The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer

Abstract

Context.— Controversies and uncertainty persist in prostate cancer grading. Objective.— To update grading recommendations. Data Sources.— Critical review of the literature along with pathology and clinician surveys. Conclusions.— Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace “tertiary grade pattern” in radical prostatectomy (RP) with “minor tertiary pattern 5 (TP5),” and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) “atypical intraductal proliferation (AIP)” is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

Prostate cancer growth patterns beyond the Gleason score: entering a new era of comprehensive tumour grading

“…23 On the other hand, the Genitourinary Pathology Society (GUPS) recommends not factoring IDC into Gleason grading, and performing basal cell immunohistochemistry if classification as either invasive carcinoma or IDC would lead to a change in the final Gleason score. 26 Thus, a Gleason score 6 prostate cancer biopsy with a cribriform lesion is now classified as Grade Group 2 according to the 2019 ISUP recommendation, without immunohistochemistry; the GUPS recommends performing basal cell immunohistochemistry and grading the tumour as Grade Group 1 if basal cells are present and as Grade Group 2 if they are not. Both the ISUP and the GUPS recommend including a comment on the association of IDC with aggressive disease, whereas the vast majority of genitourinary pathologists consider the above-mentioned case not to be eligible for active surveillance.…”

“…As IDC is an adverse pathological parameter, and difficult or even impossible to distinguish from invasive carcinoma even with the use of basal cell immunohistochemistry, it was recommended at the latest 2019 ISUP consensus meeting that IDC intermixed with invasive carcinoma should be assigned a Gleason grade based on its underlying growth pattern, as if it were invasive carcinoma 23 . On the other hand, the Genitourinary Pathology Society (GUPS) recommends not factoring IDC into Gleason grading, and performing basal cell immunohistochemistry if classification as either invasive carcinoma or IDC would lead to a change in the final Gleason score 26 . Thus, a Gleason score 6 prostate cancer biopsy with a cribriform lesion is now classified as Grade Group 2 according to the 2019 ISUP recommendation, without immunohistochemistry; the GUPS recommends performing basal cell immunohistochemistry and grading the tumour as Grade Group 1 if basal cells are present and as Grade Group 2 if they are not.…”

Head to head: should the intraductal component of invasive prostate cancer be graded?

“…Recently, two international organisations, the ISUP and the Genitourinary Pathology Society (GUPS), have published independent updates on prostate cancer grading. 6,7 Unfortunately, these have conflicting recommendations on the reporting of IDCP. Both recommend that isolated (pure) IDCP should not be graded.…”

Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category

“…Indeed, recent studies are also conflicting about the value of GPS in active surveillance populations; in one recent study, increased GPS was associated with increased risk of adverse pathology at prostatectomy and with biochemical recurrence,31 whereas in another recent study no statistically significant association of GPS with adverse pathology after initial active surveillance was seen 32. The 2019 Genitourinary Pathology Society guidelines33 states that additional studies of RNA-based assays in active surveillance populations are needed to justify their utility.The GPS test has only been available since 2013 and is designed to identify clinically low-risk patients that really are higher risk; these factors limited the number of patients who underwent prostatectomy and median follow-up was only 585 days. Also, theNCCN classification system changed during the study period, with GPS tests including a high-risk category and subcategorizing the intermediate category into intermediate favorable and unfavorable only since May 2017.…”