Validation of the Combination Gleason Score as an Independent Favorable Prognostic Factor in Prostate Cancer Treated With Dose-Escalated Radiotherapy

Abstract

Prognostic factors that alter prostate cancer effect include TNM stage, pre-treatment PSA, Gleason score, and Gleason grade group (2). Of these, Gleason score yields the largest impact on cause-specific survival (CSS) (5). While Gleason score is crucial to predicting outcomes, disparity between biopsy and prostatectomy sample scores is often seen. This can result in Gleason score upgrading (GSU) and downgrading (GSD) at the time of surgery. Phillips et al. explored this phenomenon through combining the lowest and highest Gleason scores at biopsy (ComboGS) and examining how such a factor would impact GSU and prostate cancer specific survival (PCSM). This study aims to validate the Phillips et al. findings via an independent cohort of prostate cancer patients treated with definitive dose-escalated radiation therapy (DE-RT) at a single institution.DE-RT was administered to 2,539 men; 687 men had a ComboGS. We utilized univariate and multivariable analysis to evaluate relapse rates and clinical outcomes. To further ascertain the ComboGS prognostic impact, we employed the Cancer of the Prostate Risk Assessment Score (CAPRA) and the modified CAPRA (mCAPRA). Rates of biochemical event-free survival (bEFS) and distant metastasis-free survival (DMFS) were compared across CAPRA scores, with and without modification, and the prognostic value of the CAPRA scores were compared using Harrel's concordance index (C-index) (12).ComboGS presence in Gleason 7-10 prostate cancer patients generated improved 10-year biochemical event-free survival (bEFS) from 76.6% to 82.4% (HR 0.75, CI 0.59-0.96, P = 0.021), 10-year distant metastasis-free survival (DMFS) from 89.3% to 93.2% (HR 0.57, CI 0.39-0.85, P = 0.005), 10-year PCSM from 93.9% to 97.4% (HR 0.39, CI 0.21-0.7, P = 0.001) and 10-year overall survival (OS) from 65.7% to 75.6% (HR 0.69, CI 0.57-0.83, P < 0.001). Multivariable analysis also supported that ComboGS is protective for biochemical failure (HR 0.64, CI 0.50-0.83, P < 0.001), distant metastasis (HR 0.42, CI 0.28-0.63, P < 0.001), death from prostate cancer (HR 0.32, CI 0.17-0.58, P < 0.001), and overall mortality (HR 0.65, CI 0.54-0.79, P < 0.001). Additionally, adjusting the CAPRA score for ComboGS decreased the risk of biochemical failure (BF) by nearly 30% (HR = 0.70 [95% CI, 0.55-0.88], P = 0.003) and by 50% (HR = 0.54 [95% CI, 0.37-0.80], P = 0.002) for distant metastasis.ComboGS is a useful and readily available independent prognostic factor for all clinical endpoints (biochemical failure, distant metastasis, cancer-specific survival and overall survival). Moreover, the ComboGS can be used in conjunction with the extensively validated CAPRA scoring, to better risk stratify patients being treated with definitive DE-RT and possibly de-escalate therapy for some men with ComboGS 7 disease.