Early Achievement of Ultra-low PSA Levels Correlates With Prolonged Radiologic Progression-free Survival (rPFS) in Metastatic Hormone-sensitive Prostate Cancer (mHSPC).

BACKGROUND: Ultrasensitive assays enable detection of prostate-specific antigen (PSA) levels below 0.2 ng/mL, previously considered undetectable, allowing a more refined assessment of treatment response in metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the association between early achievement of ultra-low PSA levels and radiographic progression-free survival (rPFS). MATERIALS AND METHODS: Patients received first-line androgen deprivation therapy (ADT) alone, ADT plus docetaxel, or ADT combined with androgen receptor pathway inhibitors (ARPIs). PSA levels were measured at baseline and during the first 3 months. Patients were stratified according to the lowest PSA level achieved within 3 months: < 0.02 ng/mL, 0.02 to 0.2 ng/mL, and > 0.2 ng/mL. rPFS was estimated using the Kaplan-Meier method. RESULTS: Of 347 patients, 323 were included in the analysis. Median age was 68 years, and 51.7% had ECOG performance status 0. High-volume disease was present in 50.5%, and 76.5% had synchronous metastases. Treatment included ADT alone (25.1%), ADT plus docetaxel (24.5%), and ARPI-based therapy (50.5%). Within 3 months, 15.5% achieved PSA < 0.02 ng/mL, 18.9% had PSA 0.02 to 0.2 ng/mL, and 65.6% had PSA > 0.2 ng/mL. Ultra-low PSA responses were more frequent with ARPI-based therapy (20.9%) compared with ADT alone (12.4%) and ADT plus docetaxel (7.6%). Median rPFS was 34.2 months (95% confidence interval, 27-40). Five-year rPFS rates were 89%, 80%, and 18% for PSA < 0.02, 0.02 to 0.2, and ≥ 0.2 ng/mL, respectively (P < .001). CONCLUSION: Early achievement of ultra-low PSA (< 0.02 ng/mL within 3 months) is strongly associated with prolonged rPFS in mHSPC and may serve as a novel early surrogate marker of treatment efficacy.