Weighted Gleason Grade Group (WGGG): A new prostate cancer biopsy reporting system with prognostic potential

Introduction: Presently, prostate biopsy (PBx) results report the highest Gleason Grade Group (GGG) as a single metric that gauges the overall clinical aggressiveness of cancer and dictates treatment. We hypothesized a PBx showing multiple cores of cancer with more volume cancer per core would represent more aggressive disease. We propose the Weighted Gleason Grade Group (WGGG), a novel scoring system that synthesizes all histopathologic data and cancer volume into a single numeric value representing the entire PBx, allowing for improved prediction of adverse pathology and risk of biochemical recurrence (BCR) following radical prostatectomy (RP). Methods: We studied 171 men who underwent RP after standard PBx. The WGGG was calculated by summing each positive core using the formula: GGG + (GGG x %Ca/core). RP pathology was evaluated for extraprostatic extension (EPE), positive surgical margins (PSM), seminal vesicle invasion (SVI), and lymph node involvement (LNI), and patients were followed for BCR. We compared GGG vs. WGGG receiver operating characteristic curves for each outcome, and determined the predictive capability of GGG and WGGG to identify patients with BCR. Categorized WGGG groups were created based on risk of BCR using classification and regression tree analysis. We then sought to externally validate WGGG in a cohort of 389 patients in a separate institutional dataset. Results: In the development cohort, area under the curves (AUCs) for the WGGG vs. GGG were significantly higher for predicting EPE (0.784 vs. 0.690, P = 0.002), SVI (AUC 0.823 vs. 0.721, P =.014), LNI (AUC 0.862 vs. 0.823, P = 0.039), and PSM (AUC 0.638 vs. 0.575, P = 0.031. Analysis of the validation cohort showed similar findings for EPE (AUC 0.764 vs. 0.729, P = 0.13), SVI (AUC 0.819 vs. 0.749, P = 0.01), LNI (AUC 0.939 vs. 0.867, P = 0.02), and PSM (AUC 0.624 vs. 0.547, P = 0.04). Patients with WGGG >30 (high-risk group) demonstrated ∼50% failure at 2 years in both cohorts. Conclusions: The WGGG, by providing a metric reflecting the entirety of the PBx, is more informative than conventional single GGG alone in identifying adverse pathologic outcomes and risk of BCR following RP. This superior discriminatory capability has been achieved without any consideration of other commonly available clinical disease characteristics.