Impact of the 2025 NCCN Definition Change for Very High-Risk Prostate Cancer on Surgical Outcomes After...

In 2025, the National Comprehensive Cancer Network (NCCN) updated the definition of very high-risk (VHR) prostate cancer to include individuals meeting at least two of the following: clinical stage ≥ T3, prostate-specific antigen ≥ 40 ng/mL, and Gleason Grade Group (GG) ≥ 4. This revision alters group classification and may impact surgical outcomes. We aimed to compare oncological outcomes under the earlier and 2025 definitions in individuals undergoing robot-assisted radical prostatectomy (RARP) without perioperative systemic therapy.

We retrospectively reviewed 1879 individuals who underwent RARP at two institutions between July 2012 and November 2022. Of these, 641 classified as high risk or above were analyzed: historical high risk (Group 1: n = 377), reclassified from VHR to high risk (Group 2: n = 119), and VHR per 2025 criteria (Group 3: n = 145).

The median follow-up was 59.8 months. 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 the three groups, respectively. Group 2 showed worse outcomes than Group 1. Exploratory analyses indicated that within Group 3, having > 4 biopsy cores with GG 4-5 was associated with significantly worse recurrence outcomes, whereas those without this factor had results closer to Group 2.

In conclusion, both the revised high-risk and VHR categories include heterogeneous populations. Refinement of risk stratification in the surgical setting may help identify subsets requiring tailored perioperative and multimodal strategies.