Long-Term Follow-Up of Neoadjuvant Enzalutamide Plus Androgen Deprivation Therapy in Localized Prostate Cancer: A...

Neoadjuvant intense androgen deprivation therapy (ADT) with androgen receptor signaling inhibitors (ARSIs) has shown pathologic complete responses (pCR) in prostate cancer (PCa), but long-term survival outcomes remain unclear. This study evaluates the durability of response following neoadjuvant ADT plus enzalutamide before robot-assisted radical prostatectomy (RARP) and lymph node dissection.

We conducted a secondary analysis of an open-label feasibility trial enrolling men with NCCN intermediate-, high-, very high-risk localized and regional PCa treated with 6 months of neoadjuvant ADT and enzalutamide. Factors associated with biochemical recurrence (BCR) and metastases were evaluated using appropriate univariable statistical tests, and BCR-, metastasis-free survival (MFS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method.

Of 39 patients enrolled, 36 patients completed all study interventions. Eighteen (66.7%) patients had NCCN very high-risk disease or clinical regional lymph nodes on imaging. Four patients (11.1%) achieved pCR, although two (5.6%) developed BCR. One patient (2.8%) had M1 and three (8.3%) had N1 disease on final pathology, and all four developed metastases. Eleven (30.6%) patients received salvage therapy, with all but one receiving ADT with radiation. Factors associated with BCR included biopsy ISUP grade and positive surgical margins, while NCCN risk group, biopsy ISUP grade, perineural invasion, and pathological stage were associated with metastases (p < 0.05). Median follow-up was 7.3 (95% CI 6.3-8.3) years, and the 5-year BCR-free survival, MFS, and CSS were 64.1%, 84.6%, and 94.3%, respectively.

Neoadjuvant enzalutamide and ADT was associated with favorable long-term oncologic outcomes, supporting continued investigation in localized PCa.