BACKGROUND: A new prostate cancer (PCa) grading system (namely, Gleason score-GS- ≤6 vs. 3+4 vs. 4+3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three-tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five-tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR). METHODS: Between 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan-Meier curves, multivariable Cox regression analyses, and concordance index (C-index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3+4 vs. 4+3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3+4 versus 4+3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n=1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications. RESULTS: Overall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3+4, 4+3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre- and post-treatment models, respectively. The C-index of the five-tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre- (range: 0.001-0.006) and post-treatment models (range: 0-0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five-tier GG system did not result into higher net-benefit relative to the other three Gleason grade classifications. CONCLUSIONS: The difference in accuracy between the five-tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five-tier GG system represents a simplified user-friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. © 2016 Wiley Periodicals, Inc.