Neoadjuvant Novel Hormonal Therapy Followed by Prostatectomy versus Up-Front Prostatectomy for High-Risk Prostate Cancer: A Comparative Analysis

We sought to compare outcomes between neoadjuvant therapy with a novel hormonal agent (NHA) prior to radical prostatectomy (neo-RP) and up-front radical prostatectomy (RP) in patients with high-risk prostate cancer (HRPC).HRPC patients treated on 3 trials of neoadjuvant NHA followed by RP formed the neo-RP cohort (112). The RP group (259) comprised an observational cohort of HRPC patients undergoing RP without neoadjuvant therapy between 2010-2016 at our institution who met key eligibility criteria for the neoadjuvant trials (ie ≥3 positive biopsy cores and Gleason ≥4+3=7). Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors when estimating treatment effects. The primary outcomes were time to biochemical recurrence (BCR) and metastasis-free survival (MFS).Before IPTW, the neo-RP cohort had higher rates of Gleason 9-10 cancer (46% vs 24%), cT3 disease (22% vs 5%), and PSA ≥20 ng/ml (14% vs 7%); after IPTW, the 2 cohorts were balanced. Overall, after IPTW, time to BCR (HR=0.25 [95% CI 0.18-0.37]) and MFS (HR=0.26 [0.15-0.46]) were significantly longer in the neo-RP compared to the RP cohort. Rates of adjuvant (7% vs 24%) and salvage therapy (34% vs 46%) were lower in the neo-RP cohort.Neoadjuvant therapy with an NHA prior to RP was associated with longer time to BCR and superior MFS compared to up-front RP in men with HRPC. These findings are hypothesis-generating but suggest benefit with neoadjuvant therapy with an NHA in HRPC, an approach which is currently being studied in the phase 3 PROTEUS trial (NCT03767244).