My urologist, Brian Helfand, MD, often refers to my cancer as “lazy.” Others call this sort of low-risk Gleason 6 cancer “indolent.” Some doctors don’t even think it ought to be called cancer.

(Check out my article in MedPage, “Is this cancer?” (Free subscription with registration.)

Most of us low-risk prostate cancer patients—and we are the majority—will die from something other than cancer. The Big C gets our attention. Guys, we need to take care of our tickers.

In any case, Duke University researchers (Go “Blue Devils”) have identified a genomic signature that could lead to a test that could answer an important question for men like us: Who should undergo treatment early in their diagnosis vs. those who could safely postpone therapy, if any is needed at all.

We’ve heard of these “Holy Grails” before so we eagerly await great results by “"les Diables Bleus” in developing a test to help us avoid biopsies, MRIs, and above all, surgery and radiation. Maybe active surveillance will be unnecessary in the future if we get an all-clear. Time will tell.

Jiaoti Huang, M.D., Ph.D., chair of Duke’s Department of Pathology and a senior author of the study. published the study online in the journal European Urology.

“We performed single-cell RNA sequencing analysis of freshly isolated tumor cells from primary, untreated prostate cancers in men as well as advanced cancer cells,” said Huang,

“We discovered that a small fraction -- less than 0.5% -- of primary prostate cancer cells possess the genomic features of advanced and aggressive prostate cancer cells that have become resistant to hormonal therapies,” Huang said. “This shows that hormonal therapy resistance can be a feature present in a small number of tumor cells early in the disease process before therapy.”

(Jiaoti Huang, M.D., Ph.D. M.D., Ph.D.)

Huang said the goal now is to develop a clinical assay that identifies the more dangerous cells, which could trigger earlier, aggressive treatment in some patients to avoid disease progression.

The study received funding from the National Institutes of Health and the Prostate Cancer Foundation.

The Active Surveillor asked Huang some questions, which he graciously answered:

Can you summarize your findings?

We performed single-cell genomic analysis of primary prostate cancer cells and compared them with advanced, castration-resistant prostate cancer cells (CRPC cells), to obtain genomic signatures of the two biologically different cell types. However, when we analyzed individual cells, we discovered that there are rare CRPC –like cells in primary prostate cancer, indicating that resistance to hormonal therapy and biologically aggressive behavior is a feature already present in some primary tumor cells before treatment.

What does the mean for men with low-risk prostate disease?

If a prostate cancer that is histologically low- or intermediate-grade harbors a high number of these aggressive cells, cancer may be more malignant than we currently recognize and such patients may benefit from early, aggressive treatment.

Where is this research heading?

The research will help to stratify patients for optimal management. Patients who have truly indolent diseases can be safely monitored to avoid unnecessary side effects from radical therapies while those whose tumors contain more of these aggressive cells will benefit from early intervention to prevent disease progression.

What sort of new test could be developed from this? A way to stratify men who have hidden aggressive cells?

 We are hoping to develop an easy laboratory test that can be useful in identifying patients whose tumors appear low risk but harbor hidden aggressive cells.

Finally, I see you are a pathologist. There is a movement to reclassify Gleason 6 as a non-cancer. My friend Ming Zhou, MD Chair and Pathologist-in-Chief, Tufts Medical Center, said he supports this change. He changed his mind after this debate.

But his mentor, the famed Jonathan Epstein, MD, director of Surgical Pathology at The Johns Hopkins Hospital, another friend, says no way.

Where do you stand?

There are two different scenarios. For patients who have Gleason 6 tumors on biopsy, some may have more aggressive tumors that were missed by the biopsy needle. I still consider these patients to have cancer.

Our job is to stratify them into low risk (majority of the patients) and high risk (minority of the patients) groups for different management options. For patients whose prostatectomy specimens show only Gleason 6, organ-confined tumor, I consider them cured.

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