A Risk-Stratified Approach to Prostate-Specific Antigen Screening

Abstract

Ever since the measurement of prostate-specific antigen (PSA) was proposed for the detection of prostate cancer (PCa) in the mid-1980s, PSA screening has been controversial. Initial results of PSA screening trials conflicted. A large US study showed no effect of PSA screening on PCa-specific mortality, although >50% of men in the control arm received screening, minimizing the ability to detect a benefit of screening [1]. However, approximately a 20% decrease in PCa-specific mortality was seen in the screened arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) [2]. Continued follow-up of the ERSPC cohort showed even better results with an approximate 30% reduction in PCa-specific mortality [3]. Most recently, a secondary analysis of the US data (Prostate, Lung, Colorectal, and Ovary cancer screening study) showed a survival benefit in men with minor to no comorbidities [4]. Thus, although data from both Europe and the United States now show that screening in appropriately selected men can reduce PCa-specific mortality, there is no doubt that screening results in overdiagnosis and overtreatment for many men. Contemporary data from the United States suggest that most men (approximately 90%) receiving a PCa diagnosis will receive active treatment [5]. Of the men with a known treatment course in ERSPC, 81.5% received active treatment [2]. Unfortunately, all current PCa treatments are associated with risks for morbidity and complications, which has led many clinicians and public health policymakers to conclude that the risks of screening may outweigh the benefits. Given that we now know that PSA-based screening can reduce PCa-specific mortality, the next step is to better understand which groups of men need screening, which can safely not be screened (or perhaps screened just once), and the optimal interval of screening. In other words, we need to better understand how to risk stratify our approach to PCa screening. To begin to address these issues, Bul et al examined the intermediate term outcomes (approximately 15 yr) from a cohort of ‘‘low’’-risk men [6]. The current report by Bul et al describes the outcome of men 55–74 yr of age who had a single PSA 150 times more likely to die of causes other than PCa than they were to die of PCa. They were also 10–11 times less likely to die of PCa than men with a baseline PSA >3 ng/ml. The percentages of men who died of PCa in the 2–2.9 ng/ml, 1–2 ng/ml, and 1 ng/ml) versus low risk (1 ng/ml) group. In contrast, the European Association of Urology (EAU) recommends a PSA at age 40. Further