The absolute volume of Gleason Pattern 4 on radical prostatectomy is more strongly associated with advanced stage and biochemical recurrence than Gleason grade groups

ISUP Grade-Group (GG) is based on the relative proportion of Gleason patterns 3 and 4. We investigated whether absolute pattern 4 volume is more strongly associated with advanced stage and biochemical recurrence than GG in patients with pattern 4 but not 5. Overall, 1171 men received radical prostatectomy. Advanced stage definitions were extra-prostatic extension (EPE) or seminal vesicle invasion (SVI) or nodal invasion (LNI), and SVI or LNI. We explored the association between pattern 4 volume and percentage, and GG with advanced stage and recurrence using logistic and Cox regressions. We examined whether incorporating pattern 4 percentage improved the accuracy of a model including pattern 4 volume, PSA, and cT-stage. Overall, 649, 381 and 141 patients had GG2, GG3, and GG4. EPE, SVI, and LNI were in 643, 84, and 57 men. For the EPE, SVI, or LNI outcome, pattern 4 volume showed higher discrimination (0.748) than ISUP (0.693) and pattern 4 percentage (0.724). Results were strengthened when outcome was SVI or LNI and excluded patients without nodal dissection. Pattern 4 volume showed higher discrimination for recurrence (0.705) than ISUP (0.675) or pattern 4 percentage (0.680). Pattern 3 volume did not increase discrimination when added to pattern 4. PSA levels were driven by pattern 4 volume, with pattern 3 and benign volumes having less impact. The total amount of pattern 4 provides superior prognostic information than the relative proportion of patterns 3 and 4. Further research should investigate the best pattern 4 quantification method.