25th November 2011, Volume 124 Number 1346

Jan J Barendregt

Lamb et al argue for population-wide testing with the PSA test for prostate cancer.1 Their argument is that screening saves lives. However, they ignore the complexities of screening for prostate cancer, and the large potential for doing harm.

Firstly, the evidence for a mortality benefit is weak. It is true that the US PLCO trial was heavily contaminated, possibly beyond repair.2,3 Lamb et al therefore prefer to rely on the European ERSPC and Swedish Gotenburg trials, that both showed a statistically significant mortality benefit.4,5 What they do not mention is that the Gotenburg trial is part of the ERSPC, and when its results are removed from the analysis, the ERSPC mortality benefit is no longer statistically significant.6 So in the end the argument of Lamb et al is based on results from a single trial, that happens to be one with a design that makes it vulnerable to selection bias.6

In addition to this single positive trial result there is some observational evidence that the prostate cancer mortality decline in US and UK may be due to screening, but of course this evidence comes with all the caveats about the confounding that observational studies are subject to.7–9 In all, not a strong case.

Secondly, even if we accept the case for a mortality benefit, Lamb et al completely ignore the elephant in the room. That elephant is called overdiagnosis and overtreatment. Screening leads to overdiagnosis because many tumours detected by screening would never become clinically apparent within the lifetime of the patient, and for prostate cancer the risk of overdiagnosis is clearly large.5,9,10 And overdiagnosis leads to overtreatment because we cannot reliably predict which cancers will progress and which will stay indolent. The side-effects of treatment for prostate cancer are severe.11

Therefore the decision to screen or not cannot be based on the simple argument that it saves lives (even if we accept it does), but it must make the difficult balance between reduced mortality and increased morbidity.

For the Assessing Cost-Effectiveness of Prevention study we did an analysis using the results from the ERSPC trial on mortality reduction and incidence increase.12 We used disability-adjusted life years (DALYs), an outcome measure that combines mortality and morbidity, to evaluate prostate cancer screening. Our results show that screening does indeed decrease prostate cancer mortality, but that in a screened population more disability adjusted life years are lost than in an unscreened one. We therefore concluded that prostate cancer screening is not recommended.

We are not alone. The U.S. Preventive Services Task Force is in the process of revising its previous recommendation for screening of men under 75 years of age to one of not screening at all, based on a similar line of reasoning outlined above: the evidence for mortality benefit is weak, and for harm is strong.13

One would wish the New Zealand men a more serious discussion than the simplistic statement that screening saves lives.

Jan J Barendregt
Associate Professor of Epidemiological Modelling
School of Population Health, University of Queensland
Brisbane, Australia

Author Information

Jan J Barendregt, Associate Professor of Epidemiological Modelling, School of Population Health, University of Queensland, Brisbane, Australia

References

  1. Lamb DS, Delahunt B, Nacey JN. PSA testing in detection and treatment of prostate cancer. New Zealand Medical Journal. 2011;124:13-5.
  2. Andriole GL, Crawford ED, Grubb RL, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009 Mar 26;360(13):1310-9.
  3. Boyle P, Brawley OW. Prostate cancer: current evidence weighs against population screening. CA Cancer J Clin. 2009 Jul-Aug;59(4):220-4.
  4. Hugosson J, Carlsson S, Aus G, et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010 Aug;11(8):725-32.
  5. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009 Mar 26;360(13):1320-8.
  6. Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ. 2010;341:c4543.
  7. Collin SM, Martin RM, Metcalfe C, et al. Prostate-cancer mortality in the USA and UK in 1975-2004: an ecological study. Lancet Oncol. 2008 May;9(5):445-52.
  8. Welch HG, Albertsen PC. Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst. 2009 Oct 7;101(19):1325-9.
  9. Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst. 2010 May 5;102(9):605-13.
  10. Draisma G, Etzioni R, Tsodikov A, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009 Mar 18;101(6):374-83.
  11. Albertsen PC. The unintended burden of increased prostate cancer detection associated with prostate cancer screening and diagnosis. Urology. 2010 Feb;75(2):399-405.
  12. Vos T, Carter R, Barendregt JJ, et al. Assessing Cost-Effectiveness in Prevention (ACE–Prevention): Final Report (http://www.sph.uq.edu.au/bodce-ace-prevention). Brisbane and Melbourne: University of Queensland, Deakin University; 2010.
  13. U.S. Preventive Services Task Force. Screening for prostate cancer: draft recommendation statement. Rockville, MD, October 7, 2011. (http://www.uspreventiveservicestaskforce.org/draftrec3.htm).