Comprehensive Evaluation of Androgen Receptor Pathway Inhibitors in Metastatic Castration-Sensitive Prostate Cancer: A Multicenter Inverse Probability of Treatment Weighting-Based Study.

INTRODUCTION

Androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) is a guideline-endorsed standard for metastatic castration-sensitive prostate cancer (mCSPC). Robust comparative data on individual ARPIs and their subsequent management after castration resistance remain limited.

METHODS

This multicenter retrospective study included consecutive patients who received first-line ARPI for mCSPC between January 2018 and December 2023. Inverse probability of treatment weighting (IPTW) balanced the baseline clinicopathological variables across the abiraterone (n = 136), enzalutamide (n = 80), and apalutamide (n = 58) cohorts. PSA response subgroups were defined as early response (PSA <0.2 ng/mL by 3 months and sustained for 12 months), delayed response (first attainment ≥6 months, sustained for 12 months), early relapse (attainment but rebound ≥0.2 ng/mL within 12 months), and nonresponse (no attainment).

RESULTS

Among 274 evaluable male patients, apalutamide yielded more grade ≥2 toxicities and dose modifications, although grade ≥3 events were comparable across arms. After IPTW, time to castration-resistant prostate cancer (CRPC) and overall survival (OS) did not differ among the ARPIs (P = .657, P = .286), and PSA ≤0.2 ng/mL conversion rates at 1, 3, 6, and 12 months were similar. Patients with early and delayed responses showed equivalent times to CRPC, whereas patients with early relapse and nonresponse experienced a significantly shorter time to CRPC and OS (P < 0.001). Eighty-one patients developed CRPC; first-line docetaxel (n = 35) and ARPI (n = 26) achieved comparable OS (P = .849).

CONCLUSION

The efficacies of abiraterone, enzalutamide, and apalutamide were equivalent if the baseline imbalances were mitigated. Sustained PSA suppression <0.2 ng/mL for 12 months predicts favorable outcomes, regardless of the speed of decline, whereas failure to achieve or maintain this threshold is associated with poorer prognosis. The choice between docetaxel and alternative ARPI for first-line treatment of metastatic CRPC showed no survival differences.