4th November 2011, Volume 124 Number 1345

David S Lamb, Brett Delahunt, John N Nacey

After 2 years of deliberation, the Parliamentary Select Committee investigating the early detection and treatment of prostate cancer released its report on 27 July 2011.The report encourages New Zealand men to seek up-to-date evidence-based information from their general practitioners about the advantages and disadvantages of screening for prostate cancer. The report also recommends that general practitioners routinely provide this information as part of the cardiovascular risk assessment performed on men aged 45 years. For men with known genetic risk factors for prostate cancer, the recommendation was that testing should be offered at an earlier age.

At first glance, the report might be taken as a simple statement defining the status quo, but this is not the case. Currently, only about 40% of the New Zealand male population over the age of the age of 50 years undergo regular prostate-specific antigen (PSA) testing for prostate cancer, which means that well over half of the male population is notbeing tested. This is a point of concern for two reasons; firstly, the Austrian Tyrol study suggests that the coverageof a PSA testing programme is more important for achieving population survival benefits than the intensityof the PSA testing.

The Austrian Tyrol study showed that testing of 86% of the population, many with a single PSA test, reduced prostate cancer mortality by 56%.2 Secondly, data from New Zealand and Australia suggest that tested and untested groups of men have large ethnic and regional differences, indicating there are significant inequalities introduced by poor coverage. Māori men are tested less often than non-Māori,3and men who reside in country areas are tested less often than men who live in urban centres.4

The Select Committee report is now recommending that the key information on PSA testing should be provided to all men, so equitability is restored, and every man is able to make an informed decision on whether or not he wishes to be tested. The Select Committee is to be congratulated on their interpretation of the apparently conflicting results of the PSA-based screening trials reported to date. There are three basic requirements for a trial result to have any credibility.

Firstly, the randomisation process needs to be properly balanced, so that men in the screened arm should match those in the control arm. This was a fault of the Quebec trial5 which was the first to report survival advantages for PSA-based screening.

Secondly, the follow up of men on screening trials for prostate cancer must extend over many years for a potential difference to be demonstrated. This is because the lead time from diagnosis by PSA based screening is 6–12 years.6 The European Randomised Study of Screening for Prostate Cancer (ERSPC) was therefore designed to report as soon as a prostate cancer survival advantage of 20% was detected in the screened arm, which occurred after a median follow up of nine years.7 The Göteborg randomised trial demonstrated that the survival advantage had increased to 40% by 14 years median follow up, and projections showed that the advantage was still increasing at that time.8

Thirdly, any randomised screening trial cannot draw from a population where PSA testing has already become common practice. This was a major fault in The Prostate, Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) which reported no apparent survival benefit from screening, with a median follow up of 11.5 years.9 However, the reason for this result was that in the three years prior to participation in the PLCO trial, 44% of men had had at least one PSA test, and by the sixth year of follow up, 52% of men on the control armhad had at least one PSA test after enrolling on the trial. Such contamination of the trial population reduces differences in PSA testing practices between the control and screened arms, and makes the result of the PLCO trial ‘inconclusive’ rather than ‘negative’.

Once the flawed screening trials are removed from the equation, only the ERSPC and Göteborg trials remain, and the results of these trials give a consistent message. PSA testing does save lives,10 and the number of lives saved increases as the time interval from the commencement of PSA testing becomes longer. This means that younger men are more likely to achieve a survival benefit from the early diagnosis and treatment of their prostate cancer than older men, due to an increased mortality from unrelated causes in the older age group.

The question will now be asked as to whether or not the survival advantages are large enough to justify the effort and the costs to the health services resulting from additional PSA testing. In addition to this the (albeit small) risks to men associated with prostatic biopsy need to be factored in. Of the approximately 600 men who die of prostate cancer each year in New Zealand, we estimate that about 400 will initially present with metastatic disease.

PSA testing has been shown to reduce the likelihood of presenting with metastases by 50 percent,11 and as a consequence PSA testing has the potential to save up to 200 lives each year. Ultimately it is the decision of individual men to determine whether or not they agree with us and elect to be tested, just as every man has the right to decide whether or not the risks of the disease outweigh the risks of treatment, after prostate cancer is diagnosed.

Author Information

David Lamb, Associate Professor, Department of Pathology and Molecular Medicine, University of Otago, Wellington; Brett Delahunt, Professor, Department of Pathology and Molecular Medicine, University of Otago, Wellington; John N Nacey, Professor, Department of Surgery and Anaesthesia, University of Otago, Wellington.

Correspondence

Associate Professor David Lamb, Department of Pathology and Molecular Medicine, University of Otago, PO Box 7343, Wellington South 6242, New Zealand.

Correspondence Email

david.lamb@otago.ac.nz

Competing Interests

None.

References

  1. Parliamentary Select Committee Report on the early detection and treatment of prostate cancer. Released 27 July 2011
  2. Oberaigner W, Horninger W, Klocker H, et al. Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing. Am J Epidemiol 2006;164:376-384. http://aje.oxfordjournals.org/content/164/4/376.long
  3. Lamb DS, Bupha-Intr O, Bethwaite P, et al. Prostate Cancer – are ethnic minorities disadvantaged? Anticancer Res 2008;28:3891-3896.
  4. Coory MD, Baade PD. Urban-rural differences in prostate cancer mortality, radical prostatectomy and prostate-specific antigen testing in Australia. Med J Aust 2005;182:112-115.
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  7. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomised European study. N Engl J Med 2009;360:1320-1328.
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  10. National Cancer Institute bulletin 13 July 2010. PSA screening substantially improves cancer-specific survival without the extent of over-diagnosis and treatment. National Cancer Institute: Bethesda, MD 20892-8322.
  11. Aus G, Bergdahl S, Lodding P, et al. Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer – results from a prospective, population-based randomized controlled trial. Eur Urol 2007;51:659-664.