Prognostic role of early PSA drop in castration resistant prostate cancer patients treated with abiraterone acetate or enzalutamide.

BACKGROUND: Previous studies demonstrated a predictive value of prostate-specific antigen (PSA) kinetics for treatment outcome. Our retrospective study evaluates the prognostic role of early PSA drop in metastatic castration resistant prostate cancer (mCRPC) patients receiving abiraterone acetate (AA) or enzalutamide (E). METHODS: All mCRPC patients treated with AA or E at the San Luigi Hospital in Orbassano between 2010 and 2018 and at the Ordine Mauriziano Hospital in Turin between 2014 and 2018 were included in this retrospective study. Only patients with an early PSA (measured 28-60 days after the beginning of the treatment) were included in the analysis. Patients were divided in early responders and non-early responders according to early PSA response (drop >/= 50% from baseline). Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were performed. RESULTS: Of 144 patients with early PSA value, 61 (42.4%) patients received E (docetaxel-naive 42, post-docetaxel 19) and 83 (57.6%) received AA (docetaxel-naive 44, post-docetaxel 39). 75 (52.1%) patients achieved early PSA drop. In docetaxel-naive setting (n=86), median PFS was 14.9 (with early PSA drop) vs 8.8 months (without early PSA drop, p=0.001). In post-docetaxel setting (n=58) median PFS was 11.9 vs 4.5 months (p<0.001). Globally, median PFS was 14.9 vs 6.3 months in patients with and without early PSA drop, respectively (p<0.001). In docetaxel-naive setting, patients with early PSA drop had a median OS of 39.5 vs 18.8 months (p=0.12). In post- docetaxel setting median OS was 29.6 vs 10.7 months (p=0.01). Comprehensively, median OS was 31.9 vs 16.3 (p=0.002) in patients with and without early PSA drop, respectively. At multivariate analysis, early PSA drop confirmed an independent association with PFS (HR 0.21; 95%CI: 0.12- 0.38, p<0.001) and OS (HR 0.25; 95%CI: 0.12-0.50, p<0.001). CONCLUSIONS: mCRPC patients treated with AA or E, in docetaxel-naive or post-docetaxel setting, with early PSA drop had significantly better OS and PFS.