The debate over whether Gleason 6 should be called a cancer, a noncancer, or a precancer, is an old one. But my former urologist, Scott Eggener, MD, of the University of Chicago, reignited it.
In MedPageToday in January 2021, I unofficially kicked off what has become an intense debate about Eggener’s proposal to persuade doctors to reclassify Gleason as a noncancer. He argued that Gleason 6 (AKA Gleason Grade Group 1) “cancers” look like cancer but don’t act like cancers. He said “pure” Gleason 6 lesions pose no medical threat to patients, but they do pose risks for psychological and economic harms.
As a veteran journalist, I was trained not to pick sides. But this time, as a patient, an activist and advocate for patients diagnosed with Gleason 6, I saw no choice.
Here’s why: Nearly 13 years ago, a urologist tried to talk me into a “cure” with a prostatectomy of a tiny speck of Gleason 6. He didn’t support Active Surveillance (AS). Few urologists did in those days.
He was offering me unnecessary surgery with risks for impotence and incontinence. A crazy bargain that too many American patients accept to this day.
Only 6-10% of us had the cojones to go on AS in 2010 when I was diagnosed, compared with 60% in 2021. That’s still too high.
Compare the rate to Sweden, where 94% of low-risk Gleason 6 patients go on AS. “Socialized medicine” isn’t making them do it—as some U.S. doctors believe.
In the state of Michigan’s MUSIC program, 91% of those with low-risk disease go on AS. Last I checked, Michigan is still part of the U.S. of A.
So in 2010, I got a second opinion from Eggener. He called me the “poster child” for AS and predicted my cancer wouldn’t grow in the next decade. It didn’t.
Last year, Eggener asked me to join him and Drs. Alejandro Berlin, Matthew Cooperberg, Gladell Paner, and Andrew Vickers co-authored an article in April in the Journal of Clinical Oncology: “Low-Grade Prostate Cancer: Time to Stop Calling It Cancer.” The paper had legs.
The Eggener 6’s article was the most mentioned in the Journal of Clinical Oncology in 2022. The article was cited in the prestigious New England of Medicine. (At last. My first footnote in NEJM. Made my day.)
(Vickers, Cooperberg and Eggener just published a great summary of the debate, “Removing the Designation of Cancer from Grade Group 1 Disease Will Do More Good than Harm,” in European Urology. Check it out. There is more discussion about this throughout TheActiveSurveillor.com)
Let’s switch over to a videocast from Australia where a debate was held on these issues on “GU Cast, a podcast/vidcast by Declan Murphy, MD, director of Genitourinary (GU) Oncology, and Director of Robotic Surgery at the Peter MacCallum Cancer Centre, Melbourne, Australia, and his colleague Renu Eapen, MD.
It’s a fun program, if you consider its mission of covering cancers of the prostate, bladder, penis and the like to be fun. They do their best with the material that they’ve been handed.
A recent episode, entitled “Gleason 6 prostate cancer | Why we should rename it (and why we can’t)!” should be interest to readers of TheActiveSurveillor.com. Check it out.
I’ll give a summary here:
The program featured Scott Eggener, MD, of UChicago, and Matthew Cooperberg MD, MPH, of UCSF, advocates for redesignating Gleason 6 as a noncancer to relieve patients of emotional distress and financial toxicity. They favor “rebranding” Gleason GG1 “cancer” as a noncancer or a precancer. Dr. Eva Compérat, chair of uropathology at the Medical University of Vienna, presented the opposing side.
Murphy praised Eggener, a first-time guest on the show, for his efforts to end overdiagnosis and overtreatment of low-risk Gleason 6.
If you read nothing else, read and contemplate Eggener’s summary statement:
“I am absolutely convinced, based on loads of data, that public health would be better if we did not call it cancer. And for that reason, I, and many others, think it’s an important conversation that we should have within the prostate cancer community.
“It’s an unassailable truth that Grade Group 1 is literally incapable of causing symptoms, spreading to other parts of the body, and I would argue there’s not a man in history who’s ever died from it, or had severe local symptoms.
“And we should acknowledge that over the last decade or so all the new tools that we have available, we’re trying not to diagnose men with Grade Group 1. One of the great attributes of MRI is we don’t see it and don’t find it as much, with all of our screening biomarkers, even some of the genomic tests. So we’re pushing the argument out there just to have the conversation. It’s a healthy, important conversation for all the prostate cancer community to have.”
Cooperberg said he thinks the nature of the debate today has changed from years ago: “It does feel though this time that there’s a little bit more momentum. This conversation has not sort of died with the publication (of the article in the Journal of Clinical Oncology). It’s ongoing, and I think there’s some sense that we’re on the right side of history here, and eventually, there’s going to be a change.”
Eggener cited a survey in which he was involved of 1,300 doctors in a variety of medical specialties. “We were surprised to see about half total were interested in either considering a name change and didn’t categorically refuse it,” he said.
This is a benchmark for what he hopes will be the change ahead.
The Active Surveillor, AnCan’s Virtual Support Group for Active Surveillance, Active Surveillance Patients International, and Prostate Cancer Support Canada, conducted a survey of more than 450 patients on or formerly on AS. 35% each favored or opposed a name change. Only 5% said they would drop surveillance if the cancer diagnosis would be ekiminated. More than 80% said they would continue on surveillance. For more on this, go to:
Meanwhile, Eggener said two physician groups were most opposed to reclassifying Gleason 6: pathologists and older urologists.
No surprise: Reading prostate biopsy slides are a bread-and-butter issue for pathologists. And urology, like other medical specialties, changes slowly.
Murphy mentioned how explosive the word “cancer” is when a patient receives the diagnosis. The doctors may say you have “low-risk prostate cancer.” I can attest that most of us only hear the “C-word.”
Murphy said, “The word ‘cancer’ has a very specific and highly adverse emotional resonance, which is true, amongst a lot of our patients, most of our patients.”
(He then gave me a shout-out. He said to Eggener: “Your patient Howard Wolinsky writes very eloquently about that, and we’ll put some links to his stuff.”
(Thanks, Declan. Every little bit helps, right? BTW, my emotional discomfort in my so-called “cancer journey” was minor and brief, mainly while waiting six months for a follow-up biopsy after a first, ambiguous biopsy. My main personal gripe is financial toxicity from a term life insurance policy being canceled, and my rates hiked over what my doctor considered to be a harmless cancer diagnosis.)
Cooperberg said: “The term ‘cancer’ predates modern pathology by millennia, literally it goes to the time of Hippocrates. And that resonance with the public is not going away anytime soon. The word has implications and has a certain connotation that has nothing to do with the way it looks under the microscope. And I think these days we’re understanding more and more about these different lesions at the molecular level and at the clinical level that goes beyond histologic appearance. So, in terms of what we should be called cancer, this is a debate that goes beyond prostate cancer.”
Compérat said there is a cultural component clouding the issue–European patients more readily accept the concept of Gleason Grade Group 1 and active surveillance—living with prostate cancer and not dying from it– than do Americans.
I think, in part it’s how doctors Gleason 6. Patients may be scared into making irreversible decisions that can harm them physically, psychologically, and emotionally.
Swedish urologist Dr. Ola Bratt, one of the fathers of AS in Europe, says he tells patients that they have cancer that doesn’t need to be treated. Rather, than saying, you have cancer.
Likewise, Laurence Klotz, MD, the Canadian AS pioneer, says he talks patients off the ledge by telling them they have a pseudo-cancer, a cancer imposter.
Compérat explained that a prostate cancer diagnosis is made under the microscope based on the appearance of cells. Pathologists look for irregularities in cells and the proportion of these irregularities among cells on biopsy slides as they appear under the microscope.
(Gleason 6 cells.)
She said: “As long as you just have a biopsy, you just have a part of the sample.”
In other words, pathologists can’t examine the whole gland with a biopsy. A compleat study would take a prostatectomy, which you hopefully can avoid. So there are lots of questions about what lurks inside that prostate cancer or outside it that biopsies don’t sample.
Pathologists get a dozen to two dozen or so slides. (Fun fact: It would take 10,000 samples to sample the entire prostate.)
We don’t know what’s lurking elsewhere in the prostate. I know a guy with a low-volume Gleason 6 who appeared to be a perfect candidate for AS. But he had a risky family history with the BRCA2 variant, which predicts trouble ahead. He underwent a prostatectomy. The pathologists found he had advanced cells hidden away in his prostate.
So you need to get MRIs, PSAs, DNA tests of your family inheritance, and genomic tests of your tumor if biopsied.
But a “pure” Gleason 6 never causes problems. The problem is finding them.
Compérat teased her colleagues when she asked if they would call a Gleason 6 lesion with a BRCA mutation noncancerous.
“I know you would. But I wouldn’t,” she joked.
Following a biopsy, she said, “It’s up to you clinicians to say, well, this is a cancer, but it’s not a very, very big issue. But it’s more a problem of explanation to the patients, in my opinion, especially to the Americans.”
I think AS needs more urologist buy-in and better selection of patients for AS and treatment.
Murphy asked whether Eggener was going to give up on the idea of dropping “cancer” in Gleason 6. Eggener has told me he is playing the long game, making this a career objective.
Murphy said: “I personally feel we’re going to struggle with that even with really, really clinically astute people like many of these GU pathologists like Eva are. They’ll say, yeah, yeah, but it’s still cancer.
Eggener responded, “I’m hopeful and confident and admittedly biased that we’ll get there because I think it’s the right thing to do. But what Eva said is absolutely correct. In 2022, by current histologic [histology being the study of cell structure by micoscope] criteria, it meets the definition of cancer. But that is a histologic and, subsequently, a social construct of where we draw the line of what we call cancer or not. And it has massive implications for public health, and not in a good way.
“And if you just take a step back on a macro level and look at any dictionary definition of benign vs. malignant, basically benign versus cancer. Cancer is something that can replicate endlessly, spread, cause pain, cause death. Gleason 6 does not meet that definition. Genetically, molecularly, there are precancerous lesions that share characteristics with Grade Group 1, Grade Group 2, Grade Group 3. We don’t call those cancer. There’s a lot of men walking around with Grade Group 2 or higher. We screen them. They’ve had a previously negative biopsy. They may have Grade Group 1.”
Eggener said he recently asked a group of doctors attending a conference if they would want to know if a loved one had Gleason 6 cells.
“Not a single person raised their hand. And we know for men over the age of 50, roughly, 30 to 50% of them are walking around with prostate cancer. And anyone who knows anything about clinical prostate cancer probably doesn’t want to know about it,” he said.
I think about this often: If I were screened today, based on MRIs and genomic and DNA tests, I probably would never have been diagnosed and would not be writing this newsletter. Fate played a trick on me and my “wimpy” so-called “cancer.”