Association Between Time to PSA Nadir, Radiologic Progression, and PSA Progression in mHSPC Patients Treated with...

Background: Time to prostate-specific antigen (PSA) nadir (TTN) has been proposed as an early indicator of treatment responsiveness in metastatic hormone-sensitive prostate cancer (mHSPC). However, its prognostic relevance in patients treated with next-generation androgen receptor pathway inhibitors (ARPIs), such as abiraterone or enzalutamide, remains incompletely defined. Methods: This retrospective cohort study included 147 patients with mHSPC treated with abiraterone or enzalutamide between 2019 and 2024. TTN, PSA kinetics, radiologic progression-free survival (rPFS), and PSA progression-free survival (PSA-PFS) were analyzed using Kaplan-Meier methods and multivariable Cox regression. TTN was evaluated both as a continuous variable and dichotomized at the cohort median (≤9 vs. >9 months). Results: TTN distributions were comparable between treatment groups (median 9.0 vs. 6.0 months, p = 0.197). Patients with a shorter TTN (≤9 months) experienced significantly longer median rPFS compared with those with longer TTN (>9 months) (10.7 vs. 7.95 months; p = 0.036). No significant association was observed between TTN and PSA-PFS (9.3 vs. 10.75 months; p = 0.34). In multivariable analysis, enzalutamide was independently associated with a reduced risk of radiologic progression compared with abiraterone (HR 0.622; 95% CI 0.441-0.877), whereas TTN was not an independent predictor. Conclusions: A shorter TTN was associated with improved radiologic outcomes, suggesting that rapid PSA suppression may reflect more favorable disease biology in patients receiving ARPI therapy. Although TTN showed limited value in predicting biochemical progression, it may serve as a simple and accessible biomarker for early risk stratification and tailoring follow-up intensity in mHSPC. Validation in larger, multicenter cohorts is warranted.