Pathological Stage and Grade Determine the Impact of Focal Versus Extensive Positive Surgical Margins After Radical Prostatectomy

Purpose: the prognostic value of positive surgical margins (PSMs) after radical prostatectomy (RP) remains debated, particularly when distinguishing focal from extensive involvement. Moreover, the interaction between margin status and other adverse pathological features, such as tumour stage, grade, and nodal status, is not fully defined. The study aims to evaluate the impact of focal and extensive PSMs on biochemical recurrence-free survival (BCRFS), stratified by pathological stage, Gleason grade, and nodal involvement. Methods: we retrospectively analyzed 1258 patients who underwent robot-assisted RP between 2017 and 2023, evaluating BCRFS as primary endpoint. Survival was analyzed using Kaplan–Meier and log-rank tests across margin categories (negative, focal, extensive). Analyses were stratified by pT stage (pT2–pT3b), ISUP grade (<3 vs. ≥3), and nodal status (pN0/pNx vs. pN+). Median follow-up was 39 months (IQR 24–62), and 5-year BCRFS was used as the reference endpoint. Results: median age was 68 years and median PSA 6.9 ng/mL. Stage distribution: pT2 56.4%, pT3a 29.8%, pT3b 13.6%; 16.6% were pN+. ISUP grade ≥ 3 was observed in 60.6%. Overall, 20.3% developed biochemical recurrence. In pT2 tumours or primary Gleason pattern 3, focal PSMs showed 5-year BCRFS of 88–90%, very similar to negative margins (91–93%) and clearly better than extensive PSMs (~72%). In pT3 tumours or primary Gleason pattern 4, focal PSMs showed 5-year BCRFS of ~55–60%, similar to extensive PSMs (~40–50%) and significantly worse than negative margins (78% in pT3a and 65% in pT3b, p < 0.01). In N + 5-year BCRFS was similarly poor in negative (~45%), focal (~42%), and extensive margins (~40%, p = 0.455). Conclusions: the prognostic impact of positive surgical margins depends on tumour biology. In organ-confined or ISUP ≤ 2 disease, focal PSMs show recurrence rates similar to negative margins and may be managed with observation. In locally advanced or ISUP ≥ 3 tumours, both focal and extensive PSMs carry a markedly higher risk of biochemical recurrence and might suggest an early intervention. PSMs lose discriminatory value in node-positive patients.