Predictive Role of PSA Kinetics in Oncological Outcomes of Metastatic Castration-sensitive Prostate Cancer

Background/Aim: Oncological outcomes for metastatic castration-sensitive prostate cancer (mCSPC) have improved with upfront androgen receptor signaling inhibitor (ARSI) doublet therapy. However, the prognostic value of prostatespecific antigen (PSA) kinetics in real-world settings remains unclear. This study aimed to evaluate the clinical significance of PSA kinetics in patients with high-risk mCSPC. Patients and Methods: We retrospectively analyzed 352 patients with high-risk mCSPC from the ULTRA-J database who received upfront ARSI doublet therapy between 2018 and 2023. PSA kinetics, including PSA nadir, PSA response rate, and time to PSA nadir (TTN), were assessed. Associations with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards models. Results: A PSA nadir <0.02 ng/ml and PSA response rate >99% were significantly associated with prolonged CRPC-FS and OS (p <0.05). Conversely, TTN <3 months was associated with poorer outcomes. Multivariate analysis identified PSA nadir >0.02 ng/ml, PSA response rate <99%, and TTN <3 months as independent predictors of shorter CRPC-FS and OS. These trends were generally consistent across ARSI agents, although some differences were observed in subgroup analyses. Conclusion: PSA kinetics are strong independent prognostic factors in patients with high-risk mCSPC treated with upfront ARSI doublet therapy. These readily available biomarkers may help identify patients who require treatment intensification or closer monitoring in clinical practice.