Prostate Cancer Foundation of New Zealand

To create or enhance an environment to empower men to make informed decisions about the diagnosis and treatment for prostate cancer

Astra Zeneca

Prostate Cancer Screening in Australasia  

Clinical Oncology

Volume 17, Issue 4 , June 2005, Pages 231-233
Prostate Cancer Screening in Australasia
D.S. Lamb*, J.W. Denham?, and B. Delahunt?

*Wellington Cancer Centre, Wellington Hospital, Wellington, New Zealand
Department of Radiation Oncology, Newcastle Mater Misericordiae Hospital, 
New South Wales, Australia
Department of Pathology and Molecular Medicine, Wellington School of 
Medicine and Health Sciences, Wellington South, New Zealand
Received 9 September 2004; revised 14 February 2005; accepted 23 March 
2005. Available online 25 May 2005.

Introduction  ˆ Top

Debate, sometimes highly emotive, continues in Australia and New Zealand about the value of prostate cancer screening. Many epidemiologists and public health physicians have taken the position that, because there is insufficient evidence of benefit to introduce systematic population-based screening (PBS), self-requested screening (SRS) should be actively discouraged. These doctors claim that SRS merely leads to unnecessary treatment of many patients with indolent cancers unlikely to cause health problems in the patient's lifetime. They advocate that patients should only be investigated for prostate cancer when they present with urinary symptoms.

Not surprisingly, governments of Australia and New Zealand are happy to receive such a cost-neutral recommendation, which endorses further periods of inactivity. Unfortunately, however, the recommendation is made on the mistaken belief that prostate cancer causes characteristic urinary symptoms if treatment is required, either when the tumour reaches a certain size or if the tumour is a biologically active one. In fact, prostate cancer is nearly always a silent disease, even when the tumour is locally advanced [1]. Curtailing the practice of SRS would, therefore, inevitably result in the diagnosis of fewer cancers while they were still potentially curable.

We look at the main contentious issues that have caused the debate to polarise in Australia and New Zealand, and make recommendations for resolving these to allow forward progress. The establishment of the Prostate Cancer Risk Management Programme in the UK suggests that some of our problems are generic to other countries, and that we have been slow to address them.

The Prostate Cancer Screening Process  ˆ Top

Measurement of serum prostate-specific antigen (PSA), digital rectal examination (DRE) and prostate biopsy are the basic tools of prostate cancer screening. A PSA value on its own, or even when combined with DRE, has unacceptably low specificity as a screening test for prostate cancer. Raising the threshold for a 'positive' PSA makes the specificity closer to ideal, but at the expense of major loss of sensitivity. Both the sensitivity and specificity of the screening process only become acceptable when prostate biopsies are added to PSA and DRE. This 'two step' screening process is similar to that for breast cancer, in which biopsy of suspicious lesions detected by mammography, clinical examination, or both, is routinely performed.

Can the Prostatic Cancer Screening Process Meet Expectations?  ˆ Top

The requirements for a useful cancer-screening test have been defined by the World Health Organization 2 and 3. The cancer should have a high prevalence in a detectable pre-clinical state, and should be responsible for substantial morbidity and mortality. The testing process should be simple, safe and affordable, as well as having high sensitivity and high specificity. Finally, there should be treatment(s) available that have been demonstrated to lead to improved outcomes when used earlier in the natural history of the cancer.

There is no doubt that prostate cancer does have a high prevalence in a detectable pre-clinical state. Only a quarter to a third of men with prostate cancer present with cancer in an advanced and incurable state [4]. The remainder of the group will have potentially curable disease, and most will not have symptoms, even if the cancer is extensive within the prostate. Only 7% of 800 men, with locally advanced prostate cancer treated in a recently conducted Australasian clinical trial, presented with urinary symptoms causing 'moderate bother' or worse [1].

Some evidence shows that currently available treatments can reduce deaths from prostate cancer when used earlier in the natural history of the disease. The strongest direct support comes from a recent publication on the results of the Scandinavian Prostate Cancer Group study 4 [5]. This was a large, randomised trial comparing radical prostatectomy with watchful waiting in early prostate cancer. At 6.2 years median follow-up, the relative hazard of death from prostate cancer was 0.50 (0.27-0.91), and the relative hazard of distant metastases 0.63 (0.41-0.96) in those patients assigned to radical prostatectomy. Furthermore, indirect evidence supports a link between earlier treatment and a reduced risk of death from prostate cancer. Between 1993 and 1997, the fall in death rates was greater in the USA [6], where screening has been prevalent for many years, compared with the UK [7], where few men are screened on an annual basis. At least part of this difference is likely to be due to screening, which results in more early stage cancers being diagnosed and treated in the USA.

Randomised Clinical Trials on Systematic Population-based
Screening  ˆ Top

So far, only the Quebec trial [8] has published its definitive results. A reduction in the risk of dying from prostate cancer was reported for the screened group, but this conclusion has been heavily challenged because of concerns about the trial design and analysis.

An ongoing randomised trial of biennial PBS on 20,000 Swedish men, which started in 1995, recently reported that cancers detected in the screened group were typically early stage, when curative treatment is usually effective [9]. In addition, there was a clear trend towards down-staging and down-grading on repeat screening, and few symptomatic interval cancers developed in the screened group.

The results of two large ongoing PBS trials, one in the USA [10], and the other in Europe [11], will hopefully shed more light on the value of systematic programmes. Definitive reporting on the European ERSPC trial, which includes the 20 000 Swedish men mentioned above, is expected in 2008.

Current Screening Practices in Australasia  ˆ Top

A recent survey in New Zealand showed that general practitioners had diverse screening practices [12]. Forty-two per cent of doctors were prepared to screen patients up to 79 years of age. This variation is likely to be due to an absence of any applicable recommendations for SRS (ie. screening requested by individuals when there is no PBS programme in place). In August 1996, a joint policy statement was issued by Health Departments in Australia and New Zealand advising against 'routine prostate cancer screening in asymptomatic men' [13]. In 2004, the National Health Committee in New Zealand re-issued its recommendations on prostate cancer screening [14], and the conclusions drawn in that report were similar to those issued in 1996.

We believe that one explanation for policy failing to progress over this 8 year period is the unbalanced composition of governmental advisory bodies. Most of the medical input has been from public health physicians and epidemiologists, with little opportunity for specialists involved in treatment delivery to contribute. As a result, the advisory bodies have only been able to address the issue of systematic PBS, and have not had the collective expertise to make useful recommendations on SRS. The repeated suggestion that widely practised SRS should cease altogether has created confusion and resentment in many middle-aged and older men, as well as the medical practitioners who look after them.

The Way Forward  ˆ Top

Lessons need to be learned from the breast-cancer screening experience. No single clinical trial can be expected to provide all the answers concerning the benefit or otherwise of a screening process. For breast cancer, the benefits of systematic population-based screening were quantified from the results of eight randomised clinical trials involving 500,000 women over a 35-year period [15]. However, even now, debate continues on the age at which screening should commence, and the optimal screening interval for individuals enrolled in the screening programme. 

This debate is reflected in currently different breast-cancer screening practices in Australia and New Zealand. A similar slow accumulation of evidence on the value of systematic PBS for prostate cancer can also be anticipated, and it is likely to be many years before all the present uncertainties have been addressed. Until then, a gradual evolution in screening practices can be expected to occur, rather than a sudden change once a threshold of knowledge has been passed. This means that the polarised 'all or nothing' debate on prostate cancer screening, currently taking place in New Zealand and Australia, is setting unrealistic expectations.

Guidelines for SRS need to be urgently developed and widely distributed in Australia and New Zealand. These guidelines should be readily accessible to the general public, so anomalies in current SRS practice are corrected. First, some men at high risk of prostate cancer are missing the opportunity of early diagnosis and treatment. This is especially relevant to the 10% of cases diagnosed with the disease who have a family history of prostate cancer [16, 17 and 18], as men who have one or more first-degree relatives with prostate cancer have up to 11 times the risk of developing the cancer themselves [18]. Second, and conversely, the existing practice of screening very elderly men makes unrealistic demands on prostate biopsy services, and gives these men expectations, often false, that they will require treatment if a cancer is discovered. For older men, external beam radiotherapy is often the only treatment option, and this is a service in Australasia already under great pressure.

Governments can only make decisions as good as the advice they receive. They need input from independent advisory groups on all aspects of prostate cancer screening. These groups should consist of health professionals experienced in prostate cancer epidemiology, diagnosis and treatment. Patient advocacy bodies should also be represented. As a first step, the advisory groups would develop the SRS guidelines discussed previously, so that scant health resources were targeted on those more likely to benefit. The production of comprehensive educational literature for men with newly diagnosed prostate cancer would also have high priority, to assist them in making informed decisions on the diverse, and sometimes bewildering, management options open to them. At a later date, and as more information becomes available, the advisory groups would recommend when and how systematic PBS could be initiated on selected groups of men. Logically, these are all activities that should be part of national cancer-control programmes that are being implemented, or are already running, in many western countries.

Summary of Recommendations  ˆ Top

(1) Expert advisory committees, consisting of a balance of medical disciplines, and with patient input, should be established. Ideally, they should have reporting channels to national cancer-control programmes; (2) these advisory committees would define the important differences between PBS and SRS, acknowledging the right of the individual to make a 'personal choice' on SRS. To help make this choice, the committees would ensure that men were provided with balanced easy-to-comprehend written information on the screening process, on those most likely to benefit from screening, and on the risks associated with screening. A better informed public should lead to SRS being used more appropriately; (3) the committees would also ensure that men with newly diagnosed prostate cancer were provided with balanced easy-to-comprehend written information on the management alternatives. The decision on which treatment, if any, should not be a lottery dependent on referral patterns; (4) later, as more evidence becomes available, the committees would recommend when and how systematic PBS should be introduced for selected men. Those with genetic risks are likely to be the first to be targeted.

References  ˆ Top

  1. D.S. Lamb, J.W. Denham and H. Mameghan et al., Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer, Radiother Oncol 68 (2003), pp. 255-267.
  2. B.S. Kramer, J.K. Gohagan and P.C. Prorok, Cancer screening: screening and practice, Marcel Dekker Inc., New York (1999).
  3. US Preventative Services Task Force, Guide to clinical preventative services, International Medical Publishing, Alexandria, VA (1996).
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  6. R.T. Greenlee, M.B. Hill-Harmon, T. Murray and M. Thun, Cancer statistics, CA Cancer J Clin 51 (2001), pp. 15-36.
  7. S.E. Oliver, D. Gunnell and J.L. Donovan, Comparison of trends in prostate-cancer mortality in England and Wales and the USA, Lancet 355 (2000), pp. 1788-1789.
  8. F. Labrie, B. Candas and A. Dupont et al., Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial, Prostate 38 (1999), pp. 83-91.
  9. J. Hugosson, G. Aus, H. Lilja, P. Codding and C.G. Pihl, Results of a randomised, population-based study of biennial screening using serum prostate-specific antigen measurement to detect prostate carcinoma, Cancer 100 (2004), pp. 1397-1405.
  10. P.C. Prorok, G.L. Andriole and R.S. Bresalier et al., Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial, Control Clin Trials 21 (2000), pp. 273S-309S.
  11. P.M. Beemsterboear, H.J. de Koning, R. Kranse, P.H. Trienekens, P.J. van der Maas and F.H. Schroder, Prostate specific antigen testing and digital rectal examination before and during a randomized trial of screening for prostate cancer: European randomized study of screening for prostate cancer, Rotterdam, J Urol 164 (2000), pp. 1216-1220.
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