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Myth: "Gleason 6 never progresses"

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Posted 11/19/2017 9:55 PM (GMT 0)

Pratoman said...
And a third...no guarantees whether a G6 chooses AS or treatment,

A good question to ask oneself... would I rather treat now, while there is reason to believe that I'm a G6, or would I rather do AS and take the risk that by the time it becomes evident that I need treatment, I'm a g7(4+3).

Just to stir the pot ;-)...but IMO, a valid question, nevertheless.

Hi Ken, I'll bite on this challenge. Since 55 percent of the Klotz AS patients were still doing it after 20 years, that means you have a decent chance of avoiding treatment for many years. I'm betting that both surgery and radiation will be replaced by immunotherapy at some future point. If the bet goes wrong, and the clock wins on needing treatment, the stats from JH shown no additional risk of mortality from the time spent on AS.
Posted 11/19/2017 10:00 PM (GMT 0)
This is a good article and a good discussion. Important to keep in mind (and TA's article suggests this) is the difference between a GS6 biopsy result and a GS6 pathology from examining the entire prostate. I've got a GS6 diagnosis, but that's based on a single biopsy so there's a fair chance that something more serious was missed. Even with a follow-up biopsy (like the one I had this past Friday) there's still some chance of more serious cancer being missed. This uncertainty is just the nature of the beast.

To add to the uncertainty on the issue, I note that the Gleason score standards were updated in 2005, such that poorly formed glands and some cribriform glands that were considered as Gleason pattern 3 in the original system were upgraded to Gleason pattern 4 in the modified system. Since such cribriform glands have been shown to lead to adverse prognosis, this complicates the endeavor to link diagnoses today with long-term studies of GS6 patients.
Posted 11/19/2017 10:10 PM (GMT 0)

ASAdvocate said...

Pratoman said...
And a third...no guarantees whether a G6 chooses AS or treatment,

A good question to ask oneself... would I rather treat now, while there is reason to believe that I'm a G6, or would I rather do AS and take the risk that by the time it becomes evident that I need treatment, I'm a g7(4+3).

Just to stir the pot ;-)...but IMO, a valid question, nevertheless.

Hi Ken, I'll bite on this challenge. Since 55 percent of the Klotz AS patients were still doing it after 20 years, that means you have a decent chance of avoiding treatment for many years. I'm betting that both surgery and radiation will be replaced by immunotherapy at some future point. If the bet goes wrong, and the clock wins on needing treatment, the stats from JH shown no additional risk of mortality from the time spent on AS.

Yup, I get that. And to be clear, in no way, am I suggesting that AS is a bad idea. Wouldn't do that. I guess what I'm suggesting is thatbits a great idea for some, and not so much for others.
There is no easy black and white answer. We just need to be aware of the possibilities.
Posted 11/19/2017 10:17 PM (GMT 0)
A good question to ask one’s self when newly diagnosed with low risk PC is whether I should opt for an unnecessary aggressive treatment while all hopped-up with the emotional charge of so-called “cancer,” or wait without consequence to see if treatment might or might not be needed down the road.
Posted 11/19/2017 10:29 PM (GMT 0)
Slanted question
Posted 11/19/2017 10:53 PM (GMT 0)

Pratoman said...
And a third...no guarantees whether a G6 chooses AS or treatment,

I disagree. There are guarantees. if I remember correctly, in Klotz's AS study, out of thousands of patients, only 3 were found to have metastasized, and those were found to be high risk at the confirmatory biopsy.

Pratoman said...
A good question to ask oneself... would I rather treat now, while there is reason to believe that I'm a G6, or would I rather do AS and take the risk that by the time it becomes evident that I need treatment, I'm a g7(4+3).

But a GS 4+3 discovered on AS is different from a GS 4+3 discovered on a first biopsy. The difference is that the AS patient has been watched closely over time. It is known that his cancer has not metastasized and is 100% curable (by klotz's statistics)
Posted 11/19/2017 10:58 PM (GMT 0)

Tall Allen said...

Pratoman said...
And a third...no guarantees whether a G6 chooses AS or treatment,

I disagree. There are guarantees. if I remember correctly, in Klotz's AS study, out of thousands of patients, only 3 were found to have metastasized, and those were found to be high risk at the confirmatory biopsy.

Right, so no guarantees, because you may not have been G6 in the first place.

Pratoman said...
A good question to ask oneself... would I rather treat now, while there is reason to believe that I'm a G6, or would I rather do AS and take the risk that by the time it becomes evident that I need treatment, I'm a g7(4+3).

[quote] But a GS 4+3 discovered on AS is different from a GS 4+3 discovered on a first biopsy. The difference is that the AS patient has been watched closely over time. It is known that his cancer has not metastasized and is 100% curable (by klotz's statistics)

I don't know, how does one know they weren't a g7 all along if they were on AS? I was watched very closely before I was even diagnosed, with 3 month PSA' S regularly after my first negative biopsy. The g7 was likely there all along, and missed. Had I been on AS, with the g7 at the apex, I might have had a problem. (Might still)
There's no question in my mid that once you are diagnosed, G6 or whatever, you are taking a risk choosing AS, and you are taking a risk having treatment that might not be necessary. But you'll never know. So pick your poison. No free lunch. That was the point of my post.

Post Edited (Pratoman) : 11/19/2017 4:01:49 PM (GMT-7)

Posted 11/19/2017 11:00 PM (GMT 0)

Froggy88 said...
To add to the uncertainty on the issue, I note that the Gleason score standards were updated in 2005, such that poorly formed glands and some cribriform glands that were considered as Gleason pattern 3 in the original system were upgraded to Gleason pattern 4 in the modified system. Since such cribriform glands have been shown to lead to adverse prognosis, this complicates the endeavor to link diagnoses today with long-term studies of GS6 patients.

Good point. But the effect of that change was to make both a diagnosis of GS6 and GS7 less risky now than in the previous studies, by the Will Rogers Effect. So prognosis for both will be better.
Posted 11/19/2017 11:26 PM (GMT 0)

Pratoman said...
Right, so no guarantees, because you may not have been G6 in the first place.

The confirmatory biopsy is critical. Leonard Marks (my Uro who is in charge of the UCLA AS program) does not consider a man to be on AS until after the confirmatory biopsy (mpMRI-targeted) within a year. I think that's a good practice.

Pratoman said...
I don't know, how does one know they weren't a g7 all along if they were on AS? I was watched very closely before I was even diagnosed, with 3 month PSA' S regularly after my first negative biopsy. The g7 was likely there all along, and missed. Had I been on AS, with the g7 at the apex, I might have had a problem. (Might still)
There's no question in my mind that once you are diagnosed, G6 or whatever, you are taking a risk choosing AS, and you are taking a risk having treatment that might not be necessary. But you'll never know. So pick your poison. No free lunch. That was the point of my post.

You were not on anything close to AS. The essential part of AS is biopsies.You can even do without PSAs and DREs, as long as you have periodic biopsies. That is how you know what your true Gleason score is - the more biopsies (especially targeted or saturation biopsies), the more your assurance.

At Johns Hopkins, the 15-year cancer-specific survival and metastasis-free survival were 99.9% and 99.4%, respectively on 1298 men. If that's not a guarantee, what is? What is the risk?
Posted 11/20/2017 12:15 AM (GMT 0)
I disagree. There are guarantees. if I remember correctly, in Klotz's AS study, out of thousands of patients, only 3 were found to have metastasized, and those were found to be high risk at the confirmatory biopsy.....

Those 3 were high risk and didn't know it, so being on AS, they metastasized. Maybe they would hve even if they were treated immediately. Maybe they didn't. Unknowable. Those 3 men took a risk. And lost. Sure, only 3 men out of thousands. Statistically insignificant. Tell them that.
Posted 11/20/2017 1:09 AM (GMT 0)
I hear what you say tall Allen, if you do AS right and get the multiple biopsies and imaging studies you have a 99% chance of catching any Gleason 6 progression. You do a great service educating newbies of knowing what they’re doing ahead of time.
And I hear you pratoman, what if you’re the unlucky 1%? It depends on what kind of a gambler you are. I went for the trifecta with surgery- no cancer, no incontinence, no ED. It was long odds and I lost. Still using trimix for ED. Life is full of gray areas....
Posted 11/20/2017 1:31 AM (GMT 0)
Agree with everything you said mspt. And grey areas indeed, especially when it comes to this disease.
Posted 11/20/2017 1:50 AM (GMT 0)

Pratoman said...
I disagree. There are guarantees. if I remember correctly, in Klotz's AS study, out of thousands of patients, only 3 were found to have metastasized, and those were found to be high risk at the confirmatory biopsy.....

Those 3 were high risk and didn't know it, so being on AS, they metastasized. Maybe they would have even if they were treated immediately. Maybe they didn't. Unknowable. Those 3 men took a risk. And lost. Sure, only 3 men out of thousands. Statistically insignificant. Tell them that.

Whoa, whoa here. So, should thousands of men "not take a risk" and possibly suffer with lifelong quality-of-life issues in order to be more "safe"?

Sorry, (and, no offense) but I'll gladly take those odds in order to continue living a normal life.
Posted 11/20/2017 1:54 AM (GMT 0)
Not saying that at all. I've been saying all along in this thread that I'm not saying AS is a bad idea. I'm only saying it's a personal decision. And in making that decision, men should be informed that AS , while it has very high odds of defining a time for treatment without detrimental effect, is not guaranteed to do so.

Don't misinterpret.

....Sorry, (and, no offense) but I'll gladly take those odds in order to continue living a normal life.....
And that's a perfectly reasonable decision. As long as you are informed of the risk, no matter how slight.
Posted 11/20/2017 2:02 AM (GMT 0)
Thanks, Pratoman. We're good.
Posted 11/20/2017 2:44 AM (GMT 0)
Pratoman, I recognize that a mortality risk of 99.9% is not the same as 100%, but seriously? I think that is as close to a guarantee as there ever can be, and by following up with mpMRI-targeted biopsies, it would be 100%. You are right that it is tragic for the 2 men out of 1298 who died of prostate cancer. Let's agree then that this is not an almost perfectly safe protocol to follow.

Compare that 0.1% chance of dying with a lifetime risk of of 0.9% of dying in a motor vehicle accident or a 1.0% risk of dying from accidental poisoning/toxic reaction.
Posted 11/20/2017 4:31 AM (GMT 0)
This is from the abstract...

Conclusion
Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.

So in a cohort of 994 patients, about 27 developed mets and 15 died. Can we say what would have happened had they been treated up front? Dunno.

Also, klotz study was on AS at a single academic hospital center. I wonder what the numbers would be in a multi institutional center which included regional, local hospitals and urologists where so many men get followed, and where standards may not be as strict.

Can't stress enough, I'm not saying AS is bad, just saying IMO the risk may be understated by some of these studies, and men should be made aware of them, without scaring them off the idea.
Posted 11/20/2017 5:08 AM (GMT 0)
Never say never.

I'm a G6 that went to G8 in a seemingly short time frame...

I'm now of the opinion that if a person is physically able to handle the surgery and recovery, I'd get it out of me sooner rather than later.
Posted 11/20/2017 1:18 PM (GMT 0)
This thread’s discussion on PCa progression from G6 to G7 caused me to think about PCa regression (like in breast cancer).

There seemed to be less cancer in my surgically removed prostate then was indicated in my biopsy. Does anyone know if there have been studies done on PCa regression?
Posted 11/20/2017 1:35 PM (GMT 0)
Dr. Epstein has written that about 16 percent of cases that were biopsied as Gleason 7 turned out to be Gleason 6 after RP.

I have heard of a few cases where the post-RP pathology was negative. I guess those would be the ultimate examples of over-treatment.
Posted 11/20/2017 6:05 PM (GMT 0)
Pratoman-

Like all therapies, active surveillance protocols have improved over time. Klotz's was the first in North America, and was started well before mpMRI/US fusion. There were some differences in Klotz and Johns Hopkins protocols - particularly the use of more stringent Epstein criteria, annual biopsies, and stricter criteria for treatment. Unlike Johns Hopkins, Klotz's numbers also included some favorable intermediate risk patients. I'm not saying Klotz's protocol is bad; in fact, I think it is good. But if you want a risk-free program, and I think 99.4% freedom from metastasis is risk free, you'd have to look at the Johns Hopkins protocol.
Posted 11/20/2017 6:53 PM (GMT 0)
As usual, I enjoyed reading another article from Tall Allen because it was very clear and answered some crucial questions with the info currently on hand.

As someone who was just diagnosed in August 2017 as a G6 after his fifth biopsy since 2009, it took me a bit to get my head around Active Surveillance (AS) as "treatment" rather than just "sitting on my hands... and waiting."

My confirmatory biopsy will happen sometime between March and May 2018. I'm taking AS in six-month time frames. I know it could be all over as quickly as it started once a higher Gleason score is found.

My main goal is to play the odds and hedge my bets as best as possible -- balancing a side effect-free life for as long as possible, and hit the surgery and/or radiation "red button" at the correct and precise moment. I know I might be pressing that button in 7 months, 24 months, or 60 months. My concerns about "undertreating" now are just as high as "overtreating" now.

I look at it this way -- If I have to consider immediate treatment in 2022 instead of 2017, that means a wealth of more research, results of countless new studies, perhaps different treatment options, and hundreds of new and very informative Tall Allen articles to consider!
Posted 11/21/2017 1:49 AM (GMT 0)

Tall Allen said...
Pratoman-

Like all therapies, active surveillance protocols have improved over time. Klotz's was the first in North America, and was started well before mpMRI/US fusion. There were some differences in Klotz and Johns Hopkins protocols - particularly the use of more stringent Epstein criteria, annual biopsies, and stricter criteria for treatment. Unlike Johns Hopkins, Klotz's numbers also included some favorable intermediate risk patients. I'm not saying Klotz's protocol is bad; in fact, I think it is good. But if you want a risk-free program, and I think 99.4% freedom from metastasis is risk free, you'd have to look at the Johns Hopkins protocol.

Point well taken, Allen.
Posted 11/21/2017 5:07 AM (GMT 0)
Prato,
Death on the operating table during surgery carries more risk than dying while on AS. You are trading the risk of immediate death for the risk of death in the future. The risk is small in either case.
Posted 11/21/2017 5:12 AM (GMT 0)

ASAdvocate said...
I'm betting that both surgery and radiation will be replaced by immunotherapy at some future point. If the bet goes wrong, and the clock wins on needing treatment, the stats from JH shown no additional risk of mortality from the time spent on AS.

I have a hunch that you're right about the future of PCa treatments.
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