Low grade PC should or should not be called Cancer

Should Gleason 6 be labeled as cancer?
(2016, Full Text, Dr. J. Epstein is a co-author)

"Conclusions/Summary
The case for removing the label of cancer is largely supported by the following: i) the negligible rate of lymph node metastases in men with GS6 disease in RPs; ii) the very low risk of progression after primary treatment in men with GS6 disease; iii) the general safety of AS and the very low rates of progression of men with GS6 disease in AS; and iv) the lack of convincing molecular pathological longitudinal evidence to date showing that a pure GS6 tumor can progress to a higher grade life threatening lesion over time. In our opinion, however, the arguments for the continuation of using the term cancer for these lesions still overshadow those against removing the label of cancer. For example, there are a number of histological and molecular features of GS6 tumors that support the label of cancer for these lesions and there is no solid molecular evidence suggesting that GS6 vs higher grade tumors commonly arise as unique and distinct molecular subtypes as in the case in other cancers such those in the breast and urinary bladder. In fact, a number of histopathological and molecular alterations are shared between GS6 and higher grade lesions such as nuclear alterations, invasion into the stroma, ETS family member gene fusion events, chromoplexy and somatic CpG hypermethylation of specific genes. While some of these changes are substantially less common in GS6 tumors, they nonetheless support similar pathways of tumor development overall. Further, given the practical issues with sampling leading to frequent under-grading with prostate needle biopsies, we submit that it would be pre-mature to remove the label of cancer from GS6 prostate tumors. Rather, we favor the application of new prognostic groups such that GS6 tumors fall into the lowest of these groups which will provide patients and clinicians with reassurance about the overall favorable prognosis of these tumors, without renaming the lesion to a non-cancerous entity at this time (3, 14).

The case to be made that pure Gleason score 6 (i.e. only Gleason pattern 3) tumors are not capable of causing significant harm in the vast majority of cases.

Yet, the issue of Gleason score 6 (pattern 3 only) lesions identified by today’s standard prostate needle biopsies to be associated with un-sampled higher grade tumor in up to 35% of cases greatly diminishes the force of the argument for removing the cancer label.

Further support for retaining the cancer label stems from molecular studies of heritable somatic genomic alterations (e.g. GSTP1 promoter hypermethylation, TMPRSS2-ERG fusion genes and chromoplexy) that suggest common molecular pathways for early lesion develop in Gleason pattern 3 and higher grade lesions."

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"Is This Really Cancer? — Movement builds to classify Gleason 6 prostate lesions as nonmalignant" (2021)

'He [Dr. L 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.'
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(1) As mentioned, as many as 35% of men who have a G6 biopsy are upgraded if they choose surgery because they harbor lesions >G6. In other words, they do have cancer even if you don't label G6 as such.

(2) Even among men who would have true G6 disease (that would be confirmed if they choose surgery) about 10% of them are nonetheless high risk for developing higher-grade lesions and mets within 5 years according to Decipher test results.

(3) Complacency and lax or no AS would likely increase among men who think "This isn't cancer--now I don't have to worry."

The correction for overtreating G6 is education (of doctors and patients) and proper AS, not redefining G6.

Djin

Post Edited (DjinTonic) : 4/20/2022 8:07:39 PM (GMT-6)

This comes up for debate every five to seven years. Same contentions with no real resolution for any change. The best statement in the article is that low risk does not mean no risk.

deja vu all over again

It's definitely cancer. IMO there is already too much effort to downplay the significance of this disease, to placate its victims and to keep them in the dark, so they can get a few more years of work out of them before becoming just another grumpy, incontinent old man. There should be a requirement when the PSA hits four to inform the patient that this could be cancer, rather than "it's nothing to be concerned about" that I got from both my GP and my urologist.

As it is, I feel like I'm a leper if I mention that I have had PCa. Women especially, liken it to nothing more serious than menopause. When I try to explain the significance of Gleason 8 or grade group 4 to anyone who might be interested, it's as though they're already thinking, well four is just one above three, and three isn't even cancer, right?

I grow weary of not being taken seriously, just because so many men end up with this disease eventually, and I'm not metastatic (not saying that I would want to be!) Difficulty peeing, bowel problems, and having no drive or interest is bad enough.

F8 said...
i associate the "it's not cancer" argument with not PSA testing younger guys because they be overtreated movement

The prostate snatchers and the resulting USPSTF "don't say cancer" recommendation of 2012 ended the era of early detection, which is why today, ten years later, we have more men presenting with advanced PCa. The recommendations were supposed to result in some sort of "shared decision making", yet it was four years after my PSA passed 4.0 before anyone ever even mentioned the word "cancer" to me.

Decision making isn't "shared" when only one party knows that what's going on might be cancer.

"A rose, by any other name, would smell as sweet."

The Important thing is the 35% number. Finding G6 is like finding a genetic abnormality highly suggestive of (but not guaranteed to get) Bad Cancer. That, coupled with the poor resolution of the biopsies, and there is a huge amount of uncertainty on what is actually going on in the prostate.

There is good work to be done and money to be made by coming up with a device that could go up the urethra and somehow sproing out into 50-60 samples of the prostate, each sub-millimeter in diameter.

I am having a HoLEP tomorrow for my BPH, which as an OBTW will also give a much better look at my prostate pathology. We will see what the biopsy may have missed.

alephnull said...
IMHO
It should be required that all biopsies be sent for a second opinion to a doctor outside of the practice.
If the second opinion agrees it's G6, then it should be classified as pre-cancerous.
Being pre-cancerous, AS would be the only treatment available UNLESS the abnormal cells are more than 25%(or some other % that is agreed upon by the medical community) of the prostate.
Then it would also be re-classified as cancer, and further treatment allowed.

1. You are not a candidate for standard AS programs and are advised to have primary treatment if you have a large number of G6 cores (fewer if they are bilateral), your PSA is high (usually >10), etc.

2. The decipher test has shown that about 10% of men with confirmed G6-only lesions are at high risk for developing higher-grade lesions that metastasize within 5 years. (Among the small number of G6 men whose cancer has grown into neighboring structures (bladder neck, EPE), this goes up to 16%.) Are you saying even these men should be denied treatment? That's not bad practice, it's malpractice.

3. Some men who are otherwise candidates for AS may want to have treatment for a number of reasons, including a strong family history, worry about disease progression, etc. Active surveillance cannot guarantee that you won't fall through the cracks and develop metastatic disease in the case your G6 progresses after a number of years, you leave AS and have treatment that proves unsuccessful. Roughly 50% of men are told to leave AS and seek treatment at some point because they no longer qualify. For some of those men, earlier treatment would have made a difference.

Even in dermatology, you are advised to have some pre-cancerous lesions removed. The same is true for the types of intestinal polyps that are pre-cancerous.

Djin

It should still be called cancer because they cannot rule out the presence of more aggressive cells with current technology.

There was a gentleman on another forum supposedly a G6 that was “organ confined”. He had radiation and thought he had won. He didn’t. It metastasized everywhere, including his brain.

Cancer is an odds game, but its still cancer.

We should not default to acting like an ostrich.

In response to the paper published in the Journal of Clinical Oncology about renaming low grade prostate cancer to something other than cancer I wrote this published rebuttal from the layman perspective. It should be noted that I agree with all points of the paper by Eggener et al. I feel it fell short of describing all actual patient experiences with regards to the "anguish" of a "Big C" diagnosis and was narrowed to point out only why it should be changed. If we only discuss with Active Surveillance patients that will never have to treat their disease, I'd agree with renaming. But because there is a est. 25% error in accurate diagnosis, and another 25% that change direction for various reasons I encourage education ahead of renaming to pre-cancer or something else. What's important is that regardless of the name, men must watch their diagnosis with determination to stay ware of the possibility of a bad turn somehwere down the line. Renaming could instill the belief that there's nothing to worry about. That would be a mistake.

https://howardwolinsky.substack.com/p/we-dont-need-to-rename-low-grade?s=r&fbclid=iwar1hqp8twtgjc9yuhghijetlp6lksmt1hlvvwq2x7rzlvn7-uf1knl3e8d0

TY Jim,
I do hover over all the prostate cancer websites. The guys in these groups are my guidance to maintaining the thoughts shared by patients in the real world and bring those thoughts to the panels and groups I serve. To be clear, I am one step away from supporting the name change. But as most here note there is too large of an error rate on Dx and a decision to rename could potentially mislead a guy to not give their diagnosis the attention it will require through the coming years.

The JCO paper was written by a couple colleagues I have worked with through the years. Scott, Matt, and Howard have sincere intentions. Howard is a 1 in 70 cores through multiple biopsies through the years AS patient and a well-known medical journalist. After 15 years he has prostate issues relating to repeat biopsies. He is a stakeholder for certain. Matt is up there with Klotz, Chodak, Carroll, and many others that bang the AS drum. Scott and I are published together on guidelines including one about to be released that is relevant and we are serving another panel. I have only met Vickers (MSKCC) once and I never met Berlin. I know these guys are largely pro-early detection, and while I disagree with renaming at this time, their intentions are genuine and realistic. I've held these debates on other panels. I have stood my ground based upon the need for better and more accurate diagnosis.

Howard admits that the group that was polled was largely long term AS guys. There were some physicians, and while favorable to renaming, it was not a consensus among them. But it was mostly in favor from those in practice. Howard and I agree that if you ask a prostate cancer survivor about it, that it matters if you are asking an AS patient versus a patient that was treated - you will get differing results. The stakeholders are many, but the stakeholding largely belongs to the G6 at presentation guys and the physicians attending them. And while they don't know it, future G6 men as well.

The purpose of the poll was set by Howard and the Active Surveillance Patients International and Answer Cancer. groups It was to first hold a webinar with AS guys and key physicians on renaming, and see what the response was. So yes it was biased in the patient pool. It started against and ended in favor.

Don't expect this debate to just go away. I think it will if we can get better diagnostic tools and reduce the hazard ratios, hopefully to nil or non-existent. Once we can safely reduce the incorrect detections while setting a solid plan for those with indolent confirmed disease, I'm for it. The psychosocial and psychological harms are real. Potential hope exists with liquid biopsy but in research I am working on, it's not likely current research can satisfy the argument.

Until there is the "right" answer, it's good, I think, that the debate continues.

Hey guys, I pray that all are fighting with spirit. I am one of those who fell through the cracks when my family physician (now former family physician) adopted the attitude that PSA screening was not a viable method to detect Pc if there were no obvious lesions felt during a DRE. My PSA OF 35 was a surprise to him and I still want to kick his ***. My Gleason 8 biopsy (6 out of 12 cores positive) sent me on a road of panic. A second opinion from Epstein & Co. revised me to a GS of 6 in all cores. His explanation was that mucinous fibroplasia clouded the original diagnosis. BUT I still have a pretreatment PS A OF 35 which is coming from somewhere according to my urologist.
Radiation and ADT Has been my life style for the last 2 years. P SA has been undetectable for 18 months and I will be waiting to see what my body will do for the net 5 years.
My point is that I don't think I would have gone with the AS strategy and risk evolving out of the nonmetastatic category

Diagnosed 7/14/2020
6 out of 12 cores positive GS 8. Revised to GS 6
5 1/2 weeks of hypofractionated RT and about to complete 24 months of lupron injections
Current PSA <.01