Purpose: Metastatic hormone-sensitive prostate cancer (mHSPC) demonstrates heterogeneous treatment responses despite the use of androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPi). Identifying early prognostic indicators is essential to guide treatment monitoring and optimize therapeutic strategies. This study aimed to evaluate clinical characteristics, metastatic burden, and prostate-specific antigen (PSA) kinetics as potential predictors of treatment outcomes in patients with high-risk mHSPC treated with ADT plus ARPi in a real-world clinical setting. Methods: We retrospectively reviewed 51 patients with high-risk de novo mHSPC treated between 2020 and 2024 at a single tertiary center. Patients received continuous ADT plus abiraterone, enzalutamide, or apalutamide for a planned 24 months. Clinical characteristics, PSA kinetics, testosterone levels, and metastatic patterns were analyzed using Kaplan–Meier and Cox regression models. Results: Of 51 patients, 38% completed 24 months without progression (responders), while 62% progressed or died (nonresponders). Responders had significantly fewer nonaxial bone metastases ( P < 0.001) and no visceral disease ( P = 0.044). A PSA nadir ≤0.02 ng/mL was more common among responders (63.2% versus 21.1%, P < 0.01) and independently predicted superior overall survival ( P = 0.001). Enzalutamide use trended toward better progression-free survival (HR: 0.07, P = 0.053). Testosterone levels remained in the castrate range but were higher in responders, likely reflecting pharmacologic differences. Conclusion: In Taiwanese men with high-risk mHSPC, achieving an ultralow PSA nadir and profound PSA decline within 9 months predicted superior outcomes. Metastatic burden—especially nonaxial bone and visceral metastases—remained the strongest adverse prognostic factor. These findings support PSA kinetics as a key risk stratification tool and underscore the need for early treatment intensification in suboptimal responders.
Chiang et al. (Wed,) studied this question.