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A European Model for an Organised Risk-stratified Early Detection Programme for Prostate Cancer - Beyond the Abstract

Despite the proven benefit of prostate cancer screening by the European Randomized Study of Screening for Prostate Cancer (ERSPC),1 policymakers do not recommend prostate cancer screening because of its related overdiagnosis: a fair point when it comes to a purely PSA-based screening algorithm as was applied within the ERSPC. However, the use of PSA, as the only selection tool for prostate biopsy, resulting in substantial overdiagnosis, is long out of date, and with it the argument of overdiagnosis to plea against prostate cancer screening. The latest considerations of the European Council on screening date from 2003 and did not support a programme for prostate cancer.2 Since those last eighteen years, and actually already three decades after the ERSPC started, new technologies have emerged such as multivariable prediction models (i.e. risk calculators) and magnetic resonance imaging (MRI). These tools build on the successes and failures of PSA. Also since the recommendations against prostate cancer screening, the incidence of advanced and metastatic prostate cancer continues to increase.3,4

Public awareness of this risk of developing a potentially lethal form of prostate cancer without the existence of an organised early detection program paves the way for opportunistic screening. This unstructured way of screening does not reduce the prostate cancer-specific mortality rate and is associated with even more overdiagnosis.5 Therefore, the time has come to reconsider an early detection strategy for prostate cancer that combines the proven benefits of PSA testing and at the same time, limits overdiagnosis through the use of new risk stratification tools.

To support this reconsideration, our review provides an overview of these new risk stratification tools and the subsequent expected benefits and pitfalls and takes into account the differences in resource availability throughout Europe. The most important principle of the presented early detection strategy is that the direct link between PSA and immediate biopsy is broken. This can already be done by, for example, the use of PSA density as a simple, inexpensive, but strong predictor. Further refinement of the risk stratification pathway can be performed with e.g., often freely available, well-calibrated risk calculators and/or the use of the MRI.

Most results in this review derive from clinical cohorts and not all are supported by the highest level of evidence. This is reflected by the only weak recommendation of the EAU guidelines for a risk-stratified strategy for early detection of prostate cancer.6  However, available literature provides valuable, indirect evidence which all points towards a better balance between the harms and benefits of early detection of prostate cancer compared to the classic PSA-based screening method. Moreover, several screening trials are underway that do incorporate the new tools and are listed in the supplementary table of this review. Meanwhile, we are delighted with the first positive results of the STHLM3-MRI trial on the performance of these new tools in a screening population.7,8  Although much longer follow-up is needed to determine the effect on metastatic rates and prostate cancer-specific mortality, this trial confirms the improvements to the PSA-only-based screening method in terms of limiting overdiagnosis while maintaining or even improving the detection of potentially lethal prostate cancer. This will positively influence the strength rating into a ‘strong’ recommendation of the EAU guidelines to offer an individualised risk-adapted strategy for the early detection of prostate cancer.

Awaiting the reconsiderations of the European Commission policymakers, the algorithm discussed in our review can serve as guidance in current daily clinical practice to stop the increasing rate of advanced prostate cancers and to minimize the deleterious effects of the ongoing opportunistic screening practices.

Written by: Renée Hogenhout,1 Hein Van Poppel,2 Monique J. Roobol1

  1. Department of Urology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
  2. Department of Development and Regeneration, University Hospital KU Leuven, Belgium

References:

  1. Schröder, F. H. et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360, 1320-1328 (2009).
  2. The council of the European Union. Council recommendation of 2 December 2003 on cancer screening (2003/878/EC). Official Journal of the European Union L327, 34-38 (2003).
  3. Jemal, A., Culp, M. B., Ma, J., Islami, F. & Fedewa, S. A. Prostate Cancer Incidence 5 Years After US Preventive Services Task Force Recommendations Against Screening. J Natl Cancer Inst 113, 64-71 (2021).
  4. Lenzen-Schulte, M. Prostatakrebs-Screening: Prüffall PSA-Test. Dtsch Arztebl 117, 1-2 (2020).
  5. Arnsrud Godtman, R., Holmberg, E., Lilja, H., Stranne, J. & Hugosson, J. Opportunistic testing versus organized prostate-specific antigen screening: outcome after 18 years in the Göteborg randomized population-based prostate cancer screening trial. Eur Urol 68, 354-360 (2015).
  6. Mottet, N. et al. (EAU Guidelines Office, Arnhem, The Netherlands, 2021).
  7. Eklund, M. et al. MRI-Targeted or Standard Biopsy in Prostate Cancer Screening. N Engl J Med (2021).
  8. Nordström, T. et al. Prostate cancer screening using a combination of risk-prediction, MRI, and targeted prostate biopsies (STHLM3-MRI): a prospective, population-based, randomised, open-label, non-inferiority trial. Lancet Oncol (2021).

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