Early PSA Decline Predicts Survival Outcomes in Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors: A Retrospective Single-Center Study

Background and Objectives: Metastatic castration-resistant prostate cancer (mCRPC) remains a clinically heterogeneous condition despite ongoing advances in systemic treatment. Androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate and enzalutamide, have been associated with improved clinical outcomes; however, early identification of patients deriving limited benefit continues to be challenging. Prostate-specific antigen (PSA) kinetics may serve as a practical indicator of treatment response over time. This study aimed to examine the prognostic significance of achieving a ≥50% reduction in PSA levels at three months in patients with mCRPC treated with ARPIs in routine clinical practice. Materials and Methods: In this retrospective single-center study, patients with mCRPC who received abiraterone acetate or enzalutamide between February 2015 and March 2024 were included. Patients were stratified according to PSA decline at three months (≥50% vs. <50%). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Prognostic variables were subsequently examined using univariate and multivariate Cox proportional hazards models. Results: A total of 60 patients were included. At three months, 44 patients (73.3%) achieved a ≥50% decline in PSA levels. Patients reaching this level had longer PFS and OS than those with <50% decline, and the differences between groups were statistically significant. In multivariate analysis, early PSA decline remained significantly associated with improved survival outcomes. Conclusions: A ≥50% decline in PSA levels at three months represents a simple and clinically meaningful indicator of treatment response in patients with mCRPC receiving ARPIs. Early PSA kinetics may assist in timely risk stratification and closer clinical monitoring in routine clinical practice.