Comparing NCCN-based risk groups to the PROTEUS definition of high-risk localized prostate cancer to inform peri-operative care

Background There is substantial heterogeneity of outcomes among patients with high-risk localized prostate cancer. The recently published PROTEUS trial saught to enrich for aggressive disease using more restrictive eligibility criteria than the commonly used NCCN high-risk definition. We compared patient distributions and oncologic outcomes after radical prostatectomy using PROTEUS and NCCN high-risk criteria.Methods We used an institutional radical prostatectomy database to classify patients as high-risk by NCCN criteria (Gleason grade group [GGG] 4-5, clinical T3-T4 disease, or PSA > 20 ng/ml) or PROTEUS criteria (overall GGG ≥ 3 plus GGG5 in ≥1 core, GGG4 in ≥2 cores each with >80% involvement, GGG3+ in ≥6 systematic cores, or GGG3+ in ≥3 systematic cores with PSA ≥ 20 ng/ml). Patient distributions were summarized descriptively. Area under the receiver operating curve (AUC) was compared for oncologic outcomes.Results Among 358 patients, 62 (17%) met NCCN high-risk criteria and 44 (12%) met PROTEUS criteria. Overall, 38 patients met both definitions, 24 met NCCN criteria only, and 6 met PROTEUS criteria only. There were no statistically significant differences in predicting extra-prostatic extension (NCCN 0.56, 95% Confidence interval [CI] 0.52-0.60; PROTEUS 0.56, 95% CI 0.53-0.60; P = 0.96), positive surgical margins (NCCN 0.54, 95% CI 0.49-0.58; PROTEUS 0.52, 95% CI 0.49-0.56; P = 0.45), and PSA > 0.2 at 12 months postoperatively (NCCN 0.59, 95% CI 0.49-0.69; PROTEUS 0.64, 95% CI 0.54-0.75; P = 0.32).Conclusion PROTEUS criteria, which may be cumbersome in clinical practice, identified a smaller, overlapping, but nonidentical high-risk population compared with NCCN criteria. There were no statistically significant differences in postprostatectomy oncologic outcomes between both definitions. These findings suggest that PROTEUS eligibility criteria represent a more restrictive trial-enrichment definition but may not meaningfully improve discrimination of adverse outcomes relative to standard NCCN high-risk classification.