Early detection of prostate cancer: more information, more clarity.

EUROPEAN UROLOGY 62 (2012) 753–756 available at www.sciencedirect.com journal homepage: www.europeanurology.com Platinum Priority – Editorial and Reply from Authors Referring to the article published on pp. 745–752 of this issue Early Detection of Prostate Cancer: More Information, More Clarity Allison S. Glass, Matthew R. Cooperberg, Peter R. Carroll * Department of Urology, University of California San Francisco, Helen Diller Comprehensive Cancer Center, San Francisco, CA, USA Screening for prostate cancer (PCa) is among the most controversial topics in the field of urology. The outcome of this increasingly strident debate will have considerable impact on the field in developed countries, where the detection and management of PCa constitutes a large portion of what urologists manage. Recently, the US Preventive Services Task Force (USPSTF) finalized a crisp recommendation that routine prostate-specific antigen (PSA)–based screening for PCa be stopped. This recommen- dation won praise from some and strong denunciation by others but left most men wondering what to do. There is truth on both sides of the debate for and against PSA testing. PCa mortality has declined considerably—by 40%—since the advent and widespread uptake of PSA testing in the late 1980s in North America. Large, highly powered, contemporary clinical trials have confirmed the impact of PSA testing in reducing metastasis and cancer-specific mortality [1,2], and projection models have attributed as much as one-half of the observed decline in mortality to PSA screening [3]. However, many overinterpret the absolute impact of this decline for an individual man and fail to acknowledge the considerable, well-documented problems of PCa overdetection and overtreatment. The debate can be resolved only with more granular data and careful interpretation divorced from the emotional positions that can erode the middle ground information all men deserve. The current article by Schro¨der and colleagues [4], a superb group of clinical scientists who have added much to what we know about both the risks and benefits of PSA screening, presents novel and important information about the impact of PSA testing on one very important end point: the risk of metastatic PCa, a harbinger of PCa death in most cases. The authors assessed information available for 76 813 men aged 55–69 yr from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Participants were randomized to either PSA screening every 2–4 yr or usual care. Metastatic (M+) disease was defined by positive lesion on imaging or PSA >100 ng/ml at time of diagnosis (defined as <3 mo after diagnosis) or during follow-up. Assuming that PSA higher than any given threshold denotes M+ disease is debatable, but the value selected is reasonable and is clearly associated with the M+ disease in the majority of cases. Participants’ disease risk was stratified using conventional descriptors. At a median follow-up of 12 yr, the rate ratio of M+ disease in the screening group compared with the control group was 0.70, which translates to a relative risk reduction of 30% and an absolute risk reduction of 3.1 lives saved within 12 yr per 1000 men. These results were based on the primary intent-to-screen analysis; in analysis adjusting for nonscreening in the intervention arm (but not for contami- nation with screening in the control arm), a relative risk reduction of 42% was noted for those men actually screened. Additionally, a 55.6% higher incidence of PCa was found in the screening group. The number needed to invite to screening to avert one case of M+ disease was 328, and the number needed to diagnose (NND) but not necessarily treat was 12. However, this study notably demonstrates that the impact of screening on the risk of M+ disease is primarily seen at or shortly after diagnosis but attenuates during follow-up. The relative risk reduction at diagnosis was 50% but fell to 30% overall after accounting for the follow-up M+ cases. The authors suggested this finding may be due to increasing rates of M+ disease identified in those screened after 7-yr follow-up. In fact, the rate of M+ disease was DOI of original article: http://dx.doi.org/10.1016/j.eururo.2012.05.068 * Corresponding author. Department of Urology, University of California San Francisco, Helen Diller Comprehensive Cancer Center, 1600 Divisadero, San Francisco, CA 94115, USA. Tel. +1 415 353 7098; Fax: +1 415 885 7443. E-mail address: PCarroll@urology.ucsf.edu (P.R. Carroll). 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.