Comparing outcomes between neoadjuvant hormonal therapy followed by prostatectomy versus upfront prostatectomy in high-risk prostate cancer: The road ahead

Neoadjuvant treatment before definite surgical resection is the standard of care for many malignancies, but prostate cancer is not one of them. Ravi et al. performed a comparative analysis of oncological outcomes in high-risk prostate cancer(HRPC) patients who either received 6 months of neoadjuvant androgen deprivation therapy (ADT) with a novel hormonal agent before radical prostatectomy (RP), designated as the neo-RP cohort or those who underwent an upfront RP, designated as the RP cohort.[1] HRPC was defined as Gleason grade =8, prostate-specific antigen (PSA) >20 ng/ml, and/or =cT3 disease. Patients included in the neo-RP group were treated with either enzalutamide or abiraterone in a trial setting between 2010 and 2016.[2-4] The RP cohort included patients undergoing upfront RP between 2010 and 2016 with similar baseline disease characteristics as the neo-RP cohort. The decision to initiate adjuvant or salvage therapy was at the discretion of the treating physician in both cohorts. The primary outcomes were the development of biochemical recurrence (BCR) and metastasis-free survival (MFS). A total of 112 and 247 patients in the neo-RP and RP cohorts were analyzed after propensity score matching and inverse probability of treatment weighting (IPTW). 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 two cohorts were balanced. In the neo-RP and RP cohorts, the mean age was 61 years in both, mean PSA (ng/ ml) at diagnosis was 15 and 12, 50% and 46% had Gleason scores of 9–10, and 77% and 78% had T1 or T2 tumors, respectively. Pathological outcomes were favorable in the neo-RP group as compared to the RP group with 11 (10%) and 13 men (12%) achieving a pathological complete response and minimal residual disease (i.e. =5 mm residual tumor), respectively, and a lower incidence of positive margins (13% vs. 56%) and pT3-T4 disease (55% vs. 72%, both P < 0.01). The pathological nodal burden was similar between groups. At a median follow-up after RP of 3.7 years and 4 years for the neo-RP and RP groups, time to BCR was significantly longer in the neo-RP group (weighted hazard ratio =0.25 [95% confidence interval 0.18–0.37], P < 0.01), with 3-year freedom from BCR of 59% and 15%, respectively, along with longer MFS (weighted HR = 0.26 [0.15–0.46], P < 0.01), with 3-year MFS of 96% and 68%, respectively. Eight (7%) and 63 (24%) men received adjuvant radiotherapy (± ADT) and 38 (34%) and 118 (46%) men received salvage radiotherapy (± ADT) with a median time to therapy of 7.6 and 4.1 months, in the neo-RP and RP groups, respectively, with both rates lower in the neo-RP group. © 2023 Wolters Kluwer Medknow Publications. All rights reserved.