Abstract
OBJECTIVE: This study aimed to compare the outcomes of neoadjuvant novel hormonal therapy (NHT) versus classical hormonal therapy (CHT) before radical prostatectomy (RP) in patients with locally advanced prostate cancer. METHODS: Propensity score matching (2:1) was performed to minimize the effect of confounders at our center. We retrospectively analyzed 99 patients who received neoadjuvant hormonal therapy for 3-6 months from March 2019 to April 2023. The novel hormonal agents included apalutamide, darolutamide, or enzalutamide, whereas the classical hormonal agent was bicalutamide. The primary endpoint was pathological response. Secondary outcomes included prostate specific antigen (PSA) complete response rate, biochemical recurrence-free survival (bRFS), and biochemical response rate. RESULTS: After propensity score matching, 63 patients were matched to the CHT group and 36 patients were matched to the NHT group. All patients received androgen deprivation therapy. Pathological response Group 0 was not observed in either group; 41.3% (26/63) of patients in the CHT group achieved a complete response (Group 1), compared with 52.8% (19/36) in the NHT group. Neoadjuvant NHT showed significant advantages over CHT in reducing prostate volume (p < 0.001), downstaging (p = 0.012), and the PSA complete response rate (p = 0.002). PSA complete response was an independent predictor for complete response (OR 2.8, 95%CI 1.14-6.88, p = 0.025). Neoadjuvant NHT also demonstrated a significant improvement in bRFS compared with CHT, and there was a 70% lower risk of biochemical recurrence in the NHT group (HR 0.3, 95% CI 0.17-0.55, p = 0.0006). CONCLUSION: Neoadjuvant NHT resulted in superior pathological responses and PSA responses compared with neoadjuvant CHT in patients with locally advanced prostate cancer. Lower PSA values prior to RP were associated with complete response. Our findings highlighted a significant benefit of neoadjuvant NHT in improving bRFS. CLINICAL TRIAL NUMBER: Not applicable.