Impact of Neoadjuvant Chemohormonal Therapy With GnRH Antagonist and Low-Dose Estramustine in Very High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy.

Abstract

Background: High-risk patients with prostate cancer (PC) frequently experience biochemical recurrence (BCR) after surgery. Thus numerous studies have investigated the efficacy of neoadjuvant therapies for high-risk PC patients; however, no protocol has been established. This study aimed to assess the effect of androgen deprivation therapy combined with low-dose estramustine phosphate (EMP) on BCR compared with androgen deprivation therapy (ADT) alone in high- and very high-risk patients with PC.

Methods: This retrospective study targeted patients with PC meeting the National Comprehensive Cancer Network high-risk criteria (cT1-4N0M0), with 173 patients in the exposure group who received neoadjuvant chemohormonal therapy (gonadotropin-releasing hormone [GnRH] antagonist combined with low-dose EMP), and 490 patients in the control group treated with and neoadjuvant hormone therapy (NHT) (ADT ± first-generation anti-androgens). Data for each group were extracted from a database of patients who underwent robot-assisted laparoscopic prostatectomy at 25 tertiary care centers across Japan between 2011 and 2023. The inverse probability of treatment weighting was used to adjust for baseline differences. The primary outcome was BCR-free survival, with hazard ratios (HRs) calculated using a Cox proportional hazards model between the high-risk and very high-risk groups.

Results: After adjustment, the standardized mean difference was < 0.1. The exposure group had 3 and 5-year BCR-free survival rates of 82.1% and 74.6%, respectively, compared with 70.8% and 64.4% in the control group (HR: 0.55; 95% confidence interval [CI]: 0.35-0.88). For high-risk patients, the rates were 87.1% and 84.2% at both 3 and 5 years in the intervention group and 83.5% and 75.0% in the control group (HR: 0.66; 95% CI: 0.30-1.47). For very high-risk patients, the 3-year and 5-year rates were 75.3% and 65.7% in the intervention group and 57.3% and 53.6% in the control group (HR: 0.53; 95% CI: 0.30-0.92).

Conclusions: In patients with very high-risk PC undergoing robot-assisted laparoscopic prostatectomy, a GnRH antagonist and low-dose EMP yielded better BCR-free survival outcomes than NHT.