BACKGROUND: This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3 months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics. RESULTS: ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3 months (1.47 vs 0.52 ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345 ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5 days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5 ng/ml and time to nadir ≥ 145 days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45 ng/ml and time to nadir ≥ 70 days were optimal with ARSI. CONCLUSION: No significant differences in PSA response was seen between groups
however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.