Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade

Abstract

Background The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear. Objective To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction. Patients and Methods We conducted a case–control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998–2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC). Results The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS. Conclusion The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.

Impact of comedonecrosis on prostate cancer outcome: a systematic review

“…a group of cells with clear karyorrhexis, pyknosis, cytoplasmic condensation, and accompanying eosinophilic necrotic debris present in cribriform or solid invasive adenocarcinoma 15 . Nine studies were on radical prostatectomy specimens, 14–16,18,20–22,24,25 two on biopsies, 19,23 and one on both specimen types 17 . Ten studies explicitly stated they used whole slides for review 14–19,22–25 .…”

“…The 2016 World Health Organisation (WHO), 2014 and 2019 ISUP recommendations were used in all manuscripts on acinar adenocarcinoma, one on ductal adenocarcinoma and one on intraductal carcinoma (n = 8). [14][15][16][17][18][19][20][21] The remaining four manuscripts used either Epstein's (n = 2) 22,23 or McNeal's (n = 1) 24 criteria for IDC, while one report on comedonecrosis in ductal adenocarcinoma 25 did not specify formal diagnostic criteria. One study explicitly provided a definition of comedonecrosis, i.e.…”

“…17 Ten studies explicitly stated they used whole slides for review. [14][15][16][17][18][19][22][23][24][25] In nine studies, slides were reviewed by at least one pathologist 14,15,[18][19][20][21][22][23][24] who was explicitly blinded for clinical outcome in seven studies. 14,[18][19][20][21][22]24 In total, 4059 patients were included in the 12 studies, 410 of whom were reported to have comedonecrosis (Table 1).…”

“…15,17,21,24 Median time of follow-up was ≥ 12 months for eight studies and not specifically recorded for the other four. 14,18,19,21…”

“…studied 1064 patients with grade groups 1-5 PCa at radical prostatectomy, 32 of whom (3%) had comedonecrosis in invasive carcinoma. In the subgroup of grade group 5 tumours, 17 (14%) had comedonecrosis within invasive cribriform or solid Detailed overview of studies included in the systematic review on comedonecrosis PCa, Zelic et al19 found that comedonecrosis was present in 29 (4%) of biopsies. Comedonecrosis was present in 27 of 369 (7%) men who died of disease and 0.5% of controls.…”