Early prostate specific antigen response and overall survival in metastatic hormone sensitive prostate cancer: Real-world data on age, body mass index, and treatment.

Abstract

109 Background: Prostate-specific antigen (PSA) response is a strong prognostic marker for overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC), as shown in prospective trials. A rapid, deep PSA drop (≤0.2 ng/mL within 6 months) is linked to improved survival, but real-world evidence remains limited. This study examines real-world patterns of early PSA response and its prognostic significance in mHSPC, considering age, body mass index (BMI), and treatment. Methods: Retrospective cohort study of 5,048 U.S. Veterans with mHSPC using Veterans Health Administration data between 2017–2024. Early PSA response was defined as PSA ≤0.2 ng/mL at 6–12 months. OS and PSA response heterogeneity were analyzed by age, BMI, and treatment type (androgen deprivation therapy (ADT) alone, ADT+docetaxel, or ADT+androgen receptor pathway inhibitor (ARPI)). Kaplan–Meier and Cox proportional hazards models evaluated OS while chi-squared tests compared clinical characteristics. Results: Of 5,048 veterans with mHSPC, 2,572 received ADT monotherapy, 511 received ADT+docetaxel, and 1,961 received ADT+ARPI. PSA ≤0.2 ng/mL at 6–12 months was achieved in 30% of patients on ADT monotherapy, 36% with docetaxel-based therapy, and 53% on ADT+ARPI (p<0.001). Higher BMI was associated with greater PSA response rates—29% for BMI<25, 42% for BMI 25–29.9, and 47% for BMI≥30 (p = 0.001). No consistent trend was observed between age and PSA response. Kaplan–Meier analysis demonstrated improved OS for patients achieving PSA ≤ 0.2 ng/mL, regardless of age, BMI, or treatment group. Median survival (MS) by early PSA response was as follows: for PSA ≤0.2 ng/mL (n=1,982), MS was not reached due to >50% survival at 60 months; for PSA 0.2–2 ng/mL (n=1,302), MS was 52 months (ADT), 45 months (ADT+docetaxel), and 44.5 months (ARPI); for PSA 2–10 ng/mL (n=808), MS was 30 months (ADT), 32 months (ADT+docetaxel), and 25 months (ARPI); and for PSA >10 ng/mL (n=952), MS was 20 months (ADT), 22 months (ADT+docetaxel), and 16 months (ARPI). Conclusions: PSA decline to ≤0.2 ng/mL at 6–12 months was a strong predictor of OS regardless of treatment. Combination therapy with ADT+ARPI led to a more robust PSA response rates and better survival. These real-world results are consistent with clinical trial evidence, further supporting the prognostic value of early PSA kinetics as a surrogate marker for survival and clinical outcomes. Hazard model. PSA Threshold Categories Median Survival (months) Adjusted HR* 95% CI P-Value ≤0.2 NR* ref -- -- -- >0.2 to 2.0 48 1.95 1.75 2.17 <0.001 2.0 to 10 29 3.24 2.89 3.63 <0.001 10+ 19 5.76 5.17 6.42 <0.001 *NR = not reached; HR = hazard ratio.