#SUO14 - Session Highlights: Histology vs. genomics: Does Gleason 3 have the hallmarks of cancer?

BETHESDA, MD USA (UroToday.com) - In this exciting debate, Dr. Jonathan Epstein from Johns Hopkins argued that Gleason score (GS) 3 does have the hallmark of prostate cancer and should be called so, and Dr. Mark Rubin from Weill Cornell Medical College argued that Gleason 3 does not.

Dr. Epstein argues that pathologically and cytologically Gleason 3 looks like prostate cancer. There is a loss of basal cells which are cytologically indistinguishable from higher-grade cancer. They can be architecturally infiltrative like cancer and can have perineural invasion and extra-prostatic extension. Additionally, GS 6 exists on a molecular continuum with higher-grade cancer. About 5% of GS 6 have PTEN loss. ERG genetic rearrangement is equally common in GS6 as GS 7+ prostate cancers. Relative risk of GS 8-10 vs GS 6 for ERG-positive tumors is identical.

suoDr. Epstein is opposed to calling pattern 3 tumors “IDLE tumors” or “PNLMP”. This leads to improper nomenclature of possibly more aggressive cancers, such as calling GS 3+4 cancers containing an IDLE tumor and cancer. Dr. Epstein argues that upgrading of GS 6 on radical prostatectomy happens in about 20% of patients. If we do not call it cancer, there will be a significant number of men who will be missed and can progress. Rather, Dr. Epstein argues that there is a need for public education about GS 6. Patients should be counseled that they have a very good type of cancer and that they have to be followed closely. Prior to patient education, there needs to be a buy-in from the urologist into the concept of “good cancer.” Dr. Epstein is optimistic that more and more patients are asking today about active surveillance than few years ago. However, he emphasizes that there is too much confusion regarding risk-stratifying Gleason grades. Patients know that GS cancers go from 2 to 10. Thus, GS 6, to patients, is a middle-range cancer. Dr. Epstein proposed an alternative staging system, which is as follows:

GS 2-6 Grade 1/5
GS 3+4 Grade 2/5
GS 4+3 Grade 3/5
GS 4+4 Grade 4/5
GS 9-10 Grade 5/5


In their meta-analysis, progression free survivals are statistically significant at each grade. Therefore, Dr. Epstein argues that there is no need to change calling GS 6 cancer, but there needs to be an emphasis in patient education and the stratification of Gleason scores to make it easy for patients to understand the disease.

Subsequently, Dr. Rubin argued that “nothing in life has zero risk.” Calling GS 6 IDLE or PNLMP has low-risk. Multi-institutional study from Epstein showed only 3% risk of GS 6 progression. Additionally, biochemical recurrence after prostatectomy for GS 6 cancers is very low. GS 6 tumors do not metastasis to the LN. Prostate-cancer specific mortality in GS 6 is also very low in those who are treated with prostatectomy or those who are on watchful waiting.

On a molecular level, GS 6 is molecularly distinct. They have some genetic alterations, but no driving genetic changes such as gain of chromosome 8. They are much more homogeneous than GS 8 tumors. The Cancer Genome Atlas (TCGA) shows that the majority of GS 6 tumors are clonal as opposed to GS 8, which are more heterogeneous. Dr. Rubin summarizes that there is a need to unlink diagnosis of cancer from treatment. There is a need to develop risk-based diagnosis that also incorporates genomic data (risk modulators), and a need to develop molecular imaging modalities.

Overall, the session highlighted the low risk of GS 6 prostate cancer and a need for patient education and physician counseling to minimize over-treatment.

Presented by:
Jonathan I. Epstein, MDa and Mark A. Rubin, MDb
aJohns Hopkins Medical Institutions; bWeill Cornell Medical College

Moderated by:
Laurence H. Klotz, MD
Sunnybrook Health Sciences Centre 

Reported by:
Mohammed Haseebuddin, MD
* from the 2014 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 3 - 5, 2014 - Bethesda, MD USA

*Fox Chase Cancer Center, Philadelphia, PA USA



Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.