Association between early PSA increase and clinical outcome in patients treated with enzalutamide for metastatic castration resistant prostate cancer.

Abstract

231 Background: Prostate specific antigen (PSA) decline by 50% from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration resistant prostate cancer (mCRPC). However, in clinical practice, PSA changes are monitored monthly in several centers. We evaluated the association between PSA changes at 4 weeks and clinical outcome. Methods: We retrospectively evaluated mCRPC patients treated with enzalutamide after docetaxel. Early PSA increase was defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥ 30% (PSA30w4) and ≥ 50% (PSA50w4) from baseline.Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Interval (95% CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed including the following variables: PSA+20w4, PSA30w4, PSA50w4 and PSA50w12, baseline PSA, performance status, LDH values, sites of metastases, age. Results: We assessed 193 patients with median age of 73.1 years (range, 42.8 to 90.7). The median follow-up was 11.7 months. PSA+20w4 was associated with shorter PFS (median PFS 2.0 vs. 6.1 months; HR 4.03; 95% CI 2.62-6.19; p < 0.0001) and shorter OS (median OS 5.9 vs. 15.6 months; HR 3.48; 95% CI 2.12-5.69; p < 0.0001). At multivariate analysis, PSA+20w4 remained predictive of both PFS and OS [HR 4.03 (95% CI 0.2.62-6.19; p < 0.0001) and HR 3.48 (95% CI 2.12-5.69; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95% CI 0.21-0.67; p = 0.0009) and HR 0.34 (95% CI 0.19-0.60; p = 0.0003), respectively]. No cases of PSA flare were reported. Conclusions: An early PSA increase, defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4), could be useful to identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA+20W4 as an early and cheap biomarker of primary resistance to enzalutamide.