Personalizing the Management of Men with Intermediate-risk Prostate Cancer

Abstract

Prostate-specific antigen (PSA) failure following definitive local therapy for intermediate-risk prostate cancer (PCa) [1] defined as a PSA level >10 but 20 ng/ml, a biopsy Gleason score (GS) 7, or clinical tumor (T) category 2b or 2c is variable, with 5-yr rates ranging from 2% to 70% [2]. Investigators have shown that some of this variation can be explained by considering whether GS 7 is predominately Gleason 4 + 3 [3], whether the percentage of positive biopsies (PPB) is at least 50% versus <50% [4], and whether the patient hasmore than one determinant of intermediaterisk PCa versus a single determinant [5]. In the current issue of the Platinum Journal, Zumsteg and colleagues [6] provide further evidence to substantiate these findings in a population of 1024men treated with high-dose radiation therapy (RT; ie, 81–86.4 Gy) between 1992 and 2007, with 521men (51%) also receiving amedian of 6mo of androgen suppression therapy (AST). Using their results and evidence from prior literature [3–5], they define favorable intermediate-risk (FIR) PCa as thosewith GS 3 + 4 or less and <50%PPB and, atmost, one determinant of intermediate-risk PCa. The remaining men with intermediate-risk PCa are defined as having unfavorable intermediate-risk (UIR) disease. After a median follow-up of 71 mo, the authors found that patientswith UIR PCa had a significant increase in the risk of PSA failure, distant metastasis (DM), and PCaspecific mortality (PCSM) compared with men with FIR PCa; these resultswere found despite amedian of 6mo of AST use in58.5%ofmenwithUIR comparedwith30.1% (p < 0.001) of men with FIR PCa [6]. Stratifying men with intermediate-risk PCa into cohorts of higher risk versus lower risk for PSA recurrence, DM, and PCSM following high-dose RT with or without short-course AST has potential implications for management. Specifically,