Impact of Gleason Grade at the Positive Surgical Margin on Biochemical Recurrence After Radical Prostatectomy in pT2N0 Prostate Cancer.

INTRODUCTION: Positive surgical margin (PSM) predicts biochemical recurrence (BCR) after radical prostatectomy (RP), but the prognostic role of Gleason grade (GG) at the PSM remains unclear. We assessed whether PSM GG independently predicts BCR in organ-confined prostate cancer (PCa). PATIENTS AND METHODS: This retrospective cohort study included 4,659 patients with pT2N0 PCa treated with RP at three tertiary centers, stratified by PSM status (negative, GG3, GG4). The primary outcome was BCR-free survival. Multivariable Cox regression adjusted for age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, and lymphovascular invasion (LVI). Model performance was assessed using concordance index (C-index), Akaike information criterion (AIC), and time-dependent ROC curves. Sensitivity analyses included subgroup, landmark, and propensity score-matched approaches. RESULTS: PSM were present in 9.4% (74.8% GG3, 25.2% GG4). At median follow-up 45 mo, higher PSM grade predicted worse BCR-free survival (p<0.001). Among PSM cases, GG4 had higher BCR risk than GG3 (HR 2.23, p=0.002). Versus negative margins, GG3 and GG4 increased BCR risk 3.26-fold and 4.16-fold (both p<0.001). PSM grade improved model discrimination (C-index 0.739 vs. 0.672) and reduced AIC. Stronger effects in lower ISUP grade and age 60-70. GG4 independently predicted early recurrence (OR 3.34, p=0.006). CONCLUSION: GG at the PSM independently predicts BCR, with the strongest effect in lower-grade tumors (ISUP 1-2; HR 7.08 for GG4), attenuated in high-grade disease (HR 2.98). Higher PSM grades increase recurrence risk, especially in otherwise favorable tumors, supporting context-specific use in postoperative risk stratification.