Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis

Declines in prostate-specific antigen (PSA) levels at 12wk are used to evaluate treatment response in metastatic castration-resistant prostate cancer (mCRPC). PSA fall by ≥30% at 4wk (PSA4w30) has been reported to be associated with better outcome in a single-centre cohort study. To evaluate clinical relevance of early PSA decline in mCRPC patients treated with next-generation hormonal treatments (NGHTs) such as abiraterone and enzalutamide. This was a retrospective multicentre analysis. Eligible patients received NGHT for mCRPC between 6 January 2006 and 31 December 2017 in 13 cancer centres worldwide, and had PSA levels assessed at baseline and at 4 and/or 12wk after treatment. PSA response was defined as a ≥30% decline (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. We identified 1358 mCRPC patients treated with first-line NGHT (1133 had PSA available at 4wk, and 948 at both 4 and 12wk). Overall, 583 (52%) had a PSA4w30; it was associated with longer OS (median: 23; 95% confidence interval [CI]: 21–25) compared with no change (median: 17; 95% CI: 15–18) and progression (median: 13; 95% CI: 10–15). A PSA12w30 was associated with lower mortality (median OS 22 vs 14; hazard ratio=0.57; 95% CI=0.48–0.67; p