I just read a terrific blog by a Chicago author, Howard Wolinsky, who has been on Active Surveillance for Wilensky 10 years. He has Gleason 3+3 prostate cancer—and is doing just fine! As he reflects on his own experience, he quotes from several experts in urologic surgery and clinical pathology. Spoiler alert: he articulates both sides of a debate that has disturbed the community of True Believers who insist that Gleason 3+3 disease needs to be treated with surgery or radiation simply because it’s “cancer.”

This belief, which has dominated the PCa world since the 1960s when Dr. Donald Gleason distinguished the stages of evolution from normal cells to dangerous PCa. The 5 grades identified by the Gleason score are based on the appearance, under a microscope, of cells on a scale from 1 to 5. Here is my simplified explanation of the scores assigned to biopsy samples are examined under a microscope:

Grade 1 – All prostate cells appear normal, healthy, and organized
Grade 2 – Space is developing between the healthy cells
Grade 3 – Small clumps of early cancer cells are infiltrating and disorganizing the spaces
Grade 4 – Irregular masses of cancer cells are taking over, with few healthy cells present
Grade 5 – Complete disorganization, with sheets of cancer cells

Since the original Gleason score is reported as the sum of two numbers, the higher the sum, the greater the risk level. However, it confuses patients, especially because a PCa diagnosis begins at the middle score, with 3+3. Have you ever heard of Gleason 1+1, 1+2, 2+1, 2+2, 2+3 or 3+2? No, because such small scores do not mean cancer.

So why does Gleason 3+3 mean cancer?

That’s the question raised by Wolinsky. If we strictly interpret the original Gleason scores, a grade of 3 is given once cells that look like cancer are starting to appear, disrupting the structure of normal prostate tissue. Tucked into this score is the assumption that these early cancer cells will inevitably mutate into increasingly aggressive rogue cells.

This assumption may very well be “fake news.” The facts show otherwise. According to PCa expert Dr. Laurence Klotz, who is one of the earliest proponents of the notion that Gleason 3+3 is NOT cancer, we now know that “…Gleason 3 and Gleason 4 are like night and day, that the molecular genetics of most Gleason 3 is normal. The metastatic potential is approximately zero.”^[i]

This means that just because it looks like a cancer cell under the microscope doesn’t mean it behaves like a cancer cell. Most types of tumor cancers become more aggressive, eventually spreading to other organs and parts of the body. Klotz and others point to three cancers that are exceptions:

• Glioblastoma, a deadly brain cancer that infiltrates throughout the brain but does not metastasize beyond the brain
• Basal cell carcinoma, a common skin cancer that can grow but almost never metastasizes beyond itself
• Gleason 3+3 prostate cancer, in itself, has never been proven to metastasize.

Wolinsky quotes Dr. Scott Eggener of the University of Chicago:

In Gleason 6, it’s basically impossible to spread to other parts of the body. And there’s overwhelming evidence of that,” he said. “I am convinced there’s never been a man in the history of time who’s died from pure Gleason 6 prostate cancer. There’s never even been a case report of it, and for that reason I think men would be better served if Gleason 6 was downgraded…^[ii]

Serving patients’ needs

The last sentence in the above quote brings up the issue of patient needs. In the new Gleason Grade Group (GG) system, which is also a 5-point scale, 1 is the lowest grade group, and it is the equivalent of Gleason 3+3. If a man is told his biopsy came back positive but it’s only a Grade Group 1, it’s an immediate assurance that not only does he not have a life-threatening cancer, but that he’s a good candidate for Active Surveillance. This means he can maintain the lifestyle he currently enjoys, and use periodic monitoring (PSA blood tests and multiparametric MRI’s) to check in on his health status. Or, if he’s a more proactive person, he can begin integrating practices in nutrition, exercise and stress management that have been proven to boost immunity and further reduce PCa risk levels.

Wolinsky makes an additional point that I feel is important to highlight. He turns again to Laurence Klotz, “[Dr. Klotz] said about 2% of patients with low-grade Gleason 6 have serious genetic aberrations in their cancer cells, suggesting the cancers may be more aggressive. ‘It’s a small proportion but it’s not zero,’ he said. These cells probably mutate to a higher Gleason pattern before they metastasize.”^[iii]

I personally believe that Gleason 3+3 PCa is a unique category somewhere on the border between noncancer and cancer. It should not be ignored, but neither does it require the traditional push into radical treatments like surgery or radiation. While some clinicians have suggested relabeling it (e.g., incidentaloma or indolentoma^[iv]), patients diagnosed with Grade Group 1 who are not immediately enthusiastic about Active Surveillance may request a genomic analysis to rule out the presence of high risk gene mutation like BRCA1, BRCA2 or others. If no molecular red flag is present, an informed discussion on both Active Surveillance and a focal therapy like Focal Laser Ablation can offer reassuring alternatives to radical treatment.

I want to give a shout out to Mr. Wolinsky for sharing his personal journey, and to the experts he contacted who graciously consented to be interviewed. His own article serves patient needs very well.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Klotz, L. “Active Surveillance: Who is the Right Patient and What is the Right Protocol?” Grand Rounds Urology, Mar. 2017. https://grandroundsinurology.com/active-surveillance-right-patient-right-protocol/
[ii] Wolinsky, H. “Is This Really Cancer?” MedPage Today, Jan. 9, 2021.
[iii] Ibid.
[iv] Ibid.