Cell cycle progression score differentiates indolent from aggressive prostate cancer in men diagnosed by TURP.

Abstract

e16560 Background: Improved selection of men with localized prostate cancer for conservative management remains a clinical need. We previously showed that the Cell Cycle Progression (CCP) score provides a significant amount of independent prognostic information in men with prostate cancer who opt for conservative management. Here, we extend those results by evaluating the performance of the CCP score in a newly analyzed cohort of conservatively managed men and in a large pooled cohort of men who deferred initial curative therapy. Methods: The CCP score (based on 31 CCP genes and 15 housekeepers) was derived from FFPE tumor sections as previously described. For this study, the CCP score was evaluated in several independent cohorts: 1) a newly studied retrospective cohort from the U.K. diagnosed by a transurethral resection of the prostate (TURP1B, N = 192); 2) a previously studied cohort from the U.K. diagnosed by TURP (TURP1A, N = 200); and 3) two previously studied cohorts from the U.K. diagnosed by needle biopsy (TAPG1, N = 180 and TAPG2, N = 585). The combined cohort included 1,157 conservatively managed men with complete clinical data. Median follow-up for all cohorts was 9.8 years. Hazard ratios (HR) are for a one-unit change in score, and the endpoint for this study was disease specific mortality (DSM). Results: The CCP score was a highly significant predictor of DSM in TURP1B. The univariate HR was 2.96 (95% CI 2.32, 4.04, p = 3.6x10-9), and the multivariate HR after adjusting for CAPRA was 2.27 (95% CI 1.59, 3.23, p = 1.3x10-5). These results are very similar to the HRs obtained in TURP1A cohort, and the test for HR heterogeneity was not significant after adjusting for CAPRA (p = 0.30). In the pooled analyses, the interaction between CCP and cohort was not significant after adjusting for clinical variables. Interestingly, sample type (TURP vs. Needle biopsy) was prognostic even after adjusting for clinical variables. Summaries of the pooled analyses are given in Table. Conclusions: The CCP score adds a significant amount of independent prognostic information for outcome in conservatively managed men. As such, it can be used to help select appropriate patients for deferred treatment regimens like AS or watchful waiting. [Table: see text]