Comparison of oncologic outcomes following robot-assisted radical prostatectomy in high- and very high-risk prostate cancer based on the 2025 National Comprehensive Cancer Network risk stratification.

INTRODUCTION

National Comprehensive Cancer Network (NCCN) risk stratification was updated in 2025. We compared oncologic outcomes between high-risk (HR) and very high-risk (VHR) prostate cancer following robot-assisted radical prostatectomy (RARP).

METHODS

Among 14,878 men who underwent RARP from 2008 to 2023, 2,871 and 100 met the 2025 NCCN HR and VHR criteria. Cumulative incidences of biochemical recurrence (BCR), cancer-specific mortality, and all-cause mortality were compared between two groups using Kaplan-Meier curves and log-rank tests. Prostate-specific antigen (PSA) persistence was also compared. Multivariable logistic and Cox regression models were used to adjust for potential confounders: age, race, ethnicity, comorbidity, neoadjuvant hormonal therapy, and surgery year. Further, we conducted multivariable analyses to identify VHR features (cT3-4, grade group 4-5, and PSA > 40 ng/ml) associated with PSA persistence and BCR.

RESULTS

VHR patients were 4.25 and 3.37 times more likely to have pT4 and pN1 disease, respectively; 35% exhibited PSA persistence. After adjustment, VHR patients continued to exhibit higher risks of PSA persistence (odds ratio: 3.67, 95% CI: 2.38-5.58) and BCR (hazard ratio: 2.36, 95% CI: 1.65-3.38). Cancer-specific and all-cause mortality were comparable; however, the short follow-up (median 48 months, interquartile range: 24-72) limited mortality analyses. All VHR features were independent predictors of PSA persistence and BCR.

CONCLUSIONS

The 2025 NCCN VHR stratification is associated with adverse pathology, PSA persistence, and BCR. Preoperative counseling-including discussion of the potential need for neoadjuvant, adjuvant, and salvage therapy-and meticulous patient selection are essential when considering RARP as an initial treatment for patients with HR, particularly VHR disease, within a multidisciplinary framework.