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There is disagreement in the medical community about a proposal to relabel prostate cancer Gleason score 6 (GS6) as non-cancerous, as detailed by recent commentaries in the (JCO).

Opponents argue that GS6 is still cancer, both histologically and molecularly, and that substantial numbers of patients are found to have higher-grade cancer on subsequent examinations. Reclassification, therefore, those experts say, could make patients less likely to follow up with active surveillance.

Proponents, on the other hand, argue that GS6 behaves like pre-cancer, not cancer, and that reclassification will dramatically reduce overdiagnosis and overtreatment, cut healthcare costs, and lessen patient anxiety.

In the following interview, Jonathan Epstein, MD, professor of Pathology, Oncology and Urology at Johns Hopkins School of Medicine in Baltimore and co-author (with Adam Kibel, MD) of the JCO "Comments and Controversies" article against re-classification to non-cancer -- "A Flawed Idea Scientifically and for Patient Care" -- discussed these arguments and issues.

What is the strongest argument against re-labeling GS6 as non-cancerous, if you had to pick one?

Epstein: Removing the label of cancer in men with GS6 cancer on biopsy could make it challenging to ensure they are carefully followed and biopsied sequentially during years of follow-up on active surveillance.

What do you think is the strongest argument on the other side for making this change, and how would you respond to it?

Epstein: Removing the cancer label from GS6 will decrease the fear of being diagnosed with cancer and will lessen overtreatment of indolent prostate cancer.

The argument to change GS6 to non-cancer based on the fear of cancer leading to overtreatment has also weakened as increasingly patients have demonstrated that they are more comfortable adopting active surveillance for GS6 prostate cancer.

How is GS6 like cancer histologically and molecularly?

Epstein: GS6 is cancer and often looks like higher-grade prostate cancer microscopically, and is invasive with a lack of basal cells, infiltration into the prostatic stroma, frequent perineural invasion, and uncommonly, even show extraprostatic extension.

Molecularly, GG1 has many adverse findings seen with the same frequency as in higher-grade prostate cancer. These include ERG rearrangements, recurrent point mutations and small insertions and deletions, and somatic DNA methylation of CpG islands within the GSTP1 gene.

What would it take to settle this controversy for good?

Epstein: Increasing adoption of active surveillance by both patients and urologists in the United States for GS6 to the same level it has happened in Canada and many countries in Europe.

Is there anything else you would like to add or make sure oncologists understand about this issue?

Epstein: One of the major arguments in support of keeping GS6's designation as cancer is that approximately 20% to 35% of these tumors on prostate biopsy are upgraded at radical prostatectomy, and even with imaging and other ancillary tests it is not possible to determine if a patient has pure GS6 cancer.

Read the commentary here.

Next time: Scott Eggener, MD, director of the High Risk and Advanced Prostate Cancer Clinic at the University of Chicago, makes the case for reclassification.