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Editorial Prostate Cancer Pearls for Prostate Cancer Screening Monique J Roobol Erasmus University Medical Center, Rotterdam, The Netherlands P rostate cancer screening and its effect on disease-specific mortality has been a topic of debate since the early 1990s. In 2009, after publication of the results of two large randomized prostate cancer screening trials showing contradictory results, the debate continued. Meanwhile, based on the huge amount of data from these two trials it became clear there is no one-size-fits-all for prostate cancer screening. Now, with two recent publications, the debate on whether prostate cancer screening affects mortality can finally be ended. The focus is on how to identify those men that can benefit from screening. Keywords Can PSA be used for early detection? Prostate cancer, screening, PSA, mortality, over diagnosis, biopsy, harm/benefit Since the early 1990s I have been involved in prostate cancer research. In those years one of the key research questions was whether prostate-specific antigen (PSA)-based screening could reduce disease-specific mortality. The first results using the PSA test in combination with a digital rectal examination (DRE) published in 1991 in the New England Journal of Medicine, showed encouraging results. 1 With using the PSA test, applying a cut-off ≥4.0 ng/ml, 33% more prostate cancers were detected with the majority being organ confined, and hence candidates for treatment with curative intent. 1 While this was seen as a positive result, the possibility of over-diagnosis was mentioned. Disclosure: Monique J Roobol has nothing to declare in relation to this article. This article is a short opinion piece and has not been submitted to external peer reviewers. No funding was received for the publication of this article. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: October 2, 2017 Published Online: November 17, 2017 Citation: Oncology & Hematology Review, 2017;13(2):79–80 Corresponding Author: Monique J Roobol, Erasmus University Medical Center, Department of Urology PO Box 2040, 3000 CA Rotterdam, The Netherlands. E: m.roobol@erasmusmc.nl To assess the effect of PSA-based screening on disease specific mortality, a randomized controlled trial (RCT) is the way to go. Both in Europe and the US, RCTs were initiated in 1993. In the US within the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial, 2 and in Europe within the eight-country consortium, the European Randomized study of Screening for Prostate Cancer (ERSPC). 3 Outcome of the randomized controlled trials Trial initiation was followed by a long period of recruitment, randomization, screening, and gathering data on incidence and mortality, in both arms. I was responsible for the Dutch part of ERSPC, randomizing more than 42,000 in the region of Rotterdam. In total the ERSPC included more than 182,000 men. 3 In the US, approximately 76,000 men participated in the so-called P-arm of the PLCO trial. 2 In 2009, both trials published their results on the main outcome, which was prostate cancer-specific mortality. The data had been long awaited. While evidence on the effect on mortality was lacking, use of the PSA test for screening purposes had become more or less standard practice (especially in the US). Both trails showed contradictory results which unfortunately caused even more uncertainty. The ERSPC trial showed that with repeat PSA-based screening in men aged 55–69 years, at time of inclusion, prostate cancer specific mortality was reduced by 20%, as compared with no, or very low, rates of opportunistic PSA testing. 4 The PLCO trial concluded that there was no effect on prostate cancer specific mortality. 5 The conflicting outcomes of the ERSPC and PLCO trials resulted in a lot of debate on which one was to be believed, and which one not. I felt this to be a loss since we could learn a lot from the huge amount of data the two trails generated. The following observations became clear from both trials: that an elevated PSA test should never directly trigger a prostate biopsy; very low PSA levels (i.e., <1.0 ng/ml) in men within this age group of 55–70 years should result in retesting after a long interval (e.g., >5 years) or even in no further testing; and that men who started screening at age >70 are more likely to experience more harm than benefit. In addition, the data showed that the rate of metastatic TOU CH MED ICA L MEDIA 79