PSA Response as a Prognostic Factor of Overall Survival in Patients with Metastatic Hormone-sensitive Prostate Cancer Treated with Apalutamide: Real-world Evidence.

Background and objective: Prostate-specific antigen (PSA) decline has been proposed as a prognostic marker in metastatic hormone-sensitive prostate cancer (mHSPC). We aimed to evaluate whether a ≥90% PSA decline (PSA 90) predicts overall survival (OS) in patients treated with apalutamide plus androgen deprivation therapy (ADT) in real-world practice. Design, setting, and participants; Intervention (include if there are any). Outcome measurements and statistical analysis: We conducted a multicenter retrospective study including patients with mHSPC treated with apalutamide plus ADT in 17 hospitals. PSA 90 was defined as a ≥90% decline from baseline within 3 or 6 mo or PSA <0.02 ng/ml. To evaluate the effect of PSA response, a landmark analysis was performed at 3 and 6 mo. We evaluated OS and radiographic progression-free survival (rPFS). Multivariable Cox regression analyses were adjusted for age, baseline PSA, disease presentation (de novo vs recurrent), volume (CHAARTED), and risk (LATITUDE). Results and limitations: Between May 2018 and September 2024, 1022 patients with mHSPC were included in the Real-World Evidence APA database. The median age was 68.5 yr (interquartile range [IQR] 62.7-74.6) and baseline PSA 8.2 ng/ml (IQR 1.8-41.1). At 3 mo, 807 patients (87%) achieved a PSA 90 response; at 6 mo, 773 patients (88%) were PSS 90 responders. PSA 90 response at 3 and 6 mo was associated with a statistically significant lower hazard of OS (hazard ratio [HR] = 0.31, 95% confidence interval [CI] = 0.19-0.51). Similar results were observed for PSA 90 at 6 mo (HR = 0.29, 95% CI = 0.17-0.48). PSA 90 response at 3 and 6 mo was also associated with a statistically significant lower hazard of rPFS response (HR = 0.46, 95% CI = 0.31-0.69, and HR = 0.41, 95% CI = 0.26-0.63, respectively). Limitations include the retrospective design, potential selection bias, incomplete PSA measurements, heterogeneity in imaging, and shorter follow-up, which may affect the precision and generalizability of our findings. Conclusions: PSA 90 response at 3 and 6 months is a strong prognostic marker for overall survival and radiographic progression-free survival in patients with metastatic hormone-sensitive prostate cancer treated with apalutamide. These findings support PSA 90 as an early prognostic indicator for clinical risk stratification. Patient summary: We studied how blood levels of PSA change in men with advanced prostate cancer treated with apalutamide. Patients whose PSA dropped by 90% or became undetectable within 3 or 6 mo lived longer, suggesting that early PSA reduction can help predict better outcomes.