Gleason score 5 + 3 = 8 (grade group 4) prostate cancer-a rare occurrence with contemporary grading

Grade Group (GG) 4 prostate cancer includes Gleason scores (GS) 3 + 5 = 8, 4 + 4 = 8, and 5 + 3 = 8. Some studies without pathology re-review of historical cohorts proposed that the presence of pattern 5 worsens prognosis compared to GS 4 + 4 = 8 cancer. We assessed how often historically graded GS 5 + 3 = 8 cancers retain this grade with contemporary grading recommendations. Sixteen prostate biopsies and 24 radical prostatectomies (RP) reported from 2005 to 2019 as GS 5 + 3 = 8 were re-reviewed and graded according to contemporary recommendations. In discrepant cases, an attempt was made to explain the different grading. One (6%) biopsy and 3 (12%) RPs remained GS 5 + 3 = 8 (GG4) after re-review. Two (12%) biopsies remained GG4 but were re-graded as GS 3 + 5 = 8 and 1 (4%) RP was reclassified as GS 4 + 4 = 8 (GG4). Eight (50%) biopsies and 15 (64%) RPs were upgraded to Gleason scores 9-10 (GG5). Five (32%) biopsies and 1 (4%) RPs were downgraded to Gleason score 7 (GG2 and 3). One (4%) RP showed GS 3 + 3 = 6 (GG1) cancer. Data from 2013-current from the 3 institutions were available to assess the incidence of GS 5 + 3 = 8 following re-review of the cases. Out of 14 359 biopsies with cancer and 6727 radical prostatectomy specimens, only 1 case (0.007%) and no cases (0%) were graded as GS 5 + 3 = 8, respectively. Reasons for grading discrepancies included: 1) assigning an overall common grade to separate needle cores or tumor nodules; 2) inclusion of <5% lower grade pattern into grading; and 3) misinterpretation of variant histology and patterns. Challenging patterns were poorly-formed glands, signet ring cell-like features, atrophic carcinoma, ductal carcinoma, and mucinous fibroplasia. GS 5 + 3 = 8 (GG4) cancer is very rare with contemporary grading. The reliability of conclusions from retrospective databases regarding the clinical significance of this grade combination without slide re-review is questionable.