Researchers aimed to evaluate the efficacy of radical prostatectomy (RP) as initial treatment for high-risk prostate cancer (HRPC) against neoadjuvant therapy with a novel hormonal agent (NHA) prior to radical prostatectomy (neo-RP) in this setting. 

The neo-RP group was composed of HRPC 112 patients who had received treatment in 1 of 3 studies of neoadjuvant NHA followed by RP. In addition, patients with HRPC who met key inclusion criteria for the neoadjuvant trials (i.e.,≥3 positive biopsy cores and Gleason ≥4+3=7) who underwent RP without neoadjuvant therapy between 2010 and 2016 at an institution were included in the RP group (259). The estimation of treatment effects was conducted using inverse probability of treatment weighting (IPTW), which takes into account fewer confounding variables.

Time to biochemical recurrence (BCR) and progression-free survival were the primary endpoints (MFS). After IPTW, there was parity between the 2 groups with respect to pre-IPTW differences in Gleason 9-10 cancer grade (46% vs. 24%), cT3 disease stage (22% vs. 5%), and PSA more than or equal to 20 ng/ml (14% vs. 7%). The median time to BCR and median time to progression following IPTW were also substantially longer in the neo-RP group than in the RP group (HR=0.25 [95% CI 0.18-0.37] and HR=0.26 [0.15-0.46], respectively). 

The neo-RP group had reduced rates of both adjuvant (7% vs. 24%) and salvage therapy (3.4% vs 46%). The time to BCR and overall survival (OS) were both improved in males with HRPC who underwent neoadjuvant therapy with an NHA before undergoing RP, as opposed to those who underwent RP immediately after diagnosis. These results are speculative, but they do support further investigation into the potential benefits of an NHA in neoadjuvant therapy for HRPC, an approach being investigated in the ongoing phase 3 PROTEUS trial (NCT03767244).