gastrointestinal bleeding. An abdominal ultrasound was unremarkable. Results of investigations for coeliac disease and pernicious anaemia were normal. A bone marrow biopsy was consistent with iron deficiency anaemia. On one occasion, the admitting registrar considered a small bowel follow-through, but this was not performed. Paroxysmal nocturnal haemoglobinuria was excluded. During the last of these admissions, a firm abdominal mass was palpated. A computed tomography (CT) scan revealed an 8 cm heterogeneously enhancing soft tissue mass in the proximal jejunum. Lymphoma was considered the most likely diagnosis, and the patient was referred to our department. Push enteroscopy revealed an ulcerated adenocarcinoma in the proximal jejunum (A). A 10 cm, poorly differentiated jejunal adenocarcinoma was resected. Eleven months after surgery, the patient has shown no further symptoms of anaemia, and no evidence of recurrence. Patient 2 A 68-year-old man was admitted to our department for laparotomy for a small bowel tumour. The patient had a past history of an open cholecystectomy. Twenty-eight months before admission, he had been referred to a gastroenterologist with symptoms of gastro-oesophageal reflux disease; he underwent gastroscopy, which showed reflux oesophagitis, and was treated with proton pump inhibitors. Eleven months later, he was referred to a gastroenterologist again with persistent symptoms. He was seen several times in the next 9 months, and was then admitted to a general surgical service of a metropolitan hospital with abdominal pain. A provisional diagnosis of small bowel obstruction was made, and the patient was discharged the following day once his pain had settled. Twice during the next 5 months, he presented to the emergency department with abdominal pain, nausea and vomiting. His symptoms settled with analgesia and fluids. Persistent retrosternal pain had not been helped by a variety of H2 antagonists, proton pump inhibitors or prokinetic agents. He was admitted to our surgical service after presenting on two successive days with severe epigastric pain. Upper gastrointestinal endoscopy showed severe reflux oesophagitis. The first and second parts of the duodenum were normal. Abdominal CT showed a circumferential mass in the proximal jejunum with dilation of proximal bowel (B). Small bowel follow-through then showed an annular, stenosing lesion in the region of the duodenojejunal flexure. At laparotomy, a localised adenocarcinoma was resected (C). The patient had adjuvant chemotherapy and 12 months after surgery was asymptomatic, taking no medication, and had no evidence of recurrence. A: Small bowel carcinoma detected on push enteroscopy (Patient 1). B: Abdominal CT scan showing a large dilated small bowel loop in the left upper quadrant (Patient 2). C: Operative specimen showing a localised, constricting cancer (Patient 2). Small bowel carcinoma is rare compared with gastric and colorectal cancer. Fifty-eight cases were reported in Victoria in 2001.1 Although the small bowel comprises 75% of the gastrointestinal tract length, less than 2% of gastrointestinal malignancies arise there.2-6 Adenocarcinoma accounts for 40% of small bowel malignancies; others include carcinoids, lymphomas and gastrointestinal stromal tumours, as well as metastases from melanoma, breast, lung and renal cancer.3,5,6 Small bowel tumours are rarely considered as a differential diagnosis, and their discovery is usually greeted with surprise. They are much more common in patients with coeliac disease (risk of lymphoma) and in hereditary bowel cancer syndromes (hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, and Peutz–Jegher syndrome).2,4,6 Thus, small bowel tumours must be considered in patients with a family history of bowel cancer. A low index of suspicion for small bowel tumours is a result of their relative rarity, but delayed diagnosis may reduce the chance of successful treatment. Reasons for diagnostic delay include the non-specific presentation, the lack of awareness of the diagnosis and the inaccessibility of the small bowel to investigation. In one analysis of 77 consecutive patients with primary small bowel malignancy over 22 years, average delays were 2 months before presentation to primary care physicians, 8 months from presentation until appropriate investigation, and 12 months from presentation until definitive diagnosis.7 Our first patient represents a common scenario. A patient with iron deficiency anaemia had investigations to exclude gastroduodenal, colonic, and extra-intestinal sources of blood loss. The inaccessibility of the small bowel to investigation resulted in a 15-month delay to diagnosis of a small bowel adenocarcinoma. An abdominal computed tomography (CT) scan performed early in the investigation of anaemia failed to show any disease, and the patient’s symptoms were attributed to intestinal angiodysplasia, a diagnosis that is difficult to confirm. The failure to perform small bowel follow-through, despite its low sensitivity, may have contributed to the delay in diagnosis. Our second patient highlights the non-specific way in which small bowel adenocarcinoma can present. The patient presented with symptoms of reflux oesophagitis refractory to treatment. The abdominal CT scan was the pivotal investigation that alerted clinicians to a lesion in the jejunum. CT is frequently used to assess the abdominal cavity. The accuracy of abdominal CT in detecting primary small bowel tumours is poor — reported as 57% in one study of 85 patients.5 It is a useful staging procedure, but, given the poor sensitivity for small bowel pathology, abdominal CT should be used in concert with other imaging modalities. Barium contrast studies are the standard test for intraluminal or mucosal abnormalities beyond the duodenojejunal flexure, but have limited sensitivity.3-5 Small bowel enteroclysis is more sensitive than small bowel follow-through,8 and involves delivery of barium to the small bowel via an intestinal tube. Push enteroscopy, using a paediatric colonoscope, is an alternative, but does not visualise the entire small bowel. Video capsule endoscopy has shown promise in the diagnosis of small bowel disorders.9,10 It is not yet widely available, and further trials are required before its role is defined. It is contraindicated when small bowel strictures are suspected, so should be preceded by small bowel follow-through in these cases.9,10 Early studies show that it is more accurate than small bowel follow-through,9,10 so, when there is a strong clinical suspicion of small bowel pathology, patients should be referred to a specialist centre. Occasionally, exploratory surgery is appropriate, particularly when anaemia and abdominal pain coexist and the results of all other investigations have been negative. ConclusionThis report highlights the difficulties in diagnosing small bowel tumours. The diagnosis requires a high index of suspicion and early investigation. Iron deficiency anaemia in an older patient with normal results of endoscopic studies is not an uncommon clinical scenario. Small bowel malignancy should be considered when more common causes have been excluded, especially if there are general features suggestive of malignancy, such as anorexia, abdominal pain or weight loss. Abdominal CT scan coupled with small bowel follow-through is the minimum requirement. If this is negative, further investigation in a specialist centre should be considered. Lessons from practice Small bowel malignancy should be considered in cases of unexplained gastrointestinal bleeding, anaemia or obscure abdominal symptoms. Abdominal computed tomography scan and small bowel barium studies are minimum requirements for investigation, but have limited sensitivity. Capsule enteroscopy appears to be more accurate than barium studies and may have an increasing role in these cases as it becomes available.

Ronil V Chandra MB BS · Julie A Miller MD, FRACS · Ian T Jones MB BS, FRACS · Brett Manley MB BS · G Bruce Mann MB BS, PhD, FRACS

Adolescents and young adults fare worse than children, yet do not have the same access to clinical trial therapy In almost half a century of clinical trials in children with cancer, survival rates have increased from less than 20% to over 80%. The national and international cooperation for such results has been an enormous feat of organisation. However, older adolescents and young adults, while having a higher and increasing incidence of cancer, have not fared so well.1 As shown by Mitchell and colleagues in this issue of the Journal (page 59), few are recruited into clinical trials, and improvement in survival has lagged behind that in younger patients.2 Some cancers that affect adolescents have a good prognosis (eg, Hodgkin’s disease and gonadal tumours), and little difference in survival is seen between patients who are treated in trials and those who are not. Yet clinical trials are still necessary to find the least toxic therapy while maintaining excellent survival. On the other hand, other cancers common in adolescents, such as acute myeloid leukaemia, acute lymphoblastic leukaemia, rhabdomyosarcoma, osteogenic sarcoma and Ewing’s sarcoma, are associated with considerably lower 5-year disease-free survival rates in adolescents than in younger patients.3 With increasing intensity of therapy, the importance of supportive care and a multidisciplinary approach cannot be over-emphasised. Outcomes of adolescents with acute lymphoblastic leukaemia have been reported to be markedly better with paediatric-based, high-risk (intensive) therapy performed in large teaching hospitals with appropriate support and a commitment to multidisciplinary coordinated care. In Children’s Cancer Group trials between 1989 and 1995, older adolescents had a 6-year event-free survival of 64%, compared with 38% for similar patients on (adult) Cancer and Leukemia Group B trials.4 Cooperation between paediatric and adult groups is essential to encourage entry into clinical trials. In France in 1993 and 1994, 15–20-year-old patients with acute lymphoblastic leukaemia treated within the paediatric FRALLE-93 study had a 5-year event-free survival of 67%, compared with 41% for 15–20-year-olds treated within the adult LALA-94 study.5 How can the lessons learnt in the large, multi-institutional, national and international paediatric cooperative groups be translated into better outcomes for adolescents and young adults with cancer? The Children’s Oncology Group (United States, Canada, Australia, New Zealand) and adult cooperative groups sponsored by the National Cancer Institute have identified four initiatives to improve the accrual of adolescents and young adults with cancer into clinical trials:2 Improving access to care through understanding barriers to participation. These barriers remain largely unstudied, but might include the time, cost and effort of being involved in a clinical trial, which may deter both physician and patient. Oncologists in private practice may retain these patients rather than referring them to a tertiary-care facility or cooperative group member institution. Also, clinicians and patients may not be aware of opportunities for clinical trials, the age policies of hospitals may prevent access to clinical trials for eligible patients, eligibility criteria may exclude some adolescent and adult patients, or there may be no available clinical trial for a patient. Developing a cancer resource network to provide information about clinical trials to patients, families, healthcare professionals and the public. Enhancing adherence to protocol therapy among adolescents. Although compliance was not found to be poor in the study by Mitchell et al,1 adolescent and young adult patients are often perceived as having difficulty in complying with treatment while keeping up their normal lives. Ancillary medical, psychological and educational support should be directed towards their specific needs.6 Increasing adolescent and adult participation in sarcoma trials specifically designed for patients in this age group. Just as paediatric oncologists have little experience with epithelial tumours, some adult oncologists have limited experience managing rare sarcomas.7 Cooperation between paediatric and adult groups is essential to encourage entry into clinical trials. For example, many Children’s Oncology Group trials will admit patients up to 30 years of age. It is imperative that alliances are formed to enable haematologists and oncologists who treat adults to enrol their younger patients in these trials. Although institutions that are members of the Children’s Oncology Group undergo rigorous performance monitoring to maintain high quality of care and data, this should not be a hindrance to such associations. Managing cancer patients in clinical trials requires significant financial support for administration and data management, but the benefit in improved survival will prove to be highly cost effective. Current funding models for research in Australia may not be suitable for the funding of clinical research such as cancer trials. National Health and Medical Research Council funding is tied strongly to researchers’ previously published research. Clinical research as part of a large cooperative group will not lead to numerous publications for individual clinicians. Nevertheless, commitment to such trials must be acknowledged by funding groups so that appropriate financial support to treat patients in trials is forthcoming. Only in this way will Australians of all ages with cancer have the benefit of the best evidence-based treatment within randomised controlled clinical trials in centres of excellence.

Catherine H Cole FRACP, FRCPA

Radiotherapy should be an integral part of a comprehensive national cancer control plan In June 2002, the Radiation Oncology Inquiry (ROI), chaired by Peter Baume, delivered its report, A vision for radiotherapy.1 The inquiry was, some might say, a cynical attempt by the then Federal Minister for Health and Ageing to defuse the furore created by a series of questions-without-notice by the Federal Opposition. The questions arose from the 2001 National radiation oncology strategic plan of the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists (RANZCR).2 However, the strategic plan disclosed nothing that should have taken the Government by surprise. Over the past two decades, nearly 50 reports have delivered the same messages: that radiotherapy is a vital part of cancer treatment, that radiotherapy services have been chronically under-resourced, that this deficiency has been deteriorating rapidly, and that correction of the lack of resources and manpower is long overdue. In this article we review the progress over the past year, since the release of the ROI report. What, then, are the problems? There is strong evidence that about 50% of all patients with cancer should receive radiotherapy at some stage during their illness.3 Using that benchmark, a survey for the abovementioned strategic plan estimated that each year in Australia about 10 000 patients who might have benefited from radiotherapy did not receive it. The survey also revealed a catalogue of insufficient and antiquated treatment facilities and an inadequate supply of radiation oncologists, radiation therapists and medical physicists — the three professions that are central to radiation oncology. For example, in New South Wales alone, a third of the linear accelerators in public radiotherapy departments were closed because of a lack of radiation therapists, and the effects of closure were reflected in long waiting times for radiotherapy. In a report on 25 000 patients treated between 1999 and 2001,4 the Australian Council on Healthcare Standards found that, over that period, the proportion of patients who waited more than 21 days for treatment had doubled. A recent survey by the RANZCR Faculty of Radiation Oncology confirms that long waiting times persist.5 Delay in receiving radiotherapy results in higher cancer recurrence rates and lower survival rates.6,7 Underlying the problems in service delivery, the ROI noted, Radiation therapy has suffered most seriously from the fragmentation of responsibilities between different organisations and governments. In itself, this is not unusual in the health care industry, but its effect has also been serious, as this fragmentation of responsibilities is to blame for the lack of action in the past 20 years — even though all parties are in general agreement about what problems need to be addressed. (p 14) The ROI made 96 recommendations, of which the five key action items are summarised in Box 1. In response, the Australian Health Ministers’ Advisory Council established a Radiation Oncology Jurisdictional Implementation Group (ROJIG), with representatives of each state and territory government, in an attempt to get all jurisdictions together at the same table. Paradoxically, the professions are not directly represented in ROJIG. The group has met several times during 2003 and established subcommittees to address issues of patient access, workforce, funding and quality. Although these subcommittees have some professional representatives, committee members have to sign stringent confidentiality agreements, resulting in the perception that the professions are not adequately consulted. ROJIG reported to the Health Ministers in November 2003,8 and has already endorsed, accepted and completed 35 of the 96 ROI recommendations. A further 50 recommendations were endorsed. Due in large part to the representations of consumer groups as well as the professions, the need to improve radiotherapy services has become a political priority. At the time of the 2001 federal election, the Australian Government committed $72.7 million to improve regional access to radiotherapy, including the funding of new facilities.9 In 2002, the Victorian Government pledged $78 million to build a new radiotherapy department at the Latrobe Regional Hospital in Gippsland, expand facilities at Geelong and Moorabbin hospitals, and replace old linear accelerators at existing metropolitan facilities. The Australian Government is also contributing $12 million to these projects.10 In 2003, the New South Wales Government budgeted $85.2 million to build new facilities, replace old equipment and improve training in radiation therapy and physics.11 Projects under way to improve radiotherapy services in various states are summarised in Box 2. Because of the long lead times involved, no new facilities have been brought into service since the ROI report was released. Long waiting times persist and are worsening in many centres. In the private sector, which treats more than a third of all patients, patient out-of-pocket costs are escalating, because outdated Medicare Benefits Schedule rebates fall far short of the cost of delivering quality radiotherapy. Although increased government investment in capital equipment is now taking place in the public sector, operational funding constraints continue to limit the ability of departments to meet service requirements. To us the solutions are clear. Workforce planning is required both in the short and long term. The recent initiatives, while laudable, were a stopgap response rather than a step towards building a rational framework for expanding the workforce. Working the staff harder and longer is not cost-effective12 and leads to higher staff resignation rates.13 Radiotherapy needs a sustainable funding model that supports the real cost of quality radiotherapy and a strong, profession-led quality improvement program to ensure that quality is achieved. The outstanding problem for radiotherapy and, indeed, all cancer services in Australia is that there is no nationally coordinated cancer care policy. Australia needs to develop and implement a comprehensive cancer control plan that incorporates radiotherapy in the overall context of cancer management. Fortunately, there are signs that things may be changing. The Australian Government has embarked on developing a National Service Improvement Framework for cancer, driven by the National Cancer Control Initiative’s report, Optimising cancer care in Australia.14 Victoria has just completed a framework for cancer services,15 and New South Wales has published a framework16 and established a Cancer Institute with the task of developing a cancer control plan by June 2004. Western Australia and Queensland have also started to develop cancer plans. Cancer is a complex disease that requires a diverse range of specialist and generalist treatment services. There is no single government agency responsible or accountable for the outcomes of cancer management in Australia. Without an accountable nation-wide approach, the ROI report will become just another in the series of mirages that have promised, but not delivered, the access to quality care that Australians with cancer require and should expect. 1: Major recommendations of the Radiation Oncology Inquiry1 Establish an independent national body to oversee radiotherapy, reporting to the Ministers for Health, to address the fragmentation of healthcare delivery. The national body would be responsible for quality and productivity issues, such as facility accreditation, clinical protocols, benchmarking and coordinating data collection. Improve the availability of radiotherapy in rural and regional Australia. Ensure adequate workforce, especially in radiation therapy and medical physics. Ensure appropriate quality of services by accrediting facilities and having mandatory continuing professional development. Resolve the disputes over who should be paying for radiotherapy, and tensions between public and private providers, by pooling state, territory and Commonwealth funding. 2: Projects under way, in various government jurisdictions, to improve radiotherapy services in Australia Federal Increasing the number of undergraduate radiation therapy students by 50% Helping establish a national uniform training program in medical physics Introducing a postgraduate radiation therapy course at Monash University (VIC) Providing partial funding to replace outdated linear accelerators in all jurisdictions Funding a new radiotherapy centre in Toowoomba (QLD) Funding a skills mix and work analysis project New South Wales Employing more radiotherapy tutors Employing physics registrars for the first time in Australia Building new radiotherapy departments at hospitals in Port Macquarie and Coffs Harbour Victoria Building a new radiotherapy department at Latrobe Regional Hospital Providing a new linear accelerator at Moorabbin Hospital Replacing outdated linear accelerators at all public facilities Establishing a Ministerial Taskforce for Cancer South Australia Replacing three linear accelerators Western Australia Providing two new linear accelerators for hospitals in Perth Appointing a Chief Cancer Officer Northern Territory Conducting a feasibility study of local radiotherapy services

Michael B Barton MB BS, FRANZCR · Lester J Peters AM, MD, FRANZCR · Lizbeth M Kenny MB BS, FRANZCR

Objectives: To describe the location of treatment, recruitment to clinical trials and outcomes for adolescents and young adults treated for cancer in Victoria.Design and setting: Retrospective review of all adolescents and young adults aged 10–24 years diagnosed with cancer between 1992 and 1996, identified from the Victorian Cancer Registry.Main outcome measures: Treatment regimen (clinical trial, treatment protocol or neither), compliance with treatment and 5-year survival.Results: Questionnaires were completed for 576 of 665 eligible adolescents and young adults (87% response rate). Recruitment into clinical trials decreased with increasing age. Adolescents aged 10–19 years were more likely to be recruited to a clinical trial if treated at a paediatric hospital. For all cancers, 5-year survival was similar across the age groups and was not influenced by the place of treatment. Only 1% of adolescents and young adults failed to complete planned therapy due to non-compliance.Conclusions: Despite a similar incidence of cancer to that in younger children, adolescents and young adults with cancer are poorly recruited into clinical trials in Victoria. Establishment of a cancer resource network in Victoria may provide information to both paediatric and adult oncologists about currently available clinical trials.

Anne E Mitchell MB ChB, FRACP · Deborah L Scarcella BSc, GradDip · Gemma L Rigutto BSc, GradDip · David M Ashley PhD, FRACP · Vicky J Thursfield BSc, GradDip · Graham G Giles MSc, PhD · Maree Sexton MB BS, FRANZCR

Objective: To establish the prevalence and predictors of skin screening by general practitioners in regional Queensland.Design: Questionnaire administered to participants by professional interviewers via telephone.Participants and setting: Participants were 3100 adults aged ≥ 30 years (66.9% overall response rate), selected from residents of 18 regional Queensland communities with populations of between 2000 and 10 000 (as recorded in the 1996 Australian census). Within the last 10 communities surveyed, an additional telephone survey of 727 participants evaluated mole density. The survey was conducted between January and October 1998.Main outcome measure: Prevalence of whole-body skin examinations by GPs.Results: 11% of participants reported a whole-body skin examination by a GP during the previous 12 months, and 20% during the previous 3 years. Men and women reported a similar prevalence of whole-body skin examinations. Factors associated with a significantly increased likelihood of having had a whole-body skin examination within the previous 3 years included a positive attitude towards skin screening, a personal history of non-melanoma skin cancer, a tendency to burn, and having more than four moles on the right upper arm.Conclusions: A substantial proportion of Queenslanders undergo skin screening. Those at highest risk for skin cancer are more likely to be screened.

Monika Janda PhD · Philippa H Youl MPH · Joanne F Aitken PhD · Mark Elwood MD · Ian T Ring FAFPHM · David W Firman MMath · John B Lowe DrPH

Objective: To assess the importance of cancer “breakthroughs” reported in the popular media 10 years after their publication.Study design: Questionnaire-based survey in 2003 of expert opinion on the importance of all alleged cancer “breakthroughs” in cancer research or treatment reported in news articles in The Sydney Morning Herald between 1992 and 1994.Main outcome measures: Assessment of each “breakthrough” by an expert in the relevant cancer subspecialty on seven measures of current importance.Results: 31 unique reports of alleged cancer “breakthroughs” were identified, and experts responded to questionnaires on 30. Thirteen of these 30 reports (43%) were judged as not having been supported by further research in the following decade, with three (10%) having been refuted, while 16 (53%) were judged to remain potential breakthroughs, but more research was required. Eight “breakthroughs” (27%) had, or would soon be, incorporated into practice.Conclusion: Cancer research findings reported in newspapers as “breakthroughs” are often not true breakthroughs but may be important for ongoing research. Consumers are likely to be receiving an overly optimistic picture of progress in understanding and treating cancer.

Ethel S Ooi MB BS · Simon Chapman PhD

For women with early breast cancer, multidisciplinary care has the potential to reduce mortality, improve quality of life and reduce healthcare costs. In Australia, the diversity of healthcare delivery settings and types of care means that a single model of multidisciplinary care may not be appropriate. The “Principles of multidisciplinary care” were developed to provide a flexible framework for the provision of multidisciplinary care in Australia. The Principles emphasise five key elements: the team, communication, access to the full range of therapies, standards of care and involvement of the woman. This flexible, principle-based approach to multidisciplinary care is unique. The Principles have the potential to be applied to other cancers and other chronic diseases.

Helen Zorbas MB BS · Kathy Rainbird PhD · Karen Luxford PhD · Bruce Barraclough FRACS · Sally Redman PhD

Rosie G Scott,* John T Edwards,† Richard M Mendelson,‡ Geoffrey M Forbes§ * Research Fellow, ‡ Radiologist, Department of Diagnostic and Interventional Radiology; † Gastroenterologist, § Gastroenterologist (corresponding author), Department of Gastroenterology and Hepatology; Royal Perth Hospital, PO Box X2213 GPO, Perth, WA 6000 geoff.forbesAThealth.wa.gov.au To the Editor: The burden of colorectal cancer can be minimised, firstly, by early and appropriate investigation of symptoms; secondly, by screening those at higher-than-average risk without symptoms; and thirdly, by community-based screening of asymptomatic people aged over 50 years who are at average risk. Major screening programs using faecal-occult-blood testing (FOBT)1-3 or flexible sigmoidoscopy4 have not necessarily made this differentiation. These tests lack the sensitivity of colonoscopy, which is generally indicated for those with symptoms or a strong family history of colorectal cancer. In our recent community-based screening program in which we used virtual colonoscopy, we excluded those at higher than average risk for colon cancer (that is, they were symptomatic or had at least one first-degree relative with colon cancer), as our standard of care for these patients is colonoscopy. They were given verbal and written advice to see their general practitioner, with the expectation that most should have colonoscopy. They were followed up an average of 12 months (range, 6–15 months) later, by letter and telephone, to determine the outcome of this advice. Of 2000 participants aged 50–69 years who were offered screening, 90 (4.5%) described having symptoms or a first-degree relative with bowel cancer, but had not undergone investigation. Follow-up information obtained from 71 of these people indicated that 21 had a relevant family history and 50 described recent bowel symptoms. Only 35 (49%) had discussed further investigations with their GPs — 19 (27%) had undergone colonoscopy, and five of these (26%) had advanced colorectal neoplasia (CRN). One had tubular adenoma (> 1 cm), one showed villous architecture, one had intramucosal carcinoma, and two had cancer. Four other participants had had negative results on other investigations. These were FOBT alone in three (two symptomatic, one with family history) and barium enema in one who had bleeding. Common reasons for not consulting their GPs were because of good health (15 participants), resolution of symptoms (12), and perceived lack of need for tests (10). These data have important implications for CRN screening programs, including recently commenced Australian pilot programs (www.cancerscreening.gov.au). Firstly, there is likely to be an improved yield of advanced CRN when a previously uninvestigated high-risk group is identified within a screening program. Secondly, people identified as having higher-than-average risk for CRN need special attention to ensure there is adherence to advice on appropriate follow-up. Thirdly, procedures are required to ensure colonoscopy is appropriately undertaken when participants do consult their GPs. Accordingly, rather than adopting an exclusion policy within a screening program based on FOBT or flexible sigmoidoscopy, we believe it is appropriate that people at greater risk for CRN are identified and offered colonoscopy within that program.

Rosie G Scott · John T Edwards · Richard M Mendelson · Geoffrey M Forbes

Given the controversy over this strategy, Australia should be involved in its evaluation Lung cancer is the leading cause of cancer death in Australia and has a dismal prognosis, with 7800 new cases and 6800 deaths each year, and a 5-year post-diagnosis survival of only 12%. New cases increasingly occur in ex-smokers.1 Helical computed tomography (CT) is a fast and sensitive screening technique that can detect early-stage lung tumours, potentially increasing the proportion of patients who can be offered curative treatment. Newer scanners can perform studies with lower radiation exposure. However, use of this technique is controversial; the studies suggest that it has benefits that are uncontrolled, with no concurrent or randomised comparison group. Proponents of helical CT screening argue that its high sensitivity and the early results of studies showing that it detects small, early stage and operable cancers demonstrate its clear benefits.2,3 In the Early Lung Cancer Action Project in the United States, 1000 asymptomatic smokers or former smokers aged over 60 were screened with low-dose helical CT and conventional chest x-rays; 23% had non-calcified pulmonary nodules detected by CT, while only 7% had abnormalities detected by chest x-ray. Of those with nodules on CT, 12% were eventually diagnosed with malignancy, of which 85% were stage I tumours.4,5 In contrast, only 20% of lung cancers in patients presenting in Victoria in 1995 were localised.6 Other similar uncontrolled studies in the United States, Japan, Germany and Finland showed that from 5%7 to over 50%8 of people screened have an abnormality detected. While many can be investigated with non-invasive tests and reassessment, the substantial rate of false-positive scans requiring potentially hazardous interventions is a real concern. Others argue that studies with no control group are open to severe biases and give misleading results.9,10 Non-randomised comparisons between screen-detected and conventionally diagnosed patients that assess outcomes such as tumour size and survival are open to selection, lead time, prevalence–duration and overdiagnosis bias, all of which tend to make the outcomes in the screened group appear more favourable.11 The experience with previous trials of screening for lung cancer, using chest x-ray and sputum cytology, shows these problems. A randomised trial in Czechoslovakia demonstrated that, in the screening group, 53% of tumours were at an early stage, 25% were operable, and 5-year survival was 23%, compared with figures of 21%, 16% and zero 5-year survival in the unscreened group.12 However, the death rate from lung cancer over the subsequent 15 years was actually higher in the screened group; this discrepancy arises from the biases noted above. A trial at the Mayo clinic in the United States showed similar results.13 A Cochrane meta-analysis of trials of lung cancer screening shows no difference in all-cause mortality (relative risk, 1.01; 95% CI, 0.94–1.08), and a higher mortality from lung cancer in the screened groups (relative risk, 1.11; 95% CI, 1.00–1.23).14 Randomised trials of helical CT screening have begun. The US National Lung Screening Trial started in 2002 and plans to recruit 50 000 high-risk subjects aged 55–74 over 2 years; in the first 6 months, 16 000 subjects have been recruited. The intervention group will be offered helical CT, and the comparison group will be offered conventional chest x-ray, each at baseline and annually for 2 years. Follow-up will continue to 2009.15,16 The trial will have power to detect a 20% reduction in mortality, and costs are estimated at US$200 million. Other smaller randomised trials are in progress. A trial with 40 000 participants has been planned in the United Kingdom, but funding has not been approved. Many non-randomised trials, most linked to the Early Lung Cancer Action Project, are in progress. In 2002, the National Cancer Control Initiative in Australia set up a working group and a wider advisory group to review the state of knowledge of helical CT screening and make recommendations about its future in Australia. Their report recommends that a coordinated analysis of Australian clinical experience with helical CT screening be undertaken, along with a study to determine the prevalence of benign nodules in Australia, which may differ from that in other countries.17 Cost–benefit studies are recommended, largely to assess what degree of mortality benefit would have to be shown by the randomised controlled trials to fulfil acceptable economic criteria for screening. The report concludes that an Australian-based randomised trial would be impractical and too expensive, but recommends that one or more Australian centres should be involved in the international randomised trials. Such involvement would need funding of around $1 million for 3–5 years; but would let us fully contribute to the essential evaluation of a challenging new approach to our leading cause of cancer deaths.

Mark Elwood MD, DSc · Donald A Campbell MD, FRACP · Margaret P De Campo FRACR, MPH

Vaccination has the potential to reduce the global burden of disease from genital HPV infection Cervical cancer is the third most common cancer worldwide and, for women, the second most common after breast cancer. Each year there are about 466 000 new cases globally, and around 232 000 women die of cervical cancer.1 Eighty per cent of cases occur in developing countries, where it is the leading cause of cancer-related death among women.1 Precursor lesions (high-grade dysplasias) precede the development of cancer by years. With appropriate screening programs and early diagnosis and treatment, this reproductive health problem becomes a preventable public health issue. However, data for the past 5 years indicate that only about 5% of women in developing countries are screened, compared with 40%–50% of women in developed countries. Further, because of the insensitivity of the Papanicolaou (Pap) test, even in countries with appropriate screening programs, 50% of adenocarcinomas and at least 25% of squamous cell carcinomas occur in adequately screened women. Association between human papillomavirus and cervical cancerMolecular biology has finally established the causal association between persistent infection with certain human papillomavirus (HPV) genotypes and cervical cancer, supporting previous observations relating cervical cancer to sexual activity.2-4 HPV genotypes 16 and 18 are now categorised as human carcinogens,2 and it is noteworthy that these two HPVs are present in over 70% of cases of cervical cancer worldwide.2-4 Further, in a study of almost 1000 cervical cancer cases worldwide, the prevalence of HPV infection was 99.7%.3 Recently, less prevalent oncogenic HPV genotypes (31, 33, 45, 52, 58, 59) have also been found to be strongly associated with cervical cancer, with odds ratios several hundredfold.4 With such high relative risks, the association between persistent oncogenic HPVs and cervical cancer is the strongest for any environmental factor and human cancer. From recently completed longitudinal studies, we now know that genital HPVs are the commonest sexually transmitted viral infection. They are largely transient, usually asymptomatic and most are of no clinical consequence. The mean duration of carriage is 4 months for low-risk oncogenic types and 8 months for high-risk oncogenic types, with HPV-16 carriage being even longer.5 Genital warts are caused by genotypes 6 and 11 (low-risk HPVs), while persistent infection with oncogenic genotypes (over years and in a minority of patients) results in severe dysplasia or, ultimately, carcinogenesis. This process involves other cofactors (host and/or exogenous factors, such as high parity, cigarette smoking) and complex pathways, which are not completely understood. HPV DNA as a marker for precursor lesionsPersistent infection with oncogenic HPVs precedes virtually all high-grade dysplasias or neoplasias. Thus, persistent positivity for high-risk HPV DNA is a marker for current or subsequent development of precursor lesions,5 with persistent HPV DNA type-specificity being an even stronger predictive factor.6 Cohort analyses show that negative baseline Pap and HPV DNA tests are associated with very low risks of high-grade disease (0.16%). By comparison, women with positive HPV DNA tests and abnormal Pap smear results have a 4.54% cumulative incidence of high-grade dysplasia or cancer.7 HPV DNA testing, with its higher sensitivity for detecting underlying high-grade lesions than the Pap test (and the advantage that it can be performed on self-collected samples), is being reviewed for its clinical utility, either in triage of inconclusive or minimally abnormal smears, in conjunction with the Pap test, or as a stand-alone test in primary screening.5 It may also have a role as a test of cure after ablation for cervical dysplasia; persistence of HPV DNA after treatment could be an accurate predictor of residual disease or relapse.5 Of note, in the United States, HPV DNA (Hybrid Capture 2) testing was recently approved for use with the Pap test for women 30 years and over.8 Vaccination prevention at last?The preliminary results of a recent trial of a monovalent HPV genotype 16 vaccine were received with great interest and enthusiasm (Box). The vaccine provided vaccinees with high-level protection for incident and persistent HPV-16 infection (as a surrogate for invasive cancer) and HPV-16-related cervical intraepithelial neoplasia (CIN).9 Now awaited are larger studies to prove that clinical disease is prevented by vaccination, and the results of current clinical trials evaluating multivalent vaccines (HPV types 6, 11, 16 and 18). If these vaccines are as successful as the interim monovalent vaccine,9 they have the potential to prevent genital warts and over 70% of dysplasias and cancers, as well as reduce the occurrence of abnormal Pap smear results and the costs of their follow-up and management. Pivotal in the development of these vaccines was the production of virus-like particles (VLPs) — an Australian first.10 The VLPs used for the HPV-16 vaccine are viral subunits, composed of the major capsid protein L1 or outer shell of HPVs. Being devoid of DNA, they are not infectious. In Phase 1 and 2 clinical trials, VLPs have been shown to be not only immunogenic and safe, but able to induce strong cell-mediated and humoral immune responses. Most encouraging is that VLPs produce neutralising antibodies in animal models that are protective against challenge as well as long lasting. We need to see whether VLPs induce similar long-lasting immunity in humans. Second-generation vaccinesSecond-generation vaccines will need to be easier and cheaper to develop, give a broader coverage, have a better delivery system, allow better mucosal delivery, and possibly incorporate both prophylactic and therapeutic cover. The initiatives of the Gates Foundation to reduce cervical cancer in developing countries, where the disease is most common, are to be commended.11 Initiatives to promote second-generation vaccines (eg, vaccines that are cheaper to manufacture and available in a non-injectable form) have been discussed at a meeting of HPV vaccine experts, convened by the Gates Foundation in Seattle, Washington, in September 2002. Therapeutic vaccines have been successful in animal models, and there have been various Phase I and II trials in humans using HPV subunits (modified fragments of the HPV E6 and E7 genes), as well as chimeric and DNA viral approaches.12 These trials have shown some encouraging results for intraepithelial neoplasias, although clinical trials are not as advanced as for the prophylactic vaccines. An important question for vaccine development is whether there will be any cross-protection between types (immunity induced by natural infection is type specific), or whether effective vaccine-induced immune responses to one common high-risk HPV might simply open the door to another, currently less common type. In Australia, mortality from cervical cancer has been reduced substantially by an effective Pap screening program, but this comes at a considerable cost, both to the health budget and to women who face the psychological impact of having an abnormal Pap smear result. Ultimately, successful vaccination has the greatest potential to reduce the global burden of disease from genital HPV infection. Development of a vaccine for a sexually transmitted infection, the infective agent of which can not be grown by traditional methods in the laboratory, could be seen as a very important breakthrough, particularly for Australia (as VLPs were developed here).10 An effective prophylactic vaccine could ultimately obviate the need for population-based Pap smears, while an effective therapeutic vaccine could provide a change to conventional management of cervical disease, including reducing the need for colposcopy. However, lowering the incidence of dysplasia and neoplasia will take many years. In the meantime, the various prevention strategies still need to be endorsed and maintained. Apart from cervical cancer, other anogenital cancers and some non-melanoma skin cancers are also attributed to oncogenic HPVs. A successful vaccine could ultimately have an even greater impact on HPV-related diseases. Other challengesBesides vaccine delivery, vaccine implementation would include educating the general public about HPV (public awareness and acceptance), de-stigmatising HPV infection, and gaining acceptance for vaccinating adolescents (or pre-adolescents), possibly of both sexes, for a sexually transmitted infection before their sexual début. For the future, we need a better understanding of the transmission dynamics of HPV. A public health policy will need to be guided by mathematical modelling of the impact of an HPV vaccine on Pap screening. This also applies to the interrelationship between HPV and abnormal Pap smear results, and any concomitant psychological impact on women faced with an abnormal result of an HPV DNA test or a Pap smear. A controlled trial of a human papillomavirus (HPV) type 16 vaccine, by Koutsky et al9 Study population: 2392 young women, 16–23 years old (no more than five male sexual partners during their lifetime). Intervention: Intramuscular vaccination with three doses of placebo or HPV-16 virus-like particle (VLP) vaccine (Day 0, Month 2, Month 6). Follow-up: Month 7, 12 and thereafter 6 monthly to 48 months (Pap test, and HPV DNA 16 and HPV-16 antibody assayed). Colposcopy biopsy tissue evaluated for cervical intraepithelial neoplasia (CIN). Primary endpoints: Persistent HPV-16 infection (the detection of HPV-16 DNA in samples obtained at two or more visits ≥ 4 months apart, in those HPV DNA negative at Day 0 and Month 7) and HPV-16-related CIN. Results: After a median follow-up of 17.4 months, the incidence of persistent HPV-16 infection was 3.8/100 woman-years (placebo group) and 0/100 woman-years (vaccine group) (100% efficacy; 95% CI, 90–100; P < 0.001). Nine cases of HPV-16-related CIN occurred, all in the placebo group. 99.7% of the women vaccinated seroconverted and with a robust antibody response. Conclusion: HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related CIN. The study is continuing.

Suzanne M Garland FRCPA, FACSHP, RANZCOG ad eund, MD

Achieving and maintaining a high rate of attendance for screening and two-yearly re-screening is essential for the success of the BreastScreen Australia program. A low participation rate will result in fewer breast cancer-related deaths being prevented. Results of two recent large randomised trials do not show that a systematic approach to breast self examination finds breast cancers early or impacts on survival. "Breast awareness" and the prompt reporting of breast symptoms are important early detection messages for women of all ages. General practitioners have a key role in the promotion and provision of information about effective public-health initiatives for the early detection of breast cancer.

Helen M Zorbas MB BS

Ovarian cancer is the leading cause of death from gynaecological malignancies. No precancerous lesions have been identified. Bimanual examination has not been proven to be of value as a screening test. Transvaginal ultrasound examination, with or without measurement of CA 125 levels, is currently being evaluated for population screening. Women at high risk of ovarian cancer should be screened annually — with measurement of CA 125 level and transvaginal ultrasound examination.

Cleola Anderiesz PhD · Michael A Quinn MGO, FRANZCOG, FRCOG

Routine screening for endometrial carcinoma is currently not justified. Postmenopausal women need to be educated about the importance of seeking attention if any vaginal bleeding occurs. All postmenopausal bleeding requires review and appropriate investigation. Women taking tamoxifen have a higher risk of endometrial cancer and should report any bleeding or spotting; however, ultrasound screening is not recommended for asymptomatic women taking tamoxifen. Families with hereditary non-polyposis colon cancer have a higher risk of endometrial cancer and require counselling about this risk. A Pap test is not a screening test for endometrial cancer, but the incidental finding of endometrial cells on a Pap smear in a postmenopausal woman requires investigation.

Gregory Robertson FRCOG, FRANZCOG, CGO

To the Editor: We urge caution about the recently published findings of Durna and colleagues on use of hormone replacement therapy (HRT) by breast cancer patients.1 They found no increase in risk of breast cancer recurrence or reduction in life expectancy in women using HRT after treatment for primary breast cancer, leading them to conclude that HRT seems a safe treatment for women with a history of breast cancer. We believe that their study has many limitations and consequently their conclusions are unfounded Durna's group conducted a retrospective, observational study using unmatched patient groups. The HRT group was statistically younger, with smaller tumours and fewer positive nodes, and thus had better prognosis. The authors discussed regression analyses for age of diagnosis and stage to reduce potential bias, but did not include these data. The omission of tumour grade and receptor status in the analysis is an obvious flaw. The mean duration of HRT use was short compared with many previous studies (mean, 1 year). This is particularly important, as any risk is likely to be cumulative.2 There were also statistically more women in the HRT group who had received HRT before diagnosis, and for a longer duration (mean, 6.5 years v 3 years). This too may bias results, as breast cancer that develops after HRT has been suggested to carry a better prognosis.3 There was also no subgroup analysis of those who took concomitant tamoxifen. Durna and colleagues also do not address the concerns raised by the Women's Health Initiative study, which showed an excess of cardiovascular and thromboembolic events in "healthy" women taking HRT.4 Many of these events occurred in the first years of HRT use, the time assessed in Durna's study. The risks of short-term HRT in breast cancer patients may be not only tumour-related, but may also include cardiac and thrombotic events, which were not specifically considered by Durna and colleagues. Of additional concern is the extensive portrayal in some sections of the media that this study is conclusive regarding the risks of HRT use by women with breast cancer. The importance of correct media interpretation of studies is discussed in the accompaning editorial by Patel and colleagues.5 Despite this editorial and the inadequacies of Durna's study, the results of this study, released through the media, inaccurately suggested safety and even a possible benefit of HRT.6 This simply adds to the "HRT furore". All studies addressing this issue to date have been small and non-randomised, often with no control group or unmatched groups.2 Because of these limitations, no clear recommendation can be made about the safety of HRT in women with breast cancer. Until results are available from rigorous randomised controlled trials, such as the ongoing HABITS (Hormone Replacement Therapy After Breast Cancer — Is It Safe?) study (IBCSG 17-98), we should not be "advocating" HRT to breast cancer patients. For Durna's group to suggest otherwise is very premature. In addition, there are well studied, effective alternatives to HRT for treating menopausal symptoms in breast cancer patients (eg, venlafaxine),7 and these would seem the current safer option.

Theresa M Hayes · Craig R Underhill · Kerrie Clarke · Martin HN Tattersall