Clinical value of prostate-specific antigen halving time as a predictor of response to first-line systemic treatment for synchronous metastatic castration-sensitive prostate cancer.

BACKGROUND: To address the challenge of early predicting systemic treatment response in metastatic castration-sensitive prostate cancer (mCSPC), this study evaluated the predictive value of prostate-specific antigen halving time (PSAHT) as a biomarker. METHODS: We retrospectively analyzed data for 719 patients with de novo mCSPC, of whom 495 received androgen deprivation therapy alone or combined androgen blockade (the ADT/CAB cohort) and 224 received ADT combined with an androgen receptor signaling inhibitor or docetaxel (the upfront cohort). PSAHT was estimated using log-transformed PSA values at baseline and 1 and 3 months later using a linear mixed-effects model. Individual slopes were used to calculate PSAHT, defined as log(2)/|slope|. Each cohort was divided into short and long PSAHT groups based on the median PSAHT. The primary endpoint was time to castration-resistant prostate cancer (CRPC). A multivariable Cox proportional hazards model was used to assess PSAHT as a predictive biomarker. RESULTS: Log-transformed PSA decreased in a linear manner for up to 3 months post-treatment initiation and then plateaued. Median PSAHT was 0.47 months in the ADT/CAB cohort and 0.41 months in the upfront cohort. CRPC-free survival was more favorable in the short PSAHT group in both cohorts (ADT/CAB, 21.7 months vs. 15.9 months, P = 0.03; upfront, not reached vs. 27.1 months, P < 0.01). In multivariable Cox proportional hazards analysis, PSAHT was associated with time to CRPC in both cohorts. CONCLUSION: PSAHT may have modest prognostic value in de novo mCSPC, although further validation is required.