Oncologic Outcomes in a Contemporary “PROTEUS-like” Cohort of High-risk Prostate Cancer Treated with Radical Prostatectomy Without Neoadjuvant Hormonal Therapy

Background and objective High-risk prostate cancer (PCa) carries substantial risks of recurrence, metastasis, and mortality. Neoadjuvant therapy before radical prostatectomy (RP) remains investigational. The PROTEUS (NCT03767244) trial evaluates perioperative apalutamide + androgen deprivation therapy (ADT) but lacks a surgery-only control cohort. The objective of this study is to characterize oncologic outcomes in patients with PROTEUS-like high-risk PCa undergoing RP without neoadjuvant therapy. Methods We performed a retrospective, single-center cohort study of consecutive patients fulfilling PROTEUS high-risk criteria who underwent RP with lymphadenectomy without prior ADT or neoadjuvant treatment. The primary outcome was biochemical recurrence–free survival (BCR-FS). Secondary outcomes included metastasis-free survival (MFS), event-free survival (EFS), and cancer-specific survival (CSS). Key findings and limitations Among 1392 patients, median follow-up was 60 mo (95% confidence interval [CI], 56–64); 67% received postoperative radiotherapy. BCR-FS at 36, 60, and 120 mo was 60% (95% CI, 57–64), 44% (95% CI, 40–49), and 22% (95% CI, 17–28), respectively. MFS was 79% (95% CI, 76–83), 71% (95% CI, 66–76), and 56% (95% CI, 47–65), respectively. EFS was 56% (95% CI, 52–60), 40% (95% CI, 36–45), and 18% (95% CI, 13–23), respectively. CSS remained high at 95.5% (95% CI, 94–97), 92% (95% CI, 90–94), and 86% (95% CI, 81–91), respectively. Limitations include the retrospective, single-center design, absence of centralized pathology review, and maturing follow-up. Conclusions and clinical implications These findings demonstrate substantial rates of recurrence and metastatic progression despite contemporary management, underscoring the persistent unmet need in this population and providing a rationale for prospective evaluation of perioperative treatment intensification strategies such as PROTEUS.