A post hoc analysis of radiographic progression with nonrising prostate-specific antigen in patients with metastatic castration-resistant prostate cancer (mCRPC) in the PREVAIL study

Abstract

Background: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple pathways. Prostate-specific antigen (PSA) level is the most widely used parameter for disease monitoring, but it has well-recognized limitations including discordant results when compared with imaging studies.We performed the first systematic quantification of patients ( pts) with nonrising PSA (nrPSA) at radiographic progression (RP) while on enzalutamide in the multinational, randomized controlled PREVAIL study. Methods: Chemotherapy-naïve men (n = 872) with mCRPC treated with enzalutamide were analyzed post hoc to identify those with rising PSA (rPSA) versus nrPSA (ie, >1.05 vs ≤1.05 times the PSA level from 3 months earlier) at the time of RP. Pts received oral enzalutamide 160 mg/day plus androgen deprivation therapy. Clinical characteristics and disease outcomes, including the main outcome measures of progression-free survival (PFS) and overall survival (OS), were compared between the rPSA and nrPSA groups. Results: Of 265 PREVAIL pts with RP and evaluable PSA levels in the enzalutamide arm, 19% had an nrPSA. Baseline clinical characteristics of the 2 groups were similar. Median PFS in the nrPSA group was 8.3 months vs 11.1 months in the rPSA group (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.26-2.23). Overall survival was similar between the 2 groups (not yet reached vs 32.4 months; HR, 0.68; 95% CI, 0.37-1.26). Notably, in pts who had bone-only disease at study entry, 40.3% (31/77) developed soft-tissue disease at progression. Conclusions: Nonrising PSA at RP is a common phenomenon in pts with mCRPC treated with enzalutamide, but its influence on OS is indeterminate. The high rate of development of new soft tissue disease in pts without prior measurable disease is also notable. It is important to use surveillance imaging rather than relying on PSA alone to monitor pts with mCRPC. Whether nrPSA progression represents a genotypically distinct process with implications for clinical decision-making remains speculative.