The International Society of Urological Pathology (ISUP) 2014 consensus meeting recommended a novel grade grouping for prostate cancer that included dividing Gleason score (GS) 7 into grade groups 2 (GS 3+4) and 3 (GS 4+3). This division of GS 7, essentially determined by the percent of Gleason pattern (GP) 4 (< or >50%), raises the question of whether a more exact quantification of the percent GP 4 within GS 7 will yield additional prognostic information. Modifications were also made by ISUP regarding the definition of GP 4, now including 4 main architectural types: cribriform, glomeruloid, poorly formed, and fused glands. This study was conducted to analyze the prognostic significance of the percent GP 4 and main architectural types of GP 4 according to the 2014 ISUP grading criteria in radical prostatectomies (RPs). The cohort included 585 RP cases of GS 6 (40.2%), 3+4 (49.0%), and 4+3 (10.8%) prostate cancers. Significantly different 5-year biochemical recurrence (BCR)-free survival rates were observed among GS 6 (99%, 95% confidence interval [CI]: 97%-100%), 3+4 (81%, 95% CI: 76%-86%), and 4+3 (60%, 95% CI: 45%-71%) cancers (P<0.01). Dividing the GP 4 percent into quartiles showed a 5-year BCR-free survival of 84% (95% CI: 78%-89%) for 1% to 20%, 74% (95% CI: 62%-83%) for 21% to 50%, 66% (95% CI: 50%-78%) for 51% to 70%, and 32% (95% CI: 9%-59%) for >70% (P<0.001). Among the GP 4 architectures, cribriform was the most prevalent (43.7%), and combination of architectures with cribriform present was more frequently observed in GS 4+3 (60.3%). Glomeruloid was mostly (67.1%) seen combined with other GP 4 architectures. Unlike the other GP 4 architectures, glomeruloid as the sole GP 4 was observed only as a secondary pattern (ie, 3+4). Among patients with GS 7 cancer, the presence of cribriform architecture was associated with decreased 5-year BCR-free survival when compared with GS 7 cancers without this architecture (68% vs. 85%, P<0.01), whereas the presence of glomeruloid architecture was associated with improved 5-year BCR-free survival when compared with GS 7 cancers without this architecture (87% vs. 75%, P=0.01). However, GS 7 disease having only the glomeruloid architecture had significantly lower 5-year BCR-free survival than GS 6 cancers (86% vs. 99%, P<0.01). Multivariable Cox proportional hazards regression model for factors associated with BCR among GS 7 cancers identified age (hazard ratio [HR] 0.95, P<0.01), preoperative prostate-specific antigen (HR 1.07, P<0.01), positive surgical margin (HR 2.70, P<0.01), percent of GP 4 (21% to 50% [HR 2.21], 51% to 70% [HR 2.59], >70% [HR 6.57], all P<0.01), presence of cribriform glands (HR 1.78, P=0.02), and presence of glomeruloid glands (HR 0.43, P=0.03) as independent predictors. In conclusion, our study shows that increments in percent of GP 4 correlate with increased risk for BCR supporting the ISUP recommendation of recording the percent of GP 4 in GS 7 prostate cancers at RP. However, additional larger studies are needed to establish the optimal inter...