Oncologic Outcomes in a Contemporary "PROTEUS-like" Cohort of High-risk Prostate Cancer Treated with Radical...

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.

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).

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.

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.