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Platinum Priority – Editorial
Referring to the article published on pp. 137–146 of this issue

Screening for Prostate Cancer: Current Status and Future Directions

By: Boris Gershman and R. Jeffrey Karnes

EU Focus, Volume 1 Issue 2, September 2015, Pages 147-148

Published online: 01 September 2015

Abstract Full Text Full Text PDF (152 KB)

Refers to article:

Impact of Early Diagnosis of Prostate Cancer on Survival Outcomes

Roderick C.N. van den Bergh, Stacy Loeb and Monique J. Roobol

Accepted 15 January 2015

September 2015 (Vol. 1, Issue 2, pages 137 - 146)

Population-based prostate-specific antigen (PSA) screening for prostate cancer has become a heated health policy issue in recent years, and a thorough understanding of this complex narrative is essential to ensure progress and innovation as we move forward. In this issue of European Urology Focus, van den Bergh and coauthors [1] present an insightful review of the impact of early diagnosis of prostate cancer via PSA-based screening, and provide both a broader overview of population-based trends in disease characteristics and a nuanced analysis of the two landmark screening trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial [2] and the European Randomized Study of Screening for Prostate Cancer (ERSPC) [3].

As the authors describe, data support both a significant stage migration and a mortality reduction since the introduction of PSA screening in the 1990s. For instance, the proportion of men presenting with metastatic disease has decreased from approximately 1 in 3 in the 1980s to 4% from 2004 to 2010 [1] and [4] and prostate cancer mortality has decreased, with an estimated 45–70% of the decline attributed to screening [5]. Yet despite promising trends in population-based data, the two randomized screening trials have, at first glance, failed to demonstrate the anticipated mortality reduction: PLCO noted no benefit of screening and ERSPC revealed a mortality reduction of 21% over 13-yr follow-up. However, “absence of evidence is not evidence of absence,” and an accurate interpretation of these studies requires a more nuanced analysis. As the authors emphasize, the two studies had significant rates of contamination and noncompliance, both of which would mitigate any screening benefits. As an example, the estimated mortality reduction in ERSPC would increase to as high as 51% after accounting for both effects. Moreover, simulation data support a greater absolute mortality reduction over extended follow-up, with the number needed to treat to prevent one cancer death decreasing from 48 men at 9 yr to 9 men at 25 yr on the basis of ERSPC data [6].

Nonetheless, both leadtime bias and overdiagnosis are real and cannot be overlooked. Estimates vary by study, but overdiganosis may occur in as many as 50% of screen-detected cases [1]. These “harms” of screening, coupled with a smaller than anticipated mortality reduction when applied at a population level, have led to revision of screening guidelines in both the USA and Europe [7] and [8]. The repercussions of such changes can already be seen in clinical practice, with an immediate reduction in PSA screening rates for men of all ages [9]; however, more importantly, the long-term consequences are unknown.

Recognition of the inadequacies of population-based PSA screening represents a critical opportunity for new approaches to screening. To this end, van den Bergh and colleagues appropriately advocate a personalized approach to screening aimed at detecting clinically significant prostate cancer. They describe several potential adjuncts, including risk calculators that combine clinical and laboratory data for more comprehensive risk assessment, multiparametric magnetic resonance imaging for identification of clinically significant disease, and application of genomic data to improve the performance of PSA screening or augment risk stratification.

One additional strategy is to focus on minimizing overtreatment rather than targeting overdiagnosis, as with active surveillance (AS). AS for low-risk prostate cancer has been increasingly adopted since the early 2000s, and long-term follow-up data demonstrate very low disease-specific mortality [10]. Such an approach attempts to strike a balance between reducing treatment-related morbidity and preserving the mortality reduction arising from screening.

Recent events may have signaled the end of indiscriminate, population-wide PSA screening, but they have also accelerated efforts to address the need for reducing prostate cancer mortality while minimizing morbidity associated with screening and treatment. Ultimately, future clinical practice will likely rely on a combination of novel, individualized screening approaches coupled with personalized treatment modalities, both aimed at realizing these goals.

Conflicts of interest

The authors have nothing to disclose.

References

  • [1] R.C. van den Bergh, S. Loeb, M.J. Roobol. Impact of early diagnosis of prostate cancer upon survival outcomes. Eur Urol Focus.. 2015;1:137-146
  • [2] G.L. Andriole, E.D. Crawford, R.L. Grubb III, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319 Crossref
  • [3] F.H. Schroder, J. Hugosson, M.J. Roobol, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328 Crossref
  • [4] I.M. Thompson, J.J. Ernst, M.P. Gangai, C.R. Spence. Adenocarcinoma of the prostate: results of routine urological screening. J Urol. 1984;132:690-692
  • [5] R. Etzioni, A. Tsodikov, A. Mariotto, et al. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control. 2008;19:175-181 Crossref
  • [6] R. Gulati, A.B. Mariotto, S. Chen, J.L. Gore, R. Etzioni. Long-term projections of the harm-benefit trade-off in prostate cancer screening are more favorable than previous short-term estimates. J Clin Epidemiol. 2011;64:1412-1417 Crossref
  • [7] V.A. Moyer. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120-134 Crossref
  • [8] A. Heidenreich, P.J. Bastian, J. Bellmunt, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent—update 2013. Eur Urol. 2014;65:124-137 Crossref
  • [9] S.B. Zeliadt, R.M. Hoffman, R. Etzioni, J.L. Gore, L.G. Kessler, D.W. Lin. Influence of publication of US and European prostate cancer screening trials on PSA testing practices. J Natl Cancer Inst. 2011;103:520-523 Crossref
  • [10] Klotz L, Vesprini D, Sethukavalan P, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. In press. http://dx.doi.org/10.1200/JCO.2014.55.1192

Footnotes

Department of Urology, Mayo Clinic, Rochester, MN, USA

Corresponding author. Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1 507 2669968; Fax: +1 507 2844951.

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