Cancer

Major changes to the screening environment dictate a review of this successful program Internationally, cervical cancer prevention programs based on cytological surveillance have been among the most successful public health achievements in modern history. Almost all developed health jurisdictions have tackled the world’s second commonest cancer among women, and implemented successful screening programs. The achievements within each country have been variable, and Australia now has the lowest mortality and second lowest incidence in the developed world1,2 (see Box). However, Australia’s achievements did not come without considerable effort across the community. In the 1980s, many observers noted that ad-hoc screening in Australia was not achieving its potential in cancer prevention. This concern led the Australian Health Ministers’ Advisory Council (AHMAC) to establish a consultative committee, which in turn issued a critical, insightful and comprehensive review of cervical screening and made substantial recommendations to improve the program.1 The report was accepted by AHMAC, and a long process of substantial change began. The AHMAC recommendations involved the historic adoption of a national screening policy in 1991, active recruitment of women for screening, the development and implementation of quality measures across the screening pathway, the establishment of cervical cytology registers in all states and territories, and the endorsement of clinical practice guidelines for the management of screen-detected abnormalities. The success of these changes relied on broad consensus, collaboration and cooperation across the public and private sectors and state, territory and national jurisdictions, and also on the commitment of a broad range of stakeholders. In this issue of the Journal, Canfell and colleagues show that these achievements have been mirrored in the United Kingdom, where similar proportional reductions in incidence and mortality have been noted.3 Nevertheless, absolute incidence and mortality rates in the UK remain substantially higher than those in Australia (Box).1 Since the progressive implementation of the Organised Approach to Preventing Cancer of the Cervix (as the program was titled) began in 1992, both the incidence and mortality of cervical cancer in Australia have been halved.4 Although calculations show that this translates to 1200 women each year whose squamous cancers are being prevented,5 success has come at a cost. Each year, two million women are screened, about 100 000 receive a report of an abnormal smear, and about 15 000 (mostly young) women undergo treatment for a high-grade lesion. Since the 1980s, much about cervical cancer prevention has changed. The appreciation that human papillomavirus (HPV) is the necessary cause of cervical cancer, and increased understanding of the epidemiology of genital HPV infection, the role of acute HPV infection as the cause of most low-grade cervical abnormalities, and the natural history of cervical cancer precursors have all demanded a change in our approach to this disease. Most significantly, a vaccine that successfully prevents the most significant HPV infections, most cervical abnormalities and most cervical cancers is now available through private prescription. An application for public funding of this vaccine is currently before the Australian Government. Despite the dramatic achievements described above, the recent history of introducing change has not been one of consensus and collaboration. An attempt to incorporate HPV natural history into clinical management algorithms through review of the National Health and Medical Research Council (NHMRC) guidelines6 led to widespread controversy in the clinical community.7 A universal mass vaccination program with the HPV vaccine is a cost-effective primary prevention strategy. Markov modelling shows that this will further reduce cervical cancer incidence and mortality, with accompanying substantial reductions in the morbidity associated with our current approach.8 Failure to implement a mass vaccination program will further exacerbate the inequities of access that have been historically associated with cervical cancer prevention in most jurisdictions, such as the lower participation rate for Indigenous women in the Northern Territory that is documented by Binns and Condon in this issue of the Journal.9 Notwithstanding this opportunity, substantial questions remain regarding implementation of the vaccine program. For example, how will the substantial cost of this vaccine be met, even if it is cost-effective? Should the existing cervical screening program be obliged to find savings to cover its cost? Can the current intensive screening program still be justified in a population of young vaccinated women, when the rate of abnormalities will be significantly lower, and the risks of screening will almost certainly exceed the benefits? How will Australia monitor the effectiveness of its vaccination investment? How will the state-based cytology registers incorporate vaccination status into their management recommendations? There are no current plans to establish or incorporate HPV vaccination into any existing register system. Unfortunately, little capacity is evident within current health infrastructure to address any of these issues. The current cervical screening program also has many issues to resolve. There are major questions about the capacity of the cytology workforce to continue servicing a cytology-based program.10 HPV testing offers potential for an efficient reorganisation of the current approach. The registers could contribute to a more organised approach by switching to a recall system where women would be individually recalled for their test when it was due rather than their current reminder system which acts as a safety net for women who are overdue in having the test. However, these changes require substantial cross-sector consultation and consensus. The Australian Screening Advisory Committee was disbanded in May 2006 following an AHMAC review of population health advisory structures. This leaves no national structures available to consider, promote or implement any change within the screening program. Canfell and colleagues seem to be suggesting that the national screening policy in Australia should be modified.3 When the environment of screening is so altered, broader changes are needed than a simple variation to policy on screening interval. Clinicians and consumers do not appear willing to accept any potential increase in cancer rates; they will quickly mobilise to resist such a change. Cervical screening survives on a complex interaction of emotional, professional and commercial interests which are intertwined and sometimes in conflict. Australia needs to undertake a comprehensive review of cervical screening and to carefully consider potential modifications to this outstandingly successful program. Perhaps it’s time in Australia for a “Reorganised Approach to Preventing Cancer of the Cervix”. International variation in incidence and mortality from cervical cancer for selected countries, 2002 Country Incidence per 100 000 women (ASR) Mortality per 100 000 women (ASR) New Zealand 10.0 3.2 United Kingdom 8.3 3.1 Sweden 8.2 3.1 United States 7.7 2.3 Canada 7.7 2.5 Australia 6.9 1.7 Finland 4.3 1.8 ASR = age-standardised rate (World Standard Population). Source: GLOBOCAN.2

Gerard V Wain FRANZCOG, CGO

Inequity in rural cancer survival in Australia is not an insurmountable problem: it is a test of our health systems Australia has lower cancer mortality rates than comparable nations like the United States, United Kingdom, Canada and New Zealand. However, there is increasing evidence that this success may be bypassing the 2.8 million Australians who live in rural and remote Australia.1-3 Indeed, the further from a metropolitan centre patients with cancer live, and adjusting for stage of presentation, the more likely they are to die within 5 years of diagnosis.2-4 Geographical isolation, a relative shortage of health care providers, and a higher proportion of disadvantaged groups such as Indigenous people are acknowledged to be contributing factors.3 How access to specific treatment and support services may explain the differences in cancer survival was a central question of the first national mapping of rural and regional oncology services, commissioned by the Clinical Oncological Society of Australia. The study showed that the availability of oncology services diminished as geographical isolation increased, and that quality and availability of services by location directly influenced survival rates. For all survey criteria assessed, service provision was measurably and significantly poorer in rural and remote centres than in benchmark metropolitan and large regional centres (see Box). Established rural and visiting oncologists, nurses and other cancer care professionals provide a vital service, but they are evidently stretched well beyond capacity. While much of the study’s findings are alarming, the data support our rationale for what we believe are achievable reforms to reduce the geographical inequity in cancer services. Access may not be the only explanation — some remote patients may, for example, choose not to have treatment — but there are ways in which access to quality care can be improved. The centrepiece of our recommendations is the establishment of Regional Cancer Centres of Excellence (RCCEs) in regions with a suitable population. These centres would provide multidisciplinary care, improve support and educational services and, by being mentored by major metropolitan centres, could provide a link to smaller, more remote services. They would also boost access to clinical trials and may provide a critical mass for technological platforms like positron emission tomography scanning. We have pragmatic evidence that RCCEs do work, through the success of a centre in Albury–Wodonga, a former outreach facility that now has five resident oncologists, a clinical trials unit and a two-machine radiotherapy service. Reported benefits include an increase in the number of new patients treated locally from 150 to 750 a year, an eightfold increase in chemotherapy day treatments, establishment of multidisciplinary clinics and more than 10% of new patients participating in a clinical trial.4 The Border Cancer Care Coordination Project, a pilot study funded by the Australian Government, with contributions from the Victorian and New South Wales governments, showed that a modest investment in expanding the Albury–Wodonga service has significantly improved the coordination of care and quality of experience for patients, carers and health professionals. The pilot study employed cancer care coordinators, an oncology social worker, clinical psychologists, a multidisciplinary meeting co-ordinator and a researcher. Information gathered through this project and reported to key stakeholders showed that patients across the wider catchment area were better able to access multidisciplinary care, regardless of their postcode, insurance status or whether they were treated in an acute or community setting. The best way to gradually roll out a network of similar centres is to build them where a radiotherapy unit is in place. Radiation oncology is essential to multidisciplinary cancer care. And, while it is costly in capital outlays and maintenance, and generally immobile, it is the most cost-effective in terms of operational cost versus efficacy.6 A number of non-metropolitan centres have radiotherapy units (Wagga Wagga, Wollongong, Albury–Wodonga, and units are soon to be operational in Coffs Harbour and Port Macquarie in NSW; Ballarat, Bendigo, Geelong and Latrobe Valley in Victoria; and Townsville, Tugun and Nambour in Queensland). There are plans for new units in Darwin, Toowoomba and the NSW far north coast. The combined population of these centres is more than 1.5 million, and an additional 700 000 people are estimated to live within a 150 km radius. Attracting two medical oncologists and a range of allied health service providers to each of these centres would provide a platform for a multidisciplinary team approach to patient care, and enhanced remote supervision by engaged clinicians. It would also be consistent with the Australian Medical Workforce Advisory Committee’s recommendations on practitioner-to-patient numbers. Moreover, a recent unpublished survey by the Medical Oncology Group of Australia showed a high proportion of medical oncology trainees would consider regional practice provided there was adequate support. While awaiting this longer-term solution, we also advocate structural reforms such as a national quality assurance framework (eg, service accreditation, and the use of clinical practice guidelines). Investment and improved innovation in delivering psychosocial support services and the coordination of government-funded travel and accommodation schemes are also required in the interim. Telemedicine is another flexible model that should be supported, as it has proven beneficial in reducing the impact of extreme distance.7,8 Distance education and mentoring are also proving effective.9 RCCEs would provide many of these improvements within their region. Inequity in rural cancer survival is not an insurmountable problem, but it is a real test of our health systems. Investment needs to be made now to deliver long-term benefits. The first step is recognising the extent of the problem and identifying practicable solutions. The second step will require a whole-of-government response. Mapping rural and regional oncology services5 — key findings Nationally, 21% of all 157 rural hospitals administering chemotherapy (RHACs) had a resident medical oncology service; 41% had access to a visiting service, with times of availability ranging from weekly to once in 6 months; 38% had neither a resident nor visiting medical oncology service, and this was more likely to occur as remoteness increased. Chemotherapy-trained nurses administered chemotherapy in 61% of RHACs Australia-wide. Chemotherapy was increasingly administered by people other than a chemotherapy-trained nurse, such as other nurses and general practitioners, as the remoteness of RHACs increased. Medical oncologists write most chemotherapy orders in 100% of benchmark metropolitan centres, but only 58% of RHACs reported that most orders are written by a medical oncologist. The degree of supervision and involvement by medical oncologists or haematologists is not always clear. 22% of RHACs had a dedicated palliative care doctor and 59% had dedicated palliative care nurses. 7% of non-metropolitan hospitals that reported administering chemotherapy had access to a radiation unit — a total of 11 radiation units for all 157 RHACs. Of the 26 available radiotherapy machines in regional centres, fewer than half (46%) were reported as fully staffed. Most RHACs provided access to allied health care services, but many reported long waiting times, out-of-pocket expenses or services restricted to inpatients. Multidisciplinary clinics were held in 43% of RHACs. Dedicated oncology counselling services were available at 39% of RHACs. 61% of all RHACs requested urgent access to psychological services and support; 65% indicated travel support was a problem for rural patients. Patient transport refunds were criticised in many returned surveys. Results from the two metropolitan centres and one large regional centre surveyed were used as a benchmark for comparison of service provision in RHACs.

Craig R Underhill MB BS, FRACP · David Goldstein MB BS, MRCP, FRACP · Paul B Grogan

Stem cells. Controversy at the frontiers of science. Elizabeth Finkel. Sydney: ABC Books, 2005 (vi + 282 pp). ISBN 0 7333 1248 9. There has been no more controversial area in medical science in recent years than the discovery that embryonic and adult stem cells have the potential to generate a range of different tissues, possibly even organ repair and regeneration. As the field has evolved at a blistering pace, several important strands can be discerned. Firstly, the science, while complex, is of great interest to the lay reader. For the public to adequately understand and appraise the importance and potential of these new developments, it is crucial that the current state of scientific development be explained in readily understandable terms. Secondly, the area of stem cell therapy, especially embryonic stem cells and their development, raises many complex ethical issues divisive in our society. Thirdly, Australian scientists have played a major role both in the development of in-vitro fertilisation, the precursor to the embryonic stem cell age, and in the development of embryonic and adult stem cells as potential treatments of the future. Elizabeth Finkel, a distinguished science journalist with a strong background in embryology, has written an intriguing account of the stem cell story. She has brought together all three strands into a very readable account of the field. On one level, for those interested in human stories in science, this is a very good read with great human achievement and political drama. It is also one of the best accounts of the scientific achievements with stem cells to date and of the basis for arising ethical issues. Finkel makes no secret that she is an enthusiast for developing stem cell science as a viable treatment, with both embryonic and adult stem cell research. In some of the examples she covers, most notably Parkinson’s disease, she may overstate the current state of success of stem cell therapies just a little, but does so in an attempt to give a balanced story. One of her key conclusions, that scientific facts must be presented and discussed dispassionately, and that ethical considerations and viewpoints should not be allowed to bias interpretation and presentation of the science to the general public, is a pivotal one in all aspects of science. Stem cell therapy, whether derived from embryonic or adult stem cells, has a great way to go before we will know for sure whether it will be a viable treatment in a major sense for human illness. Elizabeth Finkel’s book makes clear that it is an area of very considerable promise, and I commend this riveting account to all who have an interest in the area. Edward ByrneDean of Medicine, Nursing and Health Sciences, Monash University, VIC Competing interests: Professor Byrne is the current Dean of Medicine at Monash University, where much of the stem cell work in this book was carried out. “Stem cells” won the Science Writer’s Award in the 2005 Queensland Premier’s Literary Awards

Edward Byrne

Objective: To assess the psychosocial impact of the diagnosis of either localised or metastatic prostate cancer (PCA) on patients and their female partners.Design: Observational, prospective study at Time 1 and 6 months later at Time 2 of two groups of couples facing PCA. Time 1 was when patients were first diagnosed with histologically confirmed localised (potentially curable) PCA or metastatic (incurable) PCA.Main outcome measures: Depression and anxiety disorders according to the Diagnostic and statistical manual of mental disorders 4th edition (DSM-IV); psychological distress; marital satisfaction.Results: At Time 1, partners had rates of DSM-IV major depression and generalised anxiety disorder twice those of women in the Australian community, and considerably higher than the patients’ rates. At Time 2, psychological distress in partners had lessened but that in patients had increased. On the other hand, at Time 2, partners’ marital satisfaction had deteriorated.Conclusions: To be fully effective, interventions aimed at reducing the psychosocial morbidity of PCA must involve both patient and partner, rather than the patient alone.

Jeremy W Couper MB BS, MMed(Psych) · Sidney Bloch MB ChB, PhD · Anthony Love PhD · Gillian Duchesne BSc(Hons), MB ChB, MD · Michelle Macvean PhD · David W Kissane MB BS, MPM, MD

To the Editor: Australia’s imminent bowel cancer screening program will revolve around the general practitioner,1-3 whereas, in the United Kingdom, the GP will have virtually nothing to do with the national screening program now underway.4 It is curious that two programs with the same evidence base regarding effectiveness should be so fundamentally different. One explanation could be the differing health care systems in each nation. However, they are more alike than not, so the true explanation for the Australian methodology could rest with the outcome of the Australian pilot studies. If that is the case, then perhaps one should be both alert and alarmed. Given the inequity in access to GPs in Australia, it is not surprising that the Final Evaluation Report5 of the pilot national screening program stated that: Some GPs interviewed in Woolcott’s Qualitative Research focus groups . . . expressed concern over access to FOBTs [Faecal Occult Blood Tests] for people without a fixed address. It was mentioned that this group, particularly Aboriginal and Torres Strait Islander people and people in low socioeconomic groups, particularly homeless people, did not receive invitations to participate in the Pilot. Some GPs commented that the information packs, in both English and the translated versions, were too complicated for people with low literacy and those from culturally and linguistically diverse backgrounds.5 The same report noted that 38% of people overall (men, 42%; women, 34%) and 52% of non-English speakers did not visit their GP after a positive FOBT. Nevertheless, the report favours the continued central role of the GP.5 This is not the case in the UK screening program, which has a more direct approach, with program hubs and associated screening centres — all with defined accountabilities. The Australian approach is to simply add to the workload of GPs — a more pragmatic approach in the short term, but less imaginative. Our program will undoubtedly be a step forward in colorectal cancer prevention. The question is how large that step will be. Reliance on the existing system threatens to reinforce existing health care inequities.

Allan D Spigelman

To the Editor: The recent report by the Multicentre Australian Colorectal-neoplasia Screening (MACS) Group1 offered some intriguing findings. Participation in bowel cancer screening was lower than expected, despite a range of tests being offered. In addition, people offered a choice of different faecal occult blood tests (FOBTs) were less likely to participate than those not offered this choice. The accompanying editorial by Salkeld and colleagues concluded that “Informed consumers making smart choices about screening . . . would be a public health success”.2 We believe the available evidence indicates otherwise. As the MACS Group study showed, participation in FOBTs was lower than in the Australian Government FOBT pilot program,3 and participation in screening by colonoscopy was lower than for other studies, including our recent Australian study.4 They suggested this may be because local general practitioners were not engaged in the project. Our study was designed to address this issue, and concluded that involvement of GPs had a small, non-significant effect on participation rates and no effect on response to invitation.4 This is not to say that involvement of GPs is undesirable. The MACS Group study found participation in FOBTs of 27.4% when only an FOBT kit was provided and a significantly lower participation when a choice of four screening modalities was offered, with an FOBT kit provided (18.6%, P = 0.03). These data confirm the findings of a large multicentre study from the SCORE2 Working Group.5 In that study, participation in FOBT was 30.1%, while participation in either FOBT or flexible sigmoidoscopy, when a choice of the two was offered, was 27.1%. The authors did not offer this analysis, but the difference was again significant (P = 0.015, two-tailed Fisher’s exact test). The editorial by Salkeld et al suggested that the Australian bowel cancer screening program should incorporate decision-support systems to allow informed choice of screening options. The “choice paradox” reported by the MACS and SCORE2 studies argues against this. Further, there is no evidence that decision support improves rates of participation in screening, and some explicit evidence that it has no effect.6 This should not be troubling. At this time, most colon cancer screening is still performed after consultation between patient and doctor, and in this setting informed choice is possible and desirable. Decisionmakers such as the Australian Government Department of Health and Ageing use a different process, which is explicit and quantitative,7 in determining screening policy. With the evidence available, the Australian mass-screening program should offer and evaluate a single test modality.

Douglas R Taupin · Mike Corbett

In reply: Taupin and Corbett contend that the “choice paradox” reported by the MACS Group study argues against decision-support systems to allow informed choice of screening options. That would be true if the purpose of informed choice was simply to increase participation in screening.1 Our point is that the purpose of informed choice is to support an ethical basis for individuals’ decisions about screening.2,3 This can occur within the single-test modality (faecal occult blood tests) of the national screening program. It would be desirable to have decision-support systems embedded in a doctor–patient consultation. But this may not be feasible in terms of screenee access to a general practitioner, nor affordable for the Australian Government — hence our call for a self-directed decision-support system as an adjunct to a doctor-guided system. This is one way of applying the principle that patients should be given unbiased information on the benefits and harms of screening that enables them to make an informed choice about their own participation in screening.4

Glenn P Salkeld · Jane M Young · Michael J Solomon

To the Editor: The National Cancer Control Initiative (NCCI) was established in 1997 jointly by the Department of Health and Ageing and The Cancer Council Australia to “provide timely advice, identify appropriate initiatives, and make specific recommendations to the Commonwealth Government and other key groups regarding the prevention, detection, treatment and palliation of cancer for all Australians”. It has been the only independent group dealing with all aspects of cancer nationally, and incorporating government, non-government, consumer and professional input. On 31 May 2006, it ceased operation due to lack of funding support, and no arrangements have been made to allow continuity between its work and that of a proposed new body, Cancer Australia, which at the time of writing was still not functioning. The NCCI’s contributions include national surveys of colorectal cancer management and of skin cancer incidence and treatment; clinical trials assessing the management of skin lesions in primary care; the first protocols for pilot programs for bowel cancer screening; national programs to promote the implementation of National Health and Medical Research Council guidelines on psychosocial aspects of cancer and on lung and other cancers; programs to improve decision making in prostate cancer screening; a nationally agreed core clinical dataset for cancers; support for cancer registries to include staging and survival information; new methods to establish evidence-based requirements for radiotherapy services; and support for cancer research, for strengthening clinical trials and for consumers’ activities. Since 2000, the small group of NCCI staff has produced seven national workshops, over 30 published reports, and over 60 peer-reviewed articles. These are available online at <http://www.ncci.org.au/> along with current contact details of NCCI staff, and the final report of the NCCI is at <http://www.ncci.org.au/pdf/Final%20 report/NCCI_final_report.pdf>. An independent review in 2004 reported that NCCI’s work was of high quality, well researched, insightful, and cost-efficient, and recommended a considerable increase in funding. A major contribution of NCCI was producing, jointly with The Cancer Council Australia and the Clinical Oncology Society of Australia, the report Optimising cancer care in Australia. The government’s 2004 election policy on cancer (http://www.health.gov.au/internet/budget/publishing.nsf/Content/health-budget2005-hbudget-hfact1.htm) was based partly on this report, and included setting up Cancer Australia, with terms of reference overlapping those of NCCI. The assumption of many policymakers, consumer representatives and cancer experts was that NCCI would become a component of Cancer Australia. This has not happened. Indeed, from 2005, proposals from NCCI for the planned next stages of work on topics including psychosocial aspects of cancer, lung cancer, and primary care in cancer, received no response from the Department of Health and Ageing. With the closure of NCCI, the Director and Deputy Director are relocating overseas, and the highly productive staff members, specifically praised in the independent review, are moving to other roles. The premature demise of the NCCI, before Cancer Australia has started to function, is short-sighted, inefficient, and wastes the experience, resources and staff that NCCI has developed. This finishes a decade-long unique partnership between the Australian Government and non-government national cancer organisations. Cancer Australia will need to develop anew the expertise to identify and address issues in cancer control in Australia, and to link the government and non-government sectors.

J Mark Elwood · Robert C Burton · Michael A Quinn

To the Editor: We read with interest two recent articles and an editorial on the state of medical education in Australia.1-3 As cancer clinicians and academics, and members of the Oncology Education Committee of the Cancer Council Australia, we have been following medical student education about cancer in Australia for almost 20 years and have learned first hand what is not sufficient to achieve change. Highlighting the need: Cancer claims more lives than any other disease4 and is set to increase in incidence by 31% over the next decade,5 yet medical curricula devote little time to cancer education because of competition with other disciplines, historical precedent, personal preferences or just lack of teachers. Developing a national curriculum: An ideal oncology curriculum,6 developed in Australia in 1999, has been endorsed by the International Union Against Cancer, yet has been taken up by a minority of medical schools in Australia. This is largely because of the lack of a national medical curriculum and the absence of a compliance mechanism through national credentialling. Demonstrating deteriorating standards: A comparative study published in 2003 highlighted the fact that recent medical graduates had less exposure to cancer patients than those who graduated 11 years earlier, and that their knowledge was inferior.7 Evidently, community awareness, recommended curricula and evidence of system failure do not effect change. Why? Perhaps because, in the present system, curriculum content is divorced from medical outcomes. There is little or no feedback linking curricula to their consumers: medical students, postgraduate training programs and patients. The Australian Medical Council, the main accrediting body for medical curricula, is more concerned with process than content or outcomes. There is no national outcomes monitoring, nor an exit exam.8 No one knows whether students achieve desired outcomes. We do not even agree on what these are. Outcomes of medical education must feed back to content and process. To do this, we must monitor outcomes nationally, provide feedback to medical schools and have mechanisms to effect change based on such feedback. Without closing the loop, medical education seems to have some features of cancer: vigorous but uncontrolled growth, and uncertain outcome.

Bogda Koczwara · Michael B Barton · Martin H Tattersall · David R Turner · Ian N Olver · Darren L Starmer

Clinical records The details of four patients treated at the Head and Neck Unit, Princess Alexandra Hospital, Brisbane, over a 1-year period are summarised in the table. All four patients presented with progressive trigeminal or facial nerve palsies following excision of cutaneous lesions from the head and neck. Patient Age (years) Sex Presentation History of cutaneous head and neck malignancy Specialties involved Delay in diagnosis Investigations Final diagnosis Management Patient 1 40 male 3 years’ progressive paraesthesia of the left upper lip and cheek Nasal tip lesion removed with cryotherapy: no histology available General practice, dermatology, otolaryngology 3 years MRI PNS (SCC) along V2 Intracranial/skull base surgery with postoperative radiotherapy Patient 2 41 male 8 months’ progressive left cheek paraesthesia, jaw pain and trismus Excision of a left lower lip SCC 2 years previously: histology showed small nerve PNS, so postoperative radiotherapy given General practice, maxillofacial, neurology, otolaryngology 6 months MRI (showed hyperintensity of the left masseter consistent with denervation changes) Masseteric muscle biopsy PNS (SCC) along V2 and V3 extending to the pons Palliative radiotherapy Patient 3 67 female 2.5 years’ progressive left facial nerve palsy Extensive facial SCCs, including an aggressive recurrent right cheek SCC treated with radical excision and radiotherapy Neurology, ophthalmology, otolaryngology 2.5 years MRI PNS (SCC) along VII and V2 Intracranial/skull base surgery with postoperative radiotherapy Patient 4 72 female 5 months’ progressive left facial nerve palsy and left forehead and cheek paraesthesia Two skin lesions excised from the right (contralateral to nerve palsies) nasolabial sulcus 20 years previously: no histology available Otolaryngology 5 months Initial MRI (Box 1) reported as “normal”, although on retrospective review PNS was seen. Subsequent MRI (Box 2) showed extension of the tumour to the pons. PNS (melanoma) along V2 and V3 extending to the pons Palliative care MRI = magnetic resonance imaging. PNS = perineural spread. SCC = squamous cell carcinoma. V2 = maxillary division of trigeminal nerve. V3 = mandibular division of trigeminal nerve. VII = facial nerve. The incidence of non-melanotic head and neck skin cancers in Queensland is among the highest in the world.1 Perineural spread (PNS) from these lesions involves either small nerves, identified at pathological examination (incidental), or large nerves, presenting clinically as cranial nerve palsies. Basal cell carcinoma is the more common skin cancer, but incidental PNS is most frequently associated with squamous cell carcinoma.2 In 32 out of 34 patients over a 5-year period, isolated major nerve PNS was due to squamous cell carcinoma (unpublished data). PNS from melanoma and microcystic adnexal carcinoma has also been described.3,4 Because many clinicians are not familiar with PNS involving large cranial nerves, the diagnosis can easily be missed or delayed. The disease is associated with high treatment morbidity and poor prognosis once clinical or radiological evidence becomes apparent, with a 5-year survival rate of 20%–30%.5 Early detection of PNS in large cranial nerves is essential, as the condition is often unsalvageable once the tumour has spread through the skull base. The facial and trigeminal nerves are most commonly affected,6 although forehead tumours can gain access to the orbit via the ophthalmic nerve.7 Symptoms of trigeminal nerve infiltration include formication, dysaethesia, paraesthesia, numbness and pain (often severe and “electric shock-like” in nature).8 Slowly progressive facial nerve palsy may represent seventh cranial nerve infiltration or infiltration within the parotid, whereas diplopia and visual impairment indicate advanced orbital disease. These symptoms can mimic other diagnoses, such as Bell’s palsy or trigeminal neuralgia, but almost always manifest as slowly progressive and irreversible palsies. Close follow-up of patients to ensure resolution of symptoms is mandatory. The four patients we have described illustrate delays between clinical presentation and diagnosis. These delays could have been avoided by establishing the link between unresolving cranial nerve palsies and excision of cutaneous lesions from the head and neck. Patients 2 and 3 had a history of aggressive squamous cell carcinoma of the face treated with radical excision and postoperative radiotherapy. Advanced, recurrent skin squamous cell carcinomas have a higher incidence of PNS, particularly when located close to a cranial nerve, and should alert the clinician to the possibility of neural metastasis.9 Tumour size before excision, postoperative defect size, subclinical extension and Moh’s micrographic surgery levels are significantly larger in patients with PNS than in patients without PNS.10 PNS can be subtle and missed on initial pathology but, because of the propensity for local recurrence, most specialist multidisciplinary units that deal with skin cancer will recommend adjuvant radiotherapy, particularly if the lesion is excised from the trigeminal nerve distribution. In Patients 1 and 4, no histology was available. Small skin lesions are often treated with cryotherapy or curettage, resulting in no pathological report. However, these lesions may still have a propensity for PNS, so their excision should be elicited in the history. In Patient 4, the skin lesions were excised from the side of the face contralateral to the cranial nerve palsies and were unlikely to represent the primary disease. Nevertheless, this case illustrates that patients with a history of cutaneous lesions from any site on the head and neck are at risk of developing PNS. These cases also illustrate that the interval between excision of a lesion and presentation of PNS can be long.11 Clinicians should hold a high index of suspicion even if the interval is several years. A further source of delay is that patients are seen by a variety of clinicians before diagnosis. Cross-referral for second opinions is common, resulting in further delay. Patients 1–3 illustrate how the unfamiliarity of clinicians with the disease process resulted in patients seeking opinions from several specialties before definitive diagnosis. In addition, investigations may be performed to exclude a different pathology or misinterpreted because the clinician is unaware of the phenomenon, resulting in further delay. In Patients 2 and 4, initial imaging revealed changes compatible with PNS, but these were not recognised, either because the radiologist was not familiar with the entity or because the referring clinician may not have raised the possibility of PNS. In Patient 2, the hyperintensity of the masseter muscle on magnetic resonance imaging (MRI) led the clinician to suspect a primary muscular disorder, instead of the correct interpretation of denervation changes from trigeminal nerve involvement. The patient underwent an unnecessary muscle biopsy. Earlier detection may have resulted in Patients 2 and 4 being treated with curative intent instead of palliative care. High resolution MRI is the investigation of choice, and may identify the earliest changes of PNS. However, disease may not be radiologically apparent until it has reached the orbit, cranial fossa or the skull base foramina. Computed tomography (CT) identifies the disease at a late stage when the tumour has eroded adjacent bony margins. MRI has the added advantage of defining the relationship of the perineural tumour to important anatomical landmarks such as the cavernous internal carotid artery; this is important when planning a resection or biopsy. However, subtle changes on MRI may be missed even by experienced radiologists and, given a strong clinical suspicion with normal imaging, nerve biopsies should be performed. Presently, positron emission tomograph (PET) scanning has no role to play in the staging of PNS. Delayed diagnosis of major cranial nerve PNS may result in devastating outcomes for patients, so early detection is crucial. Patients who present with slowly progressive cranial nerve palsies with a history of head and neck cutaneous malignancies should be investigated for PNS with a high index of suspicion. We recommend that all patients who undergo excision of high risk skin malignancies should be advised to seek a medical opinion if they develop facial numbness or weakness in subsequent years. 1 Coronal T2-weighted MRI images of Patient 4 These images were reported as “normal”, although retrospective review shows perineural spread of melanoma with thickening and nodularity along the left V2 (A), V3 (B) and the trigeminal ganglion (C). MRI = magnetic resonance imaging. 2 Contrast-enhanced T1-weighted MRI images of Patient 4 The images show perineural spread of melanoma with perineural thickening and enhancement along the left V2 (A), V3 (B), the trigeminal ganglion (C) and the trigeminal nerve as it exits the pons (D). MRI = magnetic resonance imaging.

Giles C Warner MSc, MD, FRCS · Mitesh Gandhi MRCP(UK), FRCR, FRANZCR · Benidict Panizza MB BS, MBA, FRACS

The opportunity for informed choice in screening is limited Commencing in mid 2006, the Australian Government will phase in a national bowel cancer screening program for men and women who turn 55 or 65 years of age, and for those who participated in the government’s pilot screening program, conducted from November 2002 to June 2004.1 Eligible people will be invited to complete an immunochemical faecal occult blood test (FOBT) in the privacy of their own home and mail it in for analysis.2 Consumers will not be offered a choice of screening test. The government came to this position after commissioning a review of the costs, benefits and harms of different screening options3 and evaluating the pilot screening program.1 The study by The Multicentre Australian Colorectal-neoplasia Screening (MACS) Group in this issue of the Journal (A comparison of colorectal neoplasia screening tests: a multicentre community-based study of the impact of consumer choice)4 suggests that participation in screening does not differ significantly between different screening tests that might be offered. The implication is that consumer choice can be taken out of the equation if maximising participation is the primary objective of screening. If consumer choice does not influence participation, then why not offer a range of screening tests? This invites two prior questions — to what extent should the Australian Government be concerned about consumer choice and participation, and what criteria should be applied to determining screening options? For decades, Australia has accepted the World Health Organization guidelines for evaluating the worth of screening. These guidelines, recently updated, state “. . . in screening there is an ethical responsibility to conduct programs that will be of overall benefit to those who are screened and will minimize harm and anxiety that will arise. It is not simply the offering of medical tests for people to accept or reject as they wish. This responsibility implies that if evidence is not available from valid studies on the effectiveness of screening, screening should not be offered.”5 Although one in six participants in the MACS Group trial participated in a screening strategy other than FOBT,4 neither flexible sigmoidoscopy, computed tomography colonography nor colonoscopy meet the WHO criteria for a screening test. As yet, there is no trial evidence that any of these tests reaches an acceptable ratio of population benefits to harms and costs that would warrant their inclusion in a national screening program. The results of the MACS Group trial raise important questions about whether participation in screening is an appropriate measure of success and whether participation itself is an adequate measure of consumer choice. The traditional view, one shared by the updated WHO guidelines, is that participation is a measure of success.5 All things being equal, the more people who are screened, the greater the reduction in bowel cancer mortality in the population. That line of reasoning is incontestable. What is contestable is whether people who participate in screening make an informed choice. The MACS Group suggest that the one reason why their participation rates (averaging 20.9% over all screen tests) were lower than the government pilot projects (45.4%)1 and other international programs is that the Group were required to “present the invitation as a clinical research project with due informed consent” (our emphasis). This, argues the MACS Group, may have contributed to a lower participation rate. They then suggest that a “guided choice” following formal clinical review might improve participation. The Australian Government should seriously consider providing a decision-support system that allows consumers to decide whether they want to take up the offer of screening, based on information of benefits, harms and the process of testing. This should include a guide to screening options. Not everyone will want or need a “guided choice”. Our previous study of consumer choice of FOBT screening found that a third of the target group opted for screening no matter what the ratio of harms to benefits, 55% took up the offer of a guided choice (weighing up the benefits and harms), and 12% chose outright not to be screened.6 Even if 30% of the target screening group take up the offer of a guided choice by a general practitioner, based on the 75% Medicare rebate for a level-B GP consultation, the cost per life-year saved (LYS) of biennial FOBT screening without a routine GP consultation would increase from about $13 5007 to $21 000 per LYS. If 70% of the target population opt for a GP visit, the cost per LYS is $31 300 — more than double the cost effectiveness ratio for a screening program without a routine visit to the GP. Even so, this figure is comparable to other cancer screening programs. The challenge is to develop an affordable decision-support system — one that is either self-directed or one that offers restricted access to an additional GP consultation. This applies equally to those aged under 55 years who will not be eligible for screening in the national program. Unless the national program actively engages the community, GPs and pharmacists in screening and diagnostic assessment of people with a positive FOBT, the opportunity for an informed choice and participation is limited. A key question for the National Bowel Cancer Screening Program is whether setting participation targets and using them to measure the success of screening is appropriate. Falling short of a 70% target participation rate shouldn’t be taken as a public health failure if it can be shown that consumers have had an opportunity to make an informed choice (alone or with their GP), using a decision-support system if they wish to do so. Informed consumers making smart choices about screening — now that would be a public health success.

Glenn P Salkeld GradDipHealthEcon, MPH, PhD · Jane M Young MPH, PhD, FAFPHM · Michael J Solomon MB BCh, MSc, FRACS

Objective: To describe the management of and outcomes in a population-based cohort of patients with newly diagnosed glioma.Design, setting and patients: Retrospective cohort study of patients with glioma newly diagnosed over the period 1998–2000 in Victoria. Patients were identified from the population-based Victorian Cancer Registry (VCR). Doctors involved in managing the patients were surveyed by a questionnaire sent out in 2003. The cohort was followed until the end of 2004 to obtain at least 4 years’ follow-up data on all patients.Main outcome measures: Reported treatment, referral patterns and survival rates.Results: Over the study period, 992 cases of glioma were identified; 828 completed surveys on eligible patients were obtained (response rate, 93%); 473 patients (57%) had glioblastoma multiforme (GBM); 105 patients (13%) diagnosed with “glioma” had had no histological confirmation. Complete macroscopic resection was performed in 209 patients (25%); 612 patients (74%) were referred for radiotherapy and 326 (54%) for chemotherapy; 39 (5%) were enrolled on a clinical trial. Median survival was 9.2 months for all patients and 7.4 months for patients with GBM.Conclusions: This is the largest reported glioma management survey in the world to date. Much of the patient demographics and approach to treatment were as expected and represent a reasonable “standard of care”. However, there are some areas for improvement, including the absence of histological diagnosis in some patients, lack of multidisciplinary care, low clinical trial enrolment and poor use of ancillary services.

Mark A Rosenthal MB BS, FRACP, PhD · Katharine J Drummond MB BS, FRACS · Michael Dally MB BS, FRANZCR · Michael Murphy MB BS, FRACS, MD · Lawrence Cher MB BS, FRACP · David Ashley MB BS, FRACP, PhD · Vicky Thursfield BSc, GradDipAppl Stats · Graham G Giles MSc, PhD

New tumour testing methods can improve the accuracy of diagnosis Although a strong genetic predisposition to colorectal cancer (CRC) is rare, it is important because of its large contribution to CRC diagnosed before the age of 50 years and because mortality from CRC can be reduced by appropriate management. There are currently limitations in determining whether a case of CRC is “sporadic” or whether it might be related to an inherited predisposition. However, Australian research that examines the utility of new diagnostic tools to help diagnose genetic tendency to CRC may be showing us a way forward.1,2 What is hereditary non-polyposis colorectal cancer?The two best-characterised high-risk inherited syndromes are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer (HNPCC) — sometimes known as Lynch syndrome. Both are inherited as autosomal dominant traits. Familial adenomatous polyposis can usually be readily diagnosed on the basis of clinical findings alone, when an individual develops CRC at a relatively young age on a background of colorectal adenomatous polyposis (mostly with more than 100 adenomas). HNPCC cannot usually be readily diagnosed. HNPCC accounts for about 1%–4% of all CRC, but up to 10% in patients younger than 50 years at diagnosis. It is caused by a germline (heritable) mutation in one of a family of genes known as the DNA mismatch repair genes: hMLH1, hMSH2, hMSH6 and hPMS2.3 HNPCC is characterised clinically by an early age of onset of CRC, a predisposition for proximal colonic cancers, and a tendency to develop multiple CRC, along with an increased risk of some extra-colonic malignancies, including cancers of the uterus and ovary, stomach, small bowel, biliary tree, ureter, renal pelvis, pancreas and brain. The family history is often complex. What are the difficulties in diagnosing HNPCC?Traditionally, HNPCC has been suspected in families where the family history of cancer meets the modified Amsterdam criteria.4 These require a family to have at least three close relatives in two generations diagnosed with cancer of the colon, rectum, endometrium, small bowel, ureter or renal pelvis, with at least one diagnosed before age 50 years. One problem is that not all “Amsterdam positive” families will be proven to have HNPCC and, conversely, some families with proven HNPCC do not meet these criteria. Family history alone is not enough — a diagnosis of “suspected HNPCC” may be based on verified clinical and pathological information from the family pedigree, but the diagnosis of HNPCC is ultimately confirmed by the demonstration of a family germline mutation in one of the mismatch repair genes. This is done by taking blood from one of the affected family members and searching the mismatch repair genes to determine whether a causative mutation can be found. However, a mutation cannot be found in every family, as mutations may be missed or mutations may be present in other genes that are not yet identified. This means that if the family history is strong (Amsterdam positive) and the genetic test (mutation search) fails to identify a mutation in an affected family member, the test result should be considered “inconclusive” and all relatives remain at potentially high risk. Only when a causative mutation in one of the mismatch repair genes has been identified can other at-risk adult family members be offered “predictive” genetic testing to determine their risk. Importantly, those found not to carry the family mutation should be considered at the average population risk for cancer, and they (and their offspring) can be spared additional cancer screening and concern. At present, many families with a family history that meets or approaches the Amsterdam criteria are offered this expensive approach to germline genetic testing; few are found to have proven HNPCC. How are these difficulties being addressed?The accurate detection of HNPCC has improved recently for a number of reasons. The first is an increasing awareness of family history as a risk factor for CRC. Clinical practice guidelines assist in estimating CRC risk based on family history.5,6 For those with a more complex family history, referral to a family cancer clinic may be appropriate. These clinics have been developed to provide cancer risk assessment, surveillance, and prevention strategies, with genetic counselling and testing when appropriate. Finally, we now have improved diagnostic tools, including molecular testing of tumours for microsatellite instability and immunohistochemical staining of tumour tissue for mismatch repair proteins, which can be used to help investigate a history of “suspected HNPCC”. Additional molecular tumour tests are in development. Molecular testing for microsatellite instabilityMicrosatellite instability is one of the hallmarks of HNPCC-related cancers and is due to unrepaired mutations in repetitive sequences of DNA known as microsatellites. CRCs that occur in patients with HNPCC tend to be right-sided, mucinous, poorly differentiated and characterised by the presence of tumour infiltrating lymphocytes. On molecular testing, these tumours show high levels of microsatellite instability. The Bethesda guidelines7 were developed to provide criteria for testing tumours for microsatellite instability in an individual affected family member to assist in the diagnosis of HNPCC. These guidelines suggest that all people with CRC diagnosed before the age of 50 years should have microsatellite instability testing to look for possible HNPCC. However, another limitation presents itself. Although high levels of microsatellite instability are seen in most HNPCC-related tumours, microsatellite instability is not exclusive to HNPCC. Some people develop sporadic cancers with high levels of microsatellite instability, unrelated to an inherited defect in mismatch repair; around 10%–15% of sporadic colorectal cancers will exhibit high levels of microsatellite instability. This tends to occur in older women with right-sided cancers, often mucinous, with poor glandular differentiation (as per HNPCC), but with no associated HNPCC family history. In patients with sporadic CRC with high levels of microsatellite instability, the defect in mismatch repair is not heritable and occurs only in the tumour as a result epigenetic silencing of the promoter region of hMLH1. It does not alter the risk of CRC in offspring, so it is important to differentiate this from HNPCC. Tumour BRAF gene mutations occur in most of these sporadic cancers, but virtually never in HNPCC-associated cancers with high levels of microsatellite instability. The presence of a BRAF gene mutation in a tumour with high levels of microsatellite instability makes it more likely to be a sporadic CRC; however, the use of tumour testing for BRAF mutation is speculative at this stage and it is not yet readily available. Immunohistochemical stainingAnother approach used to improve the accuracy of diagnosis of HNPCC is the use of immunohistochemical staining in suspected cases. Immunohistochemical staining uses antibodies to the proteins encoded by the four relevant mismatch repair genes (hMLH1, hMSH2, hMSH6 and hPMS2) to test for the expression of these proteins in tumour tissue. Absence of mismatch repair proteins is often seen in HNPCC and may be specifically related to the gene in which a germline mutation may subsequently be found; that is, the absence of hMSH2 protein in cancer cells usually indicates a germline mutation in hMSH2. However, once again, this absence of staining is not specific to HNPCC — loss of expression of hMLH1 due to somatic inactivation of hMLH1 does occur in sporadic cancers. How is Australian research contributing in this field?Southey et al have recently conducted an analysis of the use of tumour testing to prioritise mismatch repair germline testing in an Australian population-based study of early onset (< 45 years old) CRC.1 In 131 patients, unselected for family history, they found 18 with germline mutations in one of the mismatch repair genes (indicating HNPCC). Based on family history alone (the Amsterdam criteria), only half of these would have been identified, indicating that tumour testing (specifically immunohistochemical staining) is a very useful adjunct to diagnosis, and more sensitive than family history. Ward et al, also Australian, have since published similar findings.2 Immunohistochemical staining has an advantage over microsatellite instability testing in that it is relatively inexpensive, can be conducted in a routine pathology laboratory (rather than a molecular laboratory), and the immunohistochemical staining test identifies the specific mismatch repair gene in which to search for a germline mutation, thereby saving money by directing the mutation search. However, although immunohistochemical staining is promising as a tool to increase diagnostic accuracy for HNPCC, it may be too early to apply this test routinely at diagnosis to all patients with CRC. There are still some problems with tumour testing. Some patients have loss of staining on immunohistochemical staining without a demonstrable mismatch repair germline mutation, indicating a lack of specificity, although this may change as germline testing improves. Immunohistochemical staining utilises antibodies that are not commonly used in pathology laboratories, and staining may be patchy and difficult to interpret for those who do not use these antibodies routinely. Moreover, there is generally a lack of understanding concerning the interpretation of loss of stain — loss of hMLH1 in a patient with an older onset CRC, without family history, usually indicates a sporadic cancer rather than HNPCC, but some of these families are now inappropriately being referred to family cancer clinics as “possible HNPCC”. Finally, some argue that tumour testing is a surrogate genetic test and so requires genetic counselling and fully informed consent. However, tumour testing should be simply viewed as a useful adjunct to HNPCC diagnosis, in that an abnormal finding on immunohistochemical staining raises the possibility, rather than the certainty, of a familial predisposition to CRC. Where to from here?Tumour testing could now be used as a “triage” measure to assist referral to a family cancer clinic for further assessment and germline testing, if appropriate. It is especially applicable when the family history approaches, but does not quite meet, the Amsterdam criteria for suspecting HNPCC or when CRC is diagnosed at an early age (younger than 50 years). However, before this can become routine, immunohistochemical staining testing for HNPCC may need to be standardised, and laboratories validated through the Royal College of Pathologists of Australia to ensure reliable results. Even so, for now, the best diagnostic precision is still achieved by a combined analysis of all the variables: family history, and clinical and pathological findings, as well as results of genetic tests.

Judy A Kirk MB BS, FRACP

The reduction in the incidence of contralateral breast cancer in women treated with adjuvant tamoxifen provided a model for prevention using endocrine agents. Oestrogen-receptor-positive cancer can be prevented with tamoxifen, but side effects limit its clinical utility, and the risk–benefit ratio is not sufficiently high to routinely recommend tamoxifen as a preventive agent. Agents being evaluated in prevention trials include raloxifene and the aromatase inhibitors; these are expected to be at least as effective as tamoxifen and to have fewer side effects. Core needle biopsy (providing histological information) and high-resolution breast ultrasound enhance preoperative assessment of breast cancer. Mammography remains the only screening test shown to reduce breast cancer deaths in randomised trials. Magnetic resonance imaging may have a role in screening women with inherited mutations of the breast cancer genes. Sentinel lymph node biopsy accurately assesses lymph node status and is associated with less morbidity than axillary dissection. Where the biopsy is negative (no histologic evidence of metastases), no further axillary treatment is necessary. Breast reconstruction after mastectomy can produce good cosmetic results, especially where autologous tissue is used. Myocutaneous flaps using latissimus dorsi or transverse rectus abdominus muscles are increasingly popular. Adjuvant trastuzumab therapy in patients whose tumours overexpress HER2 (growth factor receptor) can reduce recurrence rates and improve survival. Neoadjuvant endocrine therapy (as an initial treatment before surgery) is an underutilised treatment in postmenopausal women with oestrogen-receptor-positive large operable or locally advanced cancers. It makes more patients suitable for surgery and offers others the choice of breast conservation.

Nehmat Houssami PhD, FAFPHM, FASBP · Jack Cuzick PhD · J Michael Dixon MD, FRCS, FRCP

Objective: To describe the workload profile in a network of Australian skin cancer clinics.Design and setting: Analysis of billing data for the first 6 months of 2005 in a primary-care skin cancer clinic network, consisting of seven clinics and staffed by 20 doctors, located in the Northern Territory, Queensland and New South Wales.Main outcome measures: Consultation to biopsy ratio (CBR); biopsy to treatment ratio (BTR); number of benign naevi excised per melanoma (number needed to treat [NNT]).Results: Of 69 780 billed activities, 34 622 (49.6%) were consultations, 19 358 (27.7%) biopsies, 8055 (11.5%) surgical excisions, 2804 (4.0%) additional surgical repairs, 1613 (2.3%) non-surgical treatments of cancers and 3328 (4.8%) treatments of premalignant or non-malignant lesions. A total of 6438 cancers were treated (116 melanomas by excision, 4709 non-melanoma skin cancers [NMSCs] by excision, and 1613 NMSCs non-surgically); 5251 (65.2%) surgical wounds were repaired by direct suture, 2651 (32.9%) by a flap (of which 44.8% were simple flaps), 42 (0.5%) by wedge excision and 111 (1.4%) by grafts. The CBR was 1.79, the BTR was 3.1 and the NNT was 28.6.Conclusions: In this network of Australian skin cancer clinics, one in three biopsies identified a skin cancer (BTR, 3.1), and about 29 benign lesions were excised per melanoma (NNT, 28.6). The estimated NNT was similar to that reported previously in general practice. More data are needed on health outcomes, including effectiveness of treatment and surgical repair.

David Wilkinson MB ChB, DSc, FRACGP · Deborah A Askew BAppSci, MHlthSci, PhD · Anthony Dixon MB BS, FACRRM

Loss of bone mineral density with androgen deprivation therapy (ADT) for prostate cancer is well recognised, with significant loss of bone mineral density (BMD) occurring within 12 months of starting therapy. With ADT, annual loss of BMD is about 2%–8% per year at the lumbar spine and 1.8%–6.5% at the hip; the loss appears to continue indefinitely while treatment continues, and there is no recovery after therapy is ceased. 19.4% of men surviving at least 5 years after diagnosis of prostate cancer have a fracture if treated with ADT compared with 12.6% of men not receiving ADT; this is equivalent to one additional fracture for every 28 men treated with ADT. Vitamin D deficiency exacerbates the development of osteoporosis, so vitamin D status should be evaluated before commencing ADT in men with prostate cancer. Treatment with bisphosphonates (zoledronate, pamidronate and alendronate) in men treated with ADT have been shown to prevent bone loss in prospective studies and to increase BMD in one randomised controlled trial; bisphosphonates have not been shown to prevent fractures in men with prostate cancer. Further prospective trials are required to assess the efficacy and cost-effectiveness of bisphosphonates in men with prostate cancer who require treatment with ADT. All doctors need to take an active role in monitoring bone health in patients with prostate cancer requiring ADT.

D Jane Holmes-Walker PhD, MB BS, FRACP · Henry Woo MB BS, FRACS · Howard Gurney MB BS, FRACP · Viet T Do MB BS, FRANZCR · David R Chipps PhD, MB BS, FRACP

Concise clinical oncology. Clive Peedell. Sydney: Butterworth-Heinemann, 2005 (xiii + 320 pp). ISBN 0 7506 8836. Exactly as the title suggests — concise and to the point! It is robustly constructed, and ideal in size (190 x 130 mm — fits in a coat pocket), number of pages and detail for medical students or junior clinicians in any specialty, general practitioners, or junior trainees in one of the oncology specialties. Oncology trainees in later years would be better served by a more comprehensive textbook. The author is a radiation oncologist at James Cook University Hospital in Middlesbrough, United Kingdom, and the information presented is up-to-date, succinct and relevant. It is easy to navigate, with good use of fonts, as well as colour, tables and figures to embellish the text. It is well set out with an excellent table of contents and index. Sections include oncology principles, A–Z of cancers (which occupies about half of the book), complications and emergencies, as well as a short A–Z of chemotherapy drugs, and useful websites. There are three to five references after each chapter for readers who want more detail, mostly reviews in readily accessible online journals. With each cancer in the A–Z section, the text is divided into background, presentation, diagnosis and staging, management, and future perspectives. This allows easy navigation for the busy general clinician. All cancers are covered but, as is appropriate, the more common cancers, such as breast, colorectal and lung cancer, occupy more pages. Some of the information about cancer management and prognosis may change with time, but the future perspectives section gives this book a longer shelf life than most. Stephen P AcklandMedical Oncologist Newcastle Mater Misericordiae Hospital, NSW

Stephen P Ackland

Ami Schattner,* Noa Ben-Baruch† * Associate Professor of Medicine, † Head, Breast Cancer Unit, Hebrew University Hadassah Medical School, Kaplan Medical Centre, Bilu Junction, Rehovot, 76100, Israel. amiMDATclalit.org.il To the Editor: We describe a patient with malignant ascites and bacterial peritonitis, with no apparent intra-abdominal source of infection. A 56-year-old woman with advanced breast cancer was admitted to hospital with a 10-day history of diffuse abdominal pain, umbilical tenderness, and increasing abdominal girth. Breast cancer had been diagnosed 13 years before admission (T2 N0 M0) and treated with radical mastectomy and adjuvant chemotherapy. Five years before admission, disease had recurred at the chest wall, and 2 years before, liver metastases were found. Chemotherapy had failed, and her only current treatment comprised capecitabine and analgesics. On admission, the patient had tachycardia (110 beats per min), tachypnoea (26 breaths per min), blood pressure of 115/80 mmHg, and no fever or signs of sepsis. Examination showed evidence of local recurrence around the left mastectomy scar, and marked ascites with discoloration, warmth, tenderness and a diffuse infiltration over the umbilicus. There were no signs of peritoneal irritation, nor leg oedema. Blood test results were in the normal range, except for mild leukocytosis (10.6 × 109 cells/L; reference range [RR], 3.8–9.8 × 109 cells/L), with left shift (86% neutrophils, and 6% lymphocytes; RR, up to 67% neutrophils, and at least 32% lymphocytes). X-ray did not show abdominal free air. Abdominal computed tomography revealed ascites, retroperitoneal lymph nodes, omental and umbilical infiltration, and the known liver metastases without signs of portal hypertension. Peritoneal tap removed 2800 mL of fluid. Examination of the fluid revealed a white blood cell count of 2 × 109 cells/L (80% neutrophils), glucose concentration of 790 g/L, and albumin concentration of 22 g/L (serum–ascites albumin gradient, 0.7; a gradient < 1.1 indicates that the patient does not have portal hypertension). Gram stain of the ascitic fluid revealed gram-positive cocci, and culture identified Staphylococcus aureus. Cytological examination showed sheets of atypical enlarged epithelial cells highly suggestive of malignancy. Therapy was begun with parenteral cloxacillin and ciprofloxacin, but the patient died shortly after. This patient’s condition is unlikely to have been spontaneous (“primary”) bacterial peritonitis, which usually occurs in patients with liver cirrhosis, portal hypertension and ascites with high serum–ascites albumin gradient,1 and occasionally in patients with malignant ascites.2 However, in our patient, infection may have originated from the umbilical metastasis. The umbilicus has a direct connection with the intra-abdominal cavity and is also connected to a number of intra-abdominal organs via embryological remnants, such as the umbilical vein and the urachus. Both routes may be involved in the spread of malignant tumour to the umbilicus,3 but spread may also be in the opposite direction, causing peritonitis. This diagnosis may be missed by physicians who may not notice anything new in a patient with longstanding malignant ascites, and may fail to consider bacterial peritonitis, a treatable condition.

Ami Schattner · Noa Ben-Baruch

The number of skin cancer clinics functioning within Australia’s primary care environment is increasing rapidly, and significant concerns have been raised about the type and quality of work done by some doctors in some clinics. Mainstream general practice is threatened by perceived fragmentation, and specialist practice in dermatology and plastic surgery is threatened by encroachment into their domains of practice. We propose an agenda of training, standards, accreditation, audit and research to ensure that skin cancer clinics provide optimal health outcomes for patients.

David Wilkinson MB ChB, FRACGP, DSc · Scott Kitchener MB BS, DrPH, FAFPHM · Peter Bourne MB BS · Anthony Dixon MB BS, FACRRM

Research shows that a large proportion of shade structures provide insufficient protection against the sun’s ultraviolet light. Shade creation guidelines need to be updated. Community organisations such as child care centres and schools that need to provide effective shade are hindered by cost and building regulations. The protective function of shade structures is more important than their aesthetic appeal.

David J Turnbull PhD · Alfio V Parisi PhD

CorrectionRe: “Long-term trends in cancer mortality for Indigenous Australians in the Northern Territory”, by John R Condon, Tony Barnes, Joan Cunningham and Bruce K Armstrong, in the 17 May 2004 issue of the Journal (Med J Aust 2004; 180: 504-507). Box 1 on page 505 of this article inadvertently included some incorrect data. The corrected table is shown with the changes in bold text. The html and pdf versions of this article were corrected on 1 December 2005. In summary: for oesophageal cancer, the corrected mortality rate ratios (NT Indigenous to total Australian) are higher than the published results in all age categories; for stomach cancer, the corrected rate ratio for the 0–64 age group is lower than the published figure, and the all-ages result is now reported because the difference between the younger and older age groups is no longer statistically significant (P = 0.06); for cancer of the liver and gallbladder, the corrected rate ratios are lower in the 0–64 years and all-ages groups; and there are also very slight changes for breast and lung cancers. These changes do not alter the inferences that might reasonably be drawn from the results in the table, or the overall findings of the study and their interpretation. Cancer mortality rate ratios* (NT Indigenous population compared with the total Australian population), by age group, 1991–2000 Site/type of cancer 0–64 years 65 years and over All ages† Interaction P value† Oropharynx 8.0 (5.5, 11.6) 2.0 (0.8, 4.8) — < 0.01 Oesophagus 2.9 (1.5, 5.6) 1.2 (0.5, 2.9) 1.9 (1.1, 3.2) 0.11 Stomach 1.4 (0.6, 3.0) 0.2 (0.0, 1.2) 0.7 (0.3, 1.4) 0.06 Colon and rectum 0.9 (0.5, 1.4) 0.2 (0.1, 0.6) — 0.01 Liver and gallbladder 5.5 (3.6, 8.6) 5.8 (3.9, 8.6) 5.7 (4.2, 7.6) 0.88 Pancreas 4.1 (2.7, 6.3) 1.1 (0.5, 2.2) — < 0.001 Lung 3.6 (2.9, 4.5) 1.4 (1.0, 1.9) — < 0.001 Melanoma 0.0 0.0 0.0 na Breast 0.8 (0.5, 1.3) 0.9 (0.4, 1.8) 0.8 (0.6, 1.3) 0.86 Uterus‡ 3.4 (1.1, 10.7) 2.5 (0.8, 7.6) 2.9 (1.3, 6.4) 0.68 Cervix 8.0 (5.2, 12.4) 10.1 (5.4, 19.1) 8.6 (6.0, 12.3) 0.56 Ovary 1.0 (0.4, 2.6) 1.3 (0.5, 3.5) 1.1 (0.6, 2.2) 0.67 Prostate 0.9 (0.2, 3.6) 0.3 (0.1, 0.8) 0.4 (0.2, 0.8) 0.23 Bladder 1.5 (0.4, 6.1) 0.5 (0.1, 1.9) 0.7 (0.3, 1.9) 0.24 Kidney 0.3 (0.0, 2.2) 0.0 0.1 (0.0, 1.0) 1.00 Thyroid 12.9 (4.8, 34.7) 6.1 (1.5, 24.7) 9.4 (4.2, 21.1) 0.40 Unknown primary 3.2 (2.1, 4.7) 1.7 (1.0, 2.6) — 0.04 Non-Hodgkin’s lymphoma 1.1 (0.5, 2.2) 0.7 (0.2, 1.7) 0.9 (0.5, 1.6) 0.40 Leukaemia 1.5 (0.9, 2.5) 0.8 (0.3, 2.0) 1.2 (0.8, 1.9) 0.25 * Mortality rate ratio estimated by negative binomial regression. † Mortality rate ratios are reported separately for age groups 0–64 and 65 years and over; the rate ratio for all ages combined is reported only where the P value of an interaction term testing for difference in mortality rate between younger and older age groups was > 0.05. ‡ Not including cervix. na = not applicable because rate ratio was zero (no NT Indigenous deaths from this cancer in 1991–2000).

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

Dx/Rx: lung cancer. Christopher G Azzoli. Massachusetts: Jones and Bartlett, 2006 (viii + 134 pp). ISBN 0 7637 2641 9. This small, single-author American text in pocket-book format provides a succinct but comprehensive overview of lung cancer including its epidemiology, diagnosis and treatment. There are also brief sections on mesothelioma and thymoma. Reflecting the author’s specialty, the content is heavily skewed towards medical oncology. Surgical and radiation oncology aspects are given limited coverage. The style and level of detail suggest that this book would be most useful for medical students and junior hospital doctors, or even lay consumers with some scientific background. The information is presented as dot points — hardly literature, but readable. A brief list of up-to-date key references is provided at the end of each chapter. In general, the information presented is accurate, although there are a few howlers: “Asbestos is ... used as inflammable building material”. “Anyone with a first degree relative with a smoking related cancer should not smoke cigarettes.” It is irritating to see myths perpetuated, such as “carcinoid tumours are highly resistant to chemotherapy and radiotherapy” and “large cell neuroendocrine tumours carry a poor prognosis compared with other types of non-small cell lung cancer”. What is the evidence for these statements? There are good practical hints on the management of complications of lung malignancy (these would be most useful for junior hospital doctors). There is, however, no mention of the use of lasers or stents for the treatment of major airway obstruction. So, in summary, a concise and contemporary overview, but too superficial for the practising clinician managing lung cancer. If the reader requires an evidence-based manual that contains statistics and treatment recommendations more relevant to Australian practice, I would suggest the NHMRC-endorsed Clinical practice guidelines for the prevention, diagnosis and management of lung cancer, recently published by the Australian Cancer Network. David L Ball Chair of Lung Service and Radiation Oncologist, Peter MacCallum Cancer Institute, Melbourne, VIC

David L Ball

When a prominent Australian politician, the then Premier of Tasmania, The Honourable Jim Bacon, publicly announced in February 2004 that he had lung cancer, he was inundated with well-wishing communications sent by post, email and other means. They included 157 items of correspondence recommending a wide variety of complementary and alternative medicines (CAMs). The most common CAMs recommended were meditation, Chinese medicine, “glyconutrients”, juices, Laetrile and various diets and dietary supplements. Although proof of benefit exists or promising preliminary laboratory studies have been carried out for a small number of the recommendations, no scientific evaluation has been performed for most of these treatments. Their potential benefits and harms are not known. Several recommendations were for treatments known to be useless, harmful or fraudulent. Bacon’s experience suggests that cancer patients may receive unsolicited advice to adopt one or more forms of CAM. Both patients and practitioners need access to authoritative evidence-based information about the benefits and dangers of CAMs.

Ray M Lowenthal MD, FRCP, FRACP

Making films from bone marrow aspirates is often a challenge for haematologists and oncologists in training (particularly oncologists). This aspirate taken from a child’s ilium ended up looking more like a femur.

Anthony R Herbert MB BS, BMedSc

Simon D J Gibbs,* John O'Grady,† John F Seymour,‡ H Miles Prince§ * Haematology Registrar, † Dental Oncologist, ‡ Haematoncologist, § Head, Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 8006. simongibbs02ATyahoo.com.au To the Editor: We read with interest the article by Carter and colleagues reporting five cases of jaw osteonecrosis associated with bisphosphonate use.1 To emphasise the association, we report a further eight cases seen at our institution between February 2004 and June 2005. After Marx’s report of the condition in 2003,2 we instituted a policy of active screening for jaw osteonecrosis in patients taking bisphosphonates. Patients were asked about suggestive symptoms, such as tooth pain or dental infection, and underwent oral examination by the treating haematologist or oncologist. Suspected cases were referred to our dental oncology unit. Bisphosphonate therapy was discontinued in established cases to prevent further bisphosphonate accumulation and possible worsening of the complication. Of the eight patients detected with jaw osteonecrosis, five had multiple myeloma, two breast cancer, and one prostate cancer. All were receiving monthly intravenous bisphosphonate therapy: zoledronic acid (4 mg) in seven patients, and pamidronate (90 mg) in the other. Median duration of bisphosphonate therapy before onset of symptoms was 22 months (range, 6–66 months). Five patients were male, and three female. Seven had undergone tooth extraction before presentation (Box), and the five with multiple myeloma had received high-dose corticosteroids. Management was conservative in all eight. No improvement was seen in any patient by 3 months, but, with continued withholding of bisphosphonates, some signs of healing were seen in all by 6 months. Four of the patients had a change in therapy from pamidronate to zoledronic acid (because of the latter’s shorter infusion time) in the 2–18 months before onset of symptoms. None had experienced osteonecrosis while taking pamidronate. It is postulated that zoledronic acid is more often associated with osteonecrosis than pamidronate.3 Appropriate management for patients who need to resume bisphosphonate therapy after osteonecrosis remains to be determined. Clodronate is an orally administered first-generation bisphosphonate which has been used widely in Europe with no reports of associated osteonecrosis.4 Unlike pamidronate and zoledronic acid, it does not contain a nitrogen ring. On this basis, we recently began clodronate therapy in a patient with complete jaw healing after osteonecrosis. Avoiding tooth extractions while taking bisphosphonates should minimise the incidence of osteonecrosis. Our active screening policy allowed earlier detection of osteonecrosis and prompt intervention, including cessation of bisphosphonates and avoidance of debridement of necrotic bone (which often exacerbates the condition), thereby limiting the extent of osteonecrosis. It is uncommon for physicians to ask about dental problems and for dentists to ask about bisphosphonate use. This new complication highlights the need for this to change. Osteononecrosis of the jaw in a patient with multiple myeloma taking zoledronic acid Necrotic maxillary bone and sequestrum formation which developed after tooth extraction. Computed tomography scan showing failure of the bone to heal at the extraction site.

Simon D J Gibbs · John O'Grady · John F Seymour · H Miles Prince