Validation of the Combination Gleason Score as an Independent Favorable Prognostic Factor in GS 7-10 Prostate Cancer Treated With Dose-Escalated Radiation Therapy

Abstract

The combination Gleason Score (ComboGS) at time of biopsy is a recently proposed prognostic marker defined as the presence of at least 1 biopsy core of lower Gleason Score (GS) in men who have a highest GS ≥7 prostate cancer. In single-institution reports, the presence of ComboGS decreased the risk of pathologic upgrading at time of prostatectomy and decreased the risk of prostate cancer-specific mortality (PCSM) following external beam radiation therapy (EBRT); however, these findings have not been validated. Herein, we evaluated if the presence of ComboGS was prognostic for improved outcome in an independent cohort of men receiving EBRT for prostate cancer. At a single institution from 1988 to 2012, 788 consecutive men with prostate cancer received dose-escalated EBRT (minimum 75 Gy). Endpoints analyzed included PCSM, overall survival (OS), freedom from distant metastases (FFDM) and freedom from biochemical failure (FFBF, with failure defined as a rise in prostate-specific antigen [PSA] of 2 ng/mL or more above nadir). Statistical analysis was performed using Kaplan-Meier and Stepwise Cox proportional hazards models. In the 532 men with a GS of 7-10, the median follow-up was 89 (interquartile range [IQR]:57-128) months. Of these men, 259 (49%) had a ComboGS, while 272 (51%) did not. Men with ComboGS had similar age, T stage, Cancer of the Prostate Risk Assessment (CAPRA) score, and rate of androgen deprivation therapy (ADT) use (P>.05). Men with comboGS had higher baseline GS (7, 57% vs 67%; 8, 15% vs 17%; 9, 20% vs 9.5%; 10, 8% vs 7%, P=.005), and slightly lower PSA (14.2 vs 16.3, P=.02). On univariate analysis, men with ComboGS had improved 10-year FFBF (75.2% vs 54.9%, HR: 0.59, 95% CI: 0.42-0.82), FFDM (95.7% vs 84.3%, HR: 0.26, 95% CI: 0.15-0.47), PCSM (93.7% vs 88.1%, HR: 0.42, 95% CI: 0.22-0.81), and OS (82.4% vs 67.7%, HR: 0.45, 95% CI: 0.31-0.64). In men with intermediate-risk disease, the presence of comboGS decreased 10-year distant metastasis (DM) rates from 7.2% (±2.3) to 0.8% (±0.8) (HR: 0.17, 95% CI: 0.53-0.57), while in high-risk men, 10-year DM rates decreased from 21.9% (±4.1) to 9.1% (±3.5) (HR: 0.32, 95% CI: 0.17-0.63). On multivariate analysis, ComboGS was associated with decreased BF (HR: 0.59, 95% CI: 0.40-0.86, P=.007), DM (HR: 0.20, 95% CI: 0.09-0.43, P=.0001), PCSM (HR: 0.37, 95% CI: 0.16-0.85, P=.02), and OS (HR: 0.32, 95% CI: 0.20-0.52, P<.0001) after correction for age, GS, PSA, T stage, Charlson Co-Morbidity Index, percent cores positive, and ADT use. The addition of ComboGS increased the prognostic power of CAPRA score as measured by the concordance index for BF (0.709 vs 0.693), DM (0.833 vs 0.801), and PCSM (0.827 vs 0.811). ComboGS is an independent favorable prognostic factor for all clinical endpoints that is readily available but not routinely utilized. ComboGS increases the prognostic power of the CAPRA score and may identify men in whom therapy may be de-escalated