To evaluate the prognostic significance of prostate-specific antigen (PSA) decline depth and duration in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) undergoing abiraterone treatment. We retrospectively analyzed data from 153 high-risk patients with mHSPC receiving first-line abiraterone therapy. Patients were stratified based on PSA dynamics during treatment. Kaplan–Meier survival analysis and Cox proportional hazards regression were used to assess the associations between PSA decline patterns, PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). Among the 153 patients, 85 exhibited PSA nadir <0.2 ng ml−1, 48 had PSA nadir level ranging from 0.2 ng ml−1 to 4 ng ml−1, and 20 presented with a PSA nadir >4 ng ml−1. During abiraterone treatment, PSA nadir <0.2 ng ml−1 was significantly associated with improved median PSA-PFS (51.0 months vs 18.5 months vs 6.9 months, P < 0.0001), median rPFS (52.0 months vs 24.3 months vs 10.3 months, P < 0.0001), and median OS (not reached vs 48.5 months vs 28.1 months, P < 0.0001) compared with PSA nadir ≥0.2 ng ml-1 and <4 ng ml-1, and PSA nadir ≥4 ng ml-1. In the cohort with PSA nadir <0.2 ng ml−1, achieving PSA <0.2 ng ml−1 within 6 months and maintaining this level for over 10 months significantly enhanced clinical outcomes, as evidenced by median PSA-PFS (not reached vs 26.9 months, P < 0.0001), median rPFS (not reached vs 27.5 months, P < 0.0001), and median OS (not reached vs 44.4 months, P < 0.0001). Cox regression analysis revealed that achieving PSA <0.2 ng ml−1 within 6 months post-treatment and sustaining this level for over 10 months are independent prognostic factors. In high-risk patients with mHSPC receiving first-line abiraterone, sustained PSA suppression is a key indicator of therapeutic response. The rate, depth, and duration of PSA decline are critical prognostic factors.

Keywords: dynamics; high-risk; prognostic; prostate cancer; PSA