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Posted 4/26/2017 5:12 PM (GMT 0)
If one is found to have Gleason 6 cancer, is he statistically more likely to have or ultimately develop clinically significant cancer, G7 or higher, than someone that does not have any G6?

I believe I have read the G6's do not develop into higher grades - whatever is born as a G6, stays as a G6, and as we know, there are many men with G6. What I don't know, but feel like I should, is whether studies have been done that show men with G6 or more likely to develop G7 or higher eventually.....or not.
Posted 4/26/2017 5:19 PM (GMT 0)
According to a JH study (https://www.ncbi.nlm.nih.gov/pubmed/24123208), between 12 and 24% will progress to G7 or higher, but it's not clear if that's because the original diagnosis was wrong (missed the G7 on initial biopsy or just mis-interpreted it), or if there's a real progression in the lesion.
Posted 4/26/2017 5:24 PM (GMT 0)

searchinginla said...
...but it's not clear if that's because the original diagnosis was wrong (missed the G7 on initial biopsy or just mis-interpreted it), or if there's a real progression in the lesion.


A single biopsy may (and does occasionally) miss an existing higher grade PC (which is why AS programs always include a second, confirmatory biopsy for the already-assessed favorable-risk cases, which nearly eliminates the probability of "missing" more existing cancer)...but the notion of "progression" is often misunderstood.

The current understanding is that existing lower-grade prostate cancer cells do not, themselves, "morph" into a higher grade. Rather, new higher grade cells of PC may develop in the future. The cells are basically understood to exist as the grade the are "born as." The term "progression," as in case progression, is used whenever higher grade Gleason cells are found. RickTrin, this is what you were talking about...

Hope this helps clarify...
Posted 4/26/2017 5:38 PM (GMT 0)
You need TA for this one.

I think the studies tend to support that G6 doesn't progress.

Andrew
Posted 4/26/2017 5:45 PM (GMT 0)
biopsy results never completely eliminate the possibility of higher grade cancers. that is why on AS they monitor PSA and repeat biopsies.
Posted 4/26/2017 5:49 PM (GMT 0)
Thanks for responses which are helpful.

Intuitively, it would seem that if someone has a G6 he would be more likely to develop G7 (not progression from G6, but as a new and separate cancer) than someone with no G6. The G6 person just being more "prone" to prostate cancer of any form. That said, given that so many men have G6, many never knowing that because there was no reason to test for it (PSA never elevated), I didn't know if it had ever been proven that the G6 population is statistically more likely to have G7 than that without G6.
Posted 4/26/2017 5:53 PM (GMT 0)
G6 can progress, but it takes a long time - often more than 10 years. We know this from long running active surveillance trials like Toronto's where there is over 20 years of f/u. about half of the low risk patients progressed to higher grade in that time, about half did not (a plateau was reached at 15 years). They did a lot of biopsies on those men, so it wasn't just that they missed it. This is why active surveillance is a lifelong commitment.

No one yet knows how to identify the G6s that will progress from the ones that won't.
Posted 4/26/2017 5:59 PM (GMT 0)
TA, I just watched a video by Dr. Klotz, who runs that AS program in Toronto. He said that he is not convinced that a G6 has ever been proven to morph into a higher grade. So, maybe "progress" is not the right term here. We do all seem to be saying that someone with G6 can certainly develop other cancer cells that are higher grade.
Posted 4/26/2017 7:52 PM (GMT 0)
I go by the "common sense" template...it makes sense that it does progress into a more aggresive dis ease over time...I mean its cancer...thats what cancer does...only it does it more slow...during the time of that happening ...it also mmakes sense..to me...that higher scores develop independantly...pca is a highly personalized disease...but their are commonalities to anything...in some fashion...main point...no one really knows...do they...thats the takeway from all studies...if they did know...there would be no need to have any more studies on it...simplistic...yet factual and true... ps I also believe that a individual does have some control of his cancer...by what that individual does or does not do over a period of time...that just makes sense to me also...do I understand it...no but it "just makes sense "
Posted 4/26/2017 8:46 PM (GMT 0)
Here is a speculative theory: cancer begin with a random genetic mutation. When cells have become cancerous they also become more likely to further mutate because of failure of the DNA repair system. As G7 is more poorly differentiated (more mutated) than G6 (less mutated) it could be that some G6 cells mutate to G7. Also the random genetic mutation can immediately create brand new G7. The random genetic mutation goes on in continuously in our bodies and the DNA repair system becomes less effective with increasing age, thats why PCa is the old mens disease.
Posted 4/26/2017 9:44 PM (GMT 0)
The breakdown of DNA repair is certainly part of it. One lab study found that both G6s and G8s arose from the same progenitor cell. There are also tissue-related effects, and vesicles from cancer cells that turn healthy cells cancerous. I think we can safely say that men detected with GS6 only, even after repeated targeted biopsies, are not completely safe from higher grade disease.
Posted 4/27/2017 9:45 PM (GMT 0)
Good information by all. Take away has to be that someone with G6 is more likely to end up with G7 or higher, than someone with no G6. Seems obvious but didn't know if had been studied.

Another question if anyone cares to comment -- in AS criteria, PSA density below .15 is often included but if one had very minimal G6 found on biopsies, PSA less than 10 but due to prostatitis, PSA density > .15 would it be correct that he can't go onto a AS program.......and otherwise gets more significant treatment if the problem was prostatitis?
Posted 4/27/2017 10:46 PM (GMT 0)
Prostatitis should not exclude anyone from AS. But diagnosing it can be challenging. I don't know how much the Epstein criteria are still used - it depends on the AS program.
Posted 4/27/2017 11:23 PM (GMT 0)
Yes postatitis can be hard to detect and that would seem to be a good reason not to let someone with low volume G6 only but high PSA density be excluded from AS. I'm on AS and to date have only very low volume G6. Its a personal decision for everyone of course, but my attitude is that I'm not coming off AS based on PSA stats alone no matter what they are
Posted 5/8/2017 11:00 PM (GMT 0)
If a pre surgery mpMRI notes no sign of EPE, how reliable is that as to whether or not cancer has left the prostate?
Posted 5/9/2017 2:09 AM (GMT 0)
Not very. Staging with mpMRI is controversial. Sensitivity for staging is only about 50% - no better than a coin toss - a high rate of false negatives. However, if it does show ECE, it is probably correct (low rate of false positives).
Posted 5/9/2017 3:14 AM (GMT 0)
Wouldn't prostatitis make your PSA density go down instead of up? (larger prostate -> lower density with the same PSA value)
Posted 5/9/2017 3:47 AM (GMT 0)
Prostatitis does not enlarge the prostate significantly, but it can make PSA shoot up quickly and drastically. BPH enlarges the prostate with a slow steady increase in PSA.
Posted 5/9/2017 9:42 AM (GMT 0)
Ok so although the negative predictive value of a mpMRI (>90% from what I've been able to find) for clinically significant cancer within the prostate is high, it doesn't help much as to whether cancer has left it. Although presumably if no cancer shows up in the prostate on an mpMRI, it's likely none has escaped?
Posted 5/9/2017 3:31 PM (GMT 0)
RickTrin- Its NPV for any cancer within the prostate is low- what you are looking at is its NPV for significant (large/high grade) cancer. One can have a EPE even with a GS6.
Posted 5/9/2017 4:44 PM (GMT 0)
Ok got it. Thanks. And probably another dumb question but even a G6 outside the prostate can cause trouble, correct?
Posted 5/9/2017 5:21 PM (GMT 0)
Well, it depends on what you mean by "trouble." GS6 can eat into healthy tissue. Over time, about half of men diagnosed, even with numerous biopsies, as GS6 have been found to have higher grade cancer - So it seems that, at least in some men, there is true grade progression and not just undetected higher grades. The mechanism for that remains unclear - it may be from progenitor cells or from a slow process of genetic breakdown or both. However, while the tumor is GS6 only (assuming it truly is), it is incapable of metastasizing.
Posted 5/15/2017 12:05 AM (GMT 0)
I can only give you my own history. I had a G6, and thought; Whew, they caught it early, it is a low grade, therefore it should be cured when I get my prostate removed.

As you can see from my history, it was not the Gleason score that mattered, as much as where the cancer was in the prostate.

My advice would be to not take a chance on if it gets to a higher G score to take action.

If the apex (exterior edge) is involved, it may escape the prostate and become advanced PC even with a low grade, and you get the prostate removed. You would not know until you have the prostate removed as to where the cancer is or how much is involved. The biopsy is a sample of only a small portion of the prostate.
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