The impact of the 2025 NCCN update in defining very high-risk prostate cancer on surgical outcomes after robot-assisted radical prostatectomy: A retrospective cohort analysis.

Abstract

340 Background: Under the pre-2025 National Comprehensive Cancer Network (NCCN) definition, very high-risk (VHR) prostate cancer (PCa) included any of the following: clinical stage cT3b–T4, primary Gleason pattern 5, more than four biopsy cores with Grade Group (GG) 4–5, or multiple NCCN high-risk features. In 2025, the NCCN revised the VHR definition to include patients meeting at least two of the following: clinical stage ≥cT3, prostate-specific antigen (PSA) ≥40 ng/mL, and GG ≥4. This change, largely derived from radiotherapy trials evaluating the addition of abiraterone to androgen deprivation therapy with radiotherapy, substantially alters the composition of the VHR group. Importantly, this revised definition has not been validated in surgically treated cohorts, raising questions about its applicability to patients undergoing robot-assisted radical prostatectomy (RARP). We aimed to compare oncological and pathological outcomes under the pre-2025 and 2025 NCCN definitions among individuals treated with RARP without perioperative systemic therapy. Methods: We retrospectively reviewed 1,879 patients who underwent RARP at two institutions between July 2012 and November 2022. Of these, 641 patients classified as high risk or above were analyzed: historical high risk (Group 1: n = 379), reclassified from VHR to high risk under the 2025 definition (Group 2: n = 117), and VHR per 2025 criteria (Group 3: n = 145). Results: The median follow-up was 59.8 months. In terms of postoperative pathology, Group 2 exhibited significantly more adverse features, including higher pathological stage, Gleason grade, positive surgical margins, and lymph node involvement compared with Group 1, whereas no significant differences were observed between Groups 2 and 3. Five-year biochemical recurrence–free survival rates were 71.1%, 44.7%, and 29.8%; metastasis-free survival rates were 99.6%, 94.1%, and 88.9% for Groups 1, 2, and 3, respectively. Group 2 showed significantly worse outcomes than Group 1.Exploratory analyses within Group 3 revealed that patients with more than four biopsy cores containing GG 4–5 had markedly worse recurrence outcomes, whereas those without this factor demonstrated results closer to Group 2. Conclusions: The 2025 NCCN redefinition of high-risk prostate cancer, primarily based on radiation therapy data, substantially restructured patient classification while highlighting diversity within the surgical treatment group. Further validation in RARP cohorts is needed, and more precise risk stratification could guide individualized perioperative and multidisciplinary treatment strategies.