Time to stop calling Gleason 6 cancer? Time to call it 'acinar neoplasm'?

Will 'acinar neoplasm' fly as a new name for Gleason 6? Or is that just asinine?

By Howard Wolinsky

In February 2023, a group of leaders in prostate cancer gathered offsite during the American Society of Clinical Oncology meeting in San Francisco to discuss whether Grade Group 1 (GG1) (Gleason 6) low-grade prostate cancer should be renamed as a non-cancer.

The meeting proceedings were just published in the Journal of the National Cancer Institute under the title: When is prostate cancer really cancer?”

Not everyone agreed Gleason 6 should be renamed a noncancer. But there was a consensus to discuss the issue and see where the debate leads.

Lead author Matthew Cooperberg, MD, MPH, of the University of Califorbia, San Francisco, an advocate for renaming GG 1, said: “As a start, agreeing that what we now call GG1 cancer has an extremely favorable natural history can shape future conversations, practice, and policy. Many believe the public health benefits of a nomenclature change would far outweigh any adverse consequences while others raised concerns regarding the rationale, implementation, pathologist variability, and patient-focused implications.”

The Times of London put more of a positive spin on changing the name:

Tom Whipple, science editor of The Times, explained: “Referring to the lowest grade of prostate cancer as ‘cance;” could be causing more harm than good, scientists have said. Instead, an international symposium of experts has recommended that the commonest cellular abnormalities, which sometimes become aggressive but most often do not, should be given another name to avoid unnecessary worry, stigma and medical interventions.”

Speakers came from Harvard, Memorial Sloan Kettering, Fred Hutch Cancer Center, University of Chicago, University of Toronto, Dana Farber, National Cancer Institute, Prostate Cancer Foundation, Peter MacCallum Cancer Centre, Imperial College London, MD Anderson, University of Michigan, etc.

There was aWho’s Who of prostate cancer research. And me.

“The word ‘cancer’ has resonated with patients for millennia as a condition associated with metastasis and mortality,” said Cooperberg.

He and his colleagues wrote that the level of low-risk prostate cancer was “so common in aging males as to be perhaps a normal aspect of aging”.

He said these lesions “in some cases presage development of aggressive cancer but in most do not. We absolutely need to monitor these abnormalities, but patients should not be burdened with a cancer diagnosis if what we see has zero capacity to spread or to kill.”

The summit included stakeholders with expertise in prostate pathology; urologic, medical, and radiation oncology; translational and population science; epidemiology and biostatistics; and primary care, along with breast and thyroid cancer specialists; patients; and leaders from federal, policy, and advocacy organizations.

Many doctors worry that if Gleason 6 were renamed a noncancer that patients would abandon surveillance, which could put their lives at risk. .

Cooperberg noted: “Participants speculated that absent a cancer diagnosis, patients may not take surveillance seriously and some cancers may progress undetected. However, preliminary survey data suggest very few would actually stop AS given a name change, and others noted that large randomized trials have failed to show increased mortality for GG1 even in the absence of any organized surveillance.

On the other hand, he noted: “… a nomenclature change would eliminate the stress and anxiety of cancer diagnosis, further reduce treatment rates, and hopefully obviate the persistent problem of US GG1 patients being denied or overcharged for life or health insurance policies.

One summit participant “stressed the importance of dialog across stakeholders, including engagement with public opinion. A universal consensus among our participants was the imperative of ongoing conversation between pathologists and clinicians.”

Both specvialties have a lot at stake in defining this. And so do we patients.

I represented The Active Surveillor and the AnCan Foundation and shared a survey of 460 patients, which addressed some important issues. (Several other patient organizations also participated in the survey.)

We found that only 5% of men on AS would stop surveillance if Gleason 6 were no longer called cancer while 82% would continue and the remainder were undecided.

For more:

Cooperberg et al. noted: “Patient perspectives highlighted the adverse effects of overtreatment and the burden of a cancer diagnosis. The anticipated impact on screening and treatment varies across healthcare systems, but many felt public health would on balance greatly improve if GG1—along with lesions in other organs with no capacity to cause symptoms or threaten life—were labeled something other than ‘cancer.’ Ultimately, the goal is to reduce PC mortality while minimizing harms associated with overdiagnosis and overtreatment.”

They added: “Patient participants shared the well-recognized and often profound adverse effects of overtreatment of GG1, but also surfaced the less-discussed social, psychological, and financial implications of a cancer diagnosis to patients, their families, and caregivers, even in the absence of explicit overtreatment.”

(Several of the leaders and I wrote “Low-Grade Prostate Cancer: Time to Stop Calling It Cancer,” addressing these issues in the Journal of Clinical Oncology in 2022: https://ascopubs.org/doi/full/10.1200/JCO.22.00123)

Cooperberg noted: “In autopsy series, histologic GG1 is so highly prevalent it might be considered a normal feature of aging. When pure GG1 is present, it cannot cause symptoms or metastasize.  Overdiagnosis and overtreatment of GG1 have historically been ubiquitous, driving excessive and avoidable morbidity without substantial survival benefit.

“Contemporary diagnostic pathways use imaging and biomarker tests for patients with elevated prostate specific antigen (PSA) levels, with the explicit goal of identifying higher grade disease (GG≥2) and avoiding biopsy if this likely result is either benign or GG1. Thus GG1 has effectively become an inadvertent diagnosis, incidental to the goal of the identifying clinically significant disease. In some cases GG1 is a marker for the concomitant or future presence of higher grade cancer, and all meeting participants agreed that, regardless of nomenclature, GG1 should nearly always be managed with initial active surveillance (AS) or observation, concordant with international guidelines. Occasional exceptions would apply as today to justify immediate treatment—for example for men with strong family history of early lethal disease.

“For most men, though, were the name changed, AS should not be de-intensified relative to current protocols. In the US, rates of AS for GG1 have been rising, but as of 2021 over 40% of GG1 cancers are still treated immediately, with drastic local variation. Summit participants noted that frequency of AS use likewise varies globally, with near universal adoption in some systems, heterogeneity similar to the US in others, and unquantified utilization in many.”

Video presentations and discussion can be found at this link: https://www.urotoday.com/video-lectures/cancer-or-not-cancer-evaluating-and-reconsidering-gg1-prostate-cancer-cancer-gg1.html.

During my 240-second spiel, I pointed out the survey did not get an adequate response from Black men and Latinos. This defect was an important turn.

A researcher from the Centers for Disease Control and Prevention called me afterward and asked if I’d like to “refield” the survey and include more minority men. I said yes, and in the end we got $1 million for a three-year study. We just started the research led by Cooperberg. Stay tuned.

Grade Group 1: Don’t call it normal

By Howard Wolinsky

Participants in the 2023 symposium (above) agreed that GG1 should not be presented to patients as “normal.”

But there was no consensus regarding alternative labels or their likelihood in garnering support among pathologists, though Matthew Cooperberg, MD, of the University of California, San Francisco, one the leads io the program, said “acinar neoplasm” generally has the broadest support.

Really Could you see being diagnosed with an “acinar neoplasm”?

(FYI, acinar prostate refers to the acinar epithelium, a layer of cells that line the prostate gland that is involved in the development of prostatic acinar adenocarcinoma (PAC), the most common type of prostate cancer:)

I think they need to work on that one. Acinar may do the trick for pathologists and urologists even. What about you? Is acinar asinine?