With regards to percent Gleason 4, GUPS recommends reporting the percentage of Gleason pattern 4 in a needle biopsy with Grade Groups 2-3 (3+4=7 and 4+3=7). Additionally, GUPS recommends reporting the percentage of Gleason pattern 4 in the needle biopsy on parts with Gleason score 7, even if another part(s) in the case shows Gleason score 4+4=8. Reporting of the percentage of Gleason 4 on needle biopsy may have important clinical ramifications, particularly when considering a patient for active surveillance: 3+4=7 with <10% may be a candidate for active surveillance, whereas someone with 50% pattern 4 is likely not a candidate. When considering the percentage of pattern 4 for patients with 4+3=7, someone with 90% pattern 4 may be considered for radiotherapy +/- ADT (GG3 bordering on GG4), whereas 4+3 with 60% pattern 4 (GG3 bordering on GG2) would be considered for radiotherapy without ADT.
The second recommendation discusses tertiary grade patterns. New terminology “minor tertiary pattern 5” replaces tertiary grade pattern. GUPS does not recommend using tertiary on needle biopsies, but rather favoring pattern 5 as the secondary score when pattern 5 is present, ie:
For patients undergoing radical prostatectomy, three patterns (including minor tertiary pattern 5) should be used as necessary. Dr. Epstein notes the following points for the effect of minor tertiary pattern 5 on Grade Group:
- Some studies show that cases with tertiary pattern 5 behave similar to those in the next higher Grade Group (ie. Grade Group 2 with minor tertiary pattern 5 behaves similar to Grade Group 3)
- Other studies show a prognosis intermediate between grades (ie. Grade Group 2 with minor tertiary pattern 5) behaves intermediate between Grade Groups 2 and 3).
- As such, minor tertiary pattern 5 is noted along with the Gleason score, with the Grade Group based on the Gleason score (ie. Gleason score 3+4=7, GG2, with minor tertiary pattern 5)
With regards to MRI targeted biopsy, when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all of the involved cores were one long core. Furthermore, if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, pathologists should give a single global score (factoring both the systematic standard and the MRI-targeted positive cores).
Dr. Epstein also provided an update on Grade Groups, which were first proposed in 2013 by Dr. Epstein’s group at Johns Hopkins Hospital. Since then, the concept of Grade Groups has been endorsed but not developed by multiple societies. “Grade Group” nomenclature has been accepted by the American Joint Committee on Cancer (AJCC), College of American Pathologists (CAP), 2014 ISUP Consensus Conference, World Health Organization (WHO), and other international associations and organizations. One of the recommendations is to retain Gleason scores 3+5=8 and 5+3=8 as Grade Group 4, acknowledging this is a very rare event. In a large multi-institutional study including GU pathology experts, out of almost 21,000 radical prostatectomy specimens, there were only 0.2% of cases with Gleason score 3+5=8 and only 0.02% with Gleason score 5+3=8. Furthermore, out of over 16,000 needle biopsy cases, there were only 0.3% of cases with Gleason score 3+5=8 and only 0.04% with Gleason score 5+3=8. In the few studies that have assessed Gleason score 3+5=8, there appears to be a similar prognosis to Gleason score 4+4=8. However, Dr. Epstein notes that it is less clear at this point in large part due to its rarity, whether Gleason score 5+3=8 should be more appropriately categorized as Grade Group 4 or 5. Importantly, by keeping the Gleason score along with the Grade Group, clinicians can subcategorize Gleason score 8 into cases with or without Gleason pattern 5 when stratifying patients into randomized trials.
With regards to cribriform carcinoma, Dr. Epstein states that the vast majority of studies in prostate cancer with cribriform architecture, whether inclusive of intraductal carcinoma or not, demonstrate associations between these prostate cancers and both adverse clinical outcomes and molecular features typically seen in advanced disease. Based on these findings, GUPS recommends reporting the presence or absence of cribriform glands in biopsy and radical prostatectomy specimens with Gleason pattern 4 prostate cancer. Dr. Epstein notes that there are several significant issues with some of the studies on cribriform glands:
- Different definitions as to what constitutes adverse morphology in cases with cribriform glands (ie. large versus small versus any cribriform; definition of large cribriform)
- Non-contemporary patient populations sampled by sextant (6-core) biopsies
- Not distinguishing between intraductal carcinoma and cribriform carcinoma
For intraductal carcinoma, Dr. Epstein suggests utilizing the criteria proposed by Guo and Epstein in 2006.2 This includes reporting the presence of intraductal carcinoma in biopsy and radical prostatectomy specimens. Furthermore, when intraductal carcinoma is identified on prostate biopsy without concomitant invasive adenocarcinoma, it is important to add a comment stating that intraductal carcinoma is usually associated with high-grade prostate cancer.
Dr. Epstein concluded with several summary points for his presentation:
- Controversies and uncertainty persist in prostate cancer grading
- The first prostate cancer grading recommendations from GUPS addresses these areas
- These recommendations on contemporary prostate cancer grading will be the basis of more standardized reporting while stimulating new avenues of research
Presented by: Johnathan Epstein, MD, The Reinhard Professor of Urologic Pathology, Professor of Pathology, Johns Hopkins Hospital, Baltimore, MD
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 12th European Multidisciplinary Congress on Urological Cancers (EMUC) (#EMUC20 ), November 13th - 14th, 2020
References:
- Epstein JI, Amin MB, Fine SW, et al. The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer. Arch Pathol Lab Med. 2020 June 26 [Epub ahead of print].
- Guo CC, Epstein JI. Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance. Mod Pathol. 2006 Dec;19(12):1528-1535.