Preoperative characteristics of high‐Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

OBJECTIVE To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8 – 10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP). PATIENTS AND METHODS The Institutional Review Board-approved institutional RP database (1982 – 2010) was analysed for men with high-Gleason prostate cancer on biopsy; 842 men were identified. The 10-year biochemical-free (BFS), metastasis-free (MFS) and prostate cancer-specific survival (CSS) were calculated using the Kaplan – Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8 – 10 and pT3b or N1. Preoperative characteristics were compared using appropriate comparative tests. Logistic regression determined preoperative predictors of unfavourable pathology. RESULTS There was favourable pathology in 656 (77.9%) men. The 10-year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively. In contrast, men with unfavourable pathological findings had significantly worse 10-year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001). In multivariable logistic regression, a prostate-specific antigen (PSA) concentration of > 10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38 – 3.62, P = 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55 – 4.21, P 50% positive core involvement (OR 2.25, 95% CI 1.17 – 4.35, P = 0.015) were predictive of unfavourable pathology. CONCLUSIONS Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis. Among men with high-Gleason sum at biopsy, a PSA concentration of > 10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high-grade cancer and > 50% core involvement are predictive of unfavourable pathology. Keywords: prostate cancer, high-risk, Gleason sum, outcomes INTRODUCTION For men undergoing radical prostatectomy (RP) for prostate cancer, biopsy and pathological Gleason sum are cited as the strongest predictors of outcome in pre- and postoperative models, respectively [1-5]. Although 80% of men with Gleason 8 – 10 prostate cancer undergoing RP at our institution have biochemical recurrence by 15 years, not all patients do uniformly poorly with respect to metastases-free (MFS) and prostate cancer-specific survival (CSS). A recent multivariate evaluation of long-term surgical outcomes in men with pathological Gleason sum 8 – 10 prostate cancer determined that pathological stage at RP was the most potent indicator of mortality [6]. Men with organ-confined (pT2) or extraprostatic (pT3a,) disease at RP had a 76 – 96% CSS at 15 year compared with 37 – 73% at 15 years for men with seminal vesicle invasion (pT3b, SVI) or lymph node involvement (N1) [6]. These divergent outcomes make the ideal management of high-Gleason sum prostate cancer controversial. While recent studies suggest that inclusion of surgery in the treatment of men with Gleason sum 8 – 10 on biopsy allows for better long-term outcomes when compared with radiation [7,8], many urologists are hesitant to subject these men to the side-effects of RP when benefit may be marginal. Little data exists about the best preoperative criteria to identify men with high-Gleason sum prostate cancer who may benefit from surgery. One recent study suggests that men with a single high-risk feature (PSA concentration of > 20 ng/mL, Gleason 8 – 10 or clinical stage > cT2b [3]) have better outcomes than men with multiple high-risk features, but this work did not thoroughly explore the utility of individual preoperative parameters to predict advanced pathological stage [9]. In the present study, we evaluated the ability of preoperative characteristics, to predict favourable pathological and oncological outcomes in men found to have high Gleason sum at biopsy.