Early changes in PSA and association with outcomes in mCRPC patients.

5063 Background: Declines in prostate specific antigen (PSA) levels at 12-weeks are currently used to evaluate treatments response in metastatic castration resistant prostate cancer (mCRPC). Early PSA fall by 30% at 4-weeks (PSA4w30) has been previously shown to be associated with better outcome in mCRPC in a small single-centre cohort. Methods: We identified mCRPC patients who had received Abiraterone Acetate (AA) between 06.01.06 and 08.09.17 in 13 cancer centres worldwide. Eligible patients had PSA levels assessed at baseline, after 4-weeks and/or 12-weeks of treatment. PSA response was defined as a ≥30% decline from baseline and PSA progression as a ≥25% increase from baseline. Association with overall survival (OS) was analysed using landmark multivariable Cox regression adjusting for previous chemotherapy, including cancer centre as a shared frailty term. Results: We identified 1057 patients who had received AA (447 pre-chemotherapy, 610 post-chemotherapy), with 835 patients having PSA values available at 4 and 12 weeks. Overall, 372/835 (44.5%) had PSA4w30; this associated with longer OS (mOS 22vs15 months; HR = 0.62; 95%CI 0.53–0.72; p < 0.001). A ≥30% PSA decline at 12-weeks (PSA12w30) associated with a lower mortality (mOS 22vs14; HR = 0.57; 95%CI = 0.48–0.67; p < 0.001). Sensitivity analyses confirmed the association between PSA4w30 and OS when pre- and post-chemotherapy cohorts were analysed separately. PSA4w30 strongly correlated with PSA12w30 (ρ = 0.92; p < 0.001). In total, 320/372 (86%) patients with a PSA decline at 4-weeks had a PSA decline at 12-weeks. Conversely, 11/835 (1.3%) patients progressed at 4-weeks and then met the criteria for PSA12w30. PSA4w30 remained correlated with OS (HR = 0.56; 95%CI = 0.48–0.65; p < 0.001) in multivariate analyses including other established prognostic factors in mCRPC (baseline ALP, LDH, Hb, M status and Gleason at diagnosis). Conclusions: PSA changes in the first 4-weeks of AA therapy are strongly associated with clinical outcome in mCRPC patients and should be prospectively evaluated in early treatment switch decision trials.