Platinum Priority – Editorial and Reply from Authors Referring to the article published on pp. 1–7 of this issue Prostate-Specific Antigen–Based Risk Assessment in Younger Men Seth A. Strope, Gerald L. Andriole * Division of Urologic Surgery, Washington University, St. Louis, MO, USA Loeb and colleagues present an interesting and timely review of prostate-specific antigen (PSA) testing in younger men, titled ‘‘Baseline Prostate-Specific Antigen Testing at a Young Age’’ [1]. In the article, younger is defined as 60 yr. Intuitively, it makes sense that PSA may be a better tumor marker in younger men. Serum levels are less likely to be confounded by coexistent benign prostatic hyperplasia, and as has been described in many autopsy series, many such men already harbor small tumors. These features underlie the presumption that younger men with the highest serum PSA values are at highest risk for a later diagnosis of important prostate cancer (PCa). Moreover, compared with older men, younger men have more risk of death from a diagnosis of PCa and the most to gain from treatment. The Scandinavian Prostate Cancer Group-4 study showed an overall benefit for treatment of PCa, but in stratified analysis this benefit was limited to men <65 yr [2]. Despite these considerations, PSA testing has generally occurred in older rather than younger patients. Two recent publications show the magnitude of this disconnect: In a large health system in the northwestern United States, <35% of patients aged 40–54 yr had testing, compared with nearly 50% of patients aged 55–74 yr and 25% of patients aged >75 yr [3]; Drazer et al showed that <45% of men in their 40s and 50s, compared with >45% of men in their 70s, were tested [4]. Moreover, few organizations have advo- cated PSA testing in younger men. While the American Urological Association and the National Comprehensive Cancer Network in the United States now recommend starting discussions about PSA testing in men at the age of 40 yr [5], the European Association of Urology guidelines and others from a variety of primary care organizations do not specify 40 yr as the age at which to start PCa early detection efforts in average-risk men [6]. Such caution stems from concerns about both overdiagnosis of cancers that might not be harmful to patients and the lack of randomized data on which to base recommendations. The three large randomized trials in the literature—the Europe- an Randomized Study of Screening for Prostate Cancer (ERSPC) trial [7]; the Prostate, Lung, Colorectal and Ovary (PLCO) trial [8]; and the Goteborg trial [9]—did not address PSA testing among younger men. In the ERSPC study, the core age range of men was 55–69 yr, with the mean and median age of participants just >60 yr. In the PLCO trial, the age range was 55–74 yr, with nearly 70% of patients >60 yr. In the Goteborg study, the age range of participants was lower than in the ERSPC and PLCO studies, 50–64 yr. The median age at first invitation to screening was 56 yr. None of the studies addressed PSA testing among men <50 yr. Thus, all recommendations about PSA testing in younger age groups rely on observational data. As Loeb and colleagues explain, these observational data are of mixed quality for answering the question of when to offer men PSA testing. Prospective cohort studies in which PCa cases and mortality were ascertained independently of PSA testing provide substantial support for the concept of measuring PSA at younger ages. In these studies, serum from participants was stored, this serum was later checked for PSA levels, and the PCa status of the participants was ascertained based on clinically diagnosed PCa. This pro- spective cohort design eliminates the selection bias that occurs when clinical screening data are analyzed. In contrast, studies in which the serum PSA level has been used to justify the need for, and intensity of, further PSA screening introduce a significant selection bias. Men with higher PSA levels are more likely to continue PSA testing and ultimately are more likely to have a prostate biopsy EUROPEAN UROLOGY 61 (2012) 8–10 available at www.sciencedirect.com journal homepage: www.europeanurology.com DOI of original article: 10.1016/j.eururo.2011.07.067 * Corresponding author. Washington University School of Medicine, Barnes-Jewish Hospital, Siteman Cancer Center, 4960 Children’s Place, Campus Box 8242, St. Louis, MO 63110, USA. Tel. +1 314 362 8212; Fax: +1 314 361 2203. E-mail address: andrioleg@msnotes.wustl.edu (G.L. Andriole). 0302-2838/$ – see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.