Background: To define whether in locally advanced prostate cancer submitted to radical retropubic prostatectomy (RRP) the presence of a Gleason score 8–10 represents an index of high risk for progression and cancer-specific death. Methods: Finally, a total of 130 men with pathologically confirmed T3 cancer were included in this analysis. On the basis of the histological grade obtained at RRP, patients were divided into two groups: patients with a Gleason score 8–10 (group 1) and patients with a Gleason score <8 (group 2). Postoperative follow-up ranged from 24 to 120 months (median 60). After RRP no patients received additional treatments until a biochemical or clinical disease progression was found. Kaplan-Meier projections were used in each group. Results: After RRP, 41 patients (31.5%) had a Gleason score 8–10 tumor. The incidence of positive lymph nodes was significantly higher (p = 0.0030) in group 1 (36.6%) when compared with group 2 (12.3%). Significant differences between the two groups were also found with respect to seminal vesicle involvement (p = 0.0045) and positive surgical margins (p = 0.0040). The actuarial cumulative disease-specific survival for group 1 and group 2 was, respectively, 69 and 82% at 10 years. A Kaplan-Meier analysis demonstrated a 100% disease-specific survival, a 92% clinical progression-free survival and a 38% biochemical progression-free survival 10 years postoperatively if patients in group 1 had negative surgical margins and negative lymph nodes (48.8%). Conclusions: Our data indicate a significant association between Gleason score 8–10 and disease-specific survival, only if patients in group 1 are stratified on the basis of surgical margins and/or lymph node involvement.

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