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2011 Study: Gleason Pattern 5 Is the Greatest Risk Factor for Clinical Failure...

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Posted 11/16/2018 3:04 PM (GMT 0)
I'm not sure if this has been posted before. (I kind of lose track of articles I may have posted, since I'm not organized enough to have them listed out in a blog somewhere.) It's from 2011 so getting a bit old, but the radiation doses were at least 75 Gy. That's low by today's standard, but not radically so.

Anyway, for the G9/10 Crew, this is just a reminder that the presence of the Gleason Pattern 5 cells is a significant risk factor. This kind of analysis/study affirms yet again that this variant of PCa requires throwing the kitchen sink at it.

It also supports one of my ongoing frustrations with our G9/10 being lumped in with G8 for risk classification in various studies. That blurs our results with cases having significantly better outcomes. So studies evaluating treatments and outcomes may miss something that could be effective for G9/10, because the G8 mixed in distorts the results. Practically speaking though, there generally just aren't enough G9/10 cases in any study cohort for them to draw statistical conclusions. If a scientist gets a grant for a study, they'd better darn well draw conclusions or their sponsor will be unhappy! So, they fiddle the numbers to get answers acceptable to whomever paid for the work.

Gleason Pattern 5 Is the Greatest Risk Factor for Clinical Failure and Death From Prostate Cancer After Dose-Escalated Radiation Therapy and Hormonal Ablation

From the abstract:
Conclusion
The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.
Posted 11/16/2018 3:26 PM (GMT 0)
Well, I’m a G8 (4+4). But my pathology showed focal areas of 5, so really, I’m a G9 from the viewpoint of many clinicians. And unfortunately, I’ve been having the poor outcome to bear that out. 😐
Posted 11/16/2018 3:40 PM (GMT 0)
This No. 5 your referring too, Is that the grade group.
Posted 11/16/2018 4:09 PM (GMT 0)
Mike, there is Gleason Grade and Gleason Score. The grades run 1 through 5, with 1 and 2 being non-cancerous, 3 being low risk and 4 and 5 being the high risk cancer that can cause a lot of damage and be more difficult to cure and control.. Then the Gleason Score is computed by adding two dominant Grades found in the core sample. Like 3+4 to get a Gleason Score of 7. In your case you are either a 4+5=9 or a 5+4=9. Either way it is clearly high risk and the presence of the 5 heightens the risk status.

Jerry's point deals with the presence of any Gleason Grade of 5 which brings significant risk for adverse experience and treatment difficulty. So a 4+4=8 would be slightly less risk than a 5+3=8 because of the presence of the G5.. So the Score alone is not always adequate to assess the risk as you must look at each grade and the amount of the grade present. Clearly a score of G9 or G10 are both in the highest risk strata, but so is a 5+3 or 3+5, both being G8, but very high risk due to the presence of G5.

In my case, my doctor said he treats to the highest Gleason Grade. So with me the G3 in many of the samples were not considered. He focused on the fact that I had G4 and a good amount of it. His experience is that too many doctors under-treat the higher risk situations. He also posited that if I had as much G4 as was in the biopsy that there would be significant probability that there could also be some G5.
Posted 11/16/2018 4:34 PM (GMT 0)
Yep, that was what I heard from my URO post Bx: "We really don't like to see any 5". No doubt. Next week is 5 years since my diagnosis. It was part of my thanksgiving celebration that year! ;) Still hanging in there keeping a close watch on it.
Posted 11/16/2018 4:49 PM (GMT 0)
Oh yes ….those wonderful # 5's. I have way too many of those.

Could someone explain this to me. I have read many studies and am not quite sure how to read the hazard ratio and what it means. I understand the abbreviations FFM....CSS....and OS . It's these numbers that get me
confused (p < 0.002; hazard ratio [HR] 3.4 [1.7–7.1])

.The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7–7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5).
Posted 11/16/2018 5:40 PM (GMT 0)

Artist Mark said...
Oh yes ….those wonderful # 5's. I have way too many of those.

Could someone explain this to me. I have read many studies and am not quite sure how to read the hazard ratio and what it means. I understand the abbreviations FFM....CSS....and OS . It's these numbers that get me
confused (p < 0.002; hazard ratio [HR] 3.4 [1.7–7.1])

.The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7–7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5).

The hazard ratio is just the ratio of two outcomes. It's a comparative thing. So, if treatment A has 5 out of 100 fail, that may be set to 1. Then, if treatment B has a 10 out of 100 fail, the Hazard Ratio is 2 (10/5). So, double the risk of whatever. Conversely, if you set B as the 1.0 baseline, then treatment A has an HR of 0.5 (5/10). It's to clarify the relative risk of a group of things. In that study, they're giving a range of hazard ratios for some of those things.

This is terribly abused in media reporting. They say things like, "Doing Thing X doubles the risk of Bad Thing Y! Never do Thing X!! Film at 11". You've heard that countless times. What they don't say is the baseline risk may be 1 out of a billion. And yes, 2 out of a billion is an HR of 2, and is in fact double the risk. But come on, it's only 2 out of a billion! Statistics are so ripe for misuse, either intentionally or inadvertently.

The p value is sort of how "good" the conclusion is. Very small p values indicate strong statistical support. It's too deep to go much further than that here, and you can find out more with some web searches. It gets fairly obscure quickly.
Posted 11/16/2018 5:55 PM (GMT 0)
The p value is kind of a measure of the likelihood that the results are valid. The acceptable threshold is set at p=0.05 which means there is only a 1 in 20 chance that results are invalid. The lower the p value, the better.

At least this is what I recall from my college statistics course. It wouldn’t hurt my feelings to be corrected.🙂
Posted 11/16/2018 6:35 PM (GMT 0)
JNF..
Thank you for clearing that up....
Posted 11/16/2018 7:22 PM (GMT 0)
Jerry...
Thank you for clearing that up...I think...maybe.....alright.....I got it...sort of...yes ...no...of course....probably...sounds good...… I'll take your word for it. HaHa

I'm good at many things but.... numbers? Not so good.

So.... with the presence of GP5 it's 3.4 times more likely to have FFM than with GP8 (without GP5)? and so on?
Posted 11/16/2018 8:47 PM (GMT 0)

Artist Mark said...
Jerry...
...
So.... with the presence of GP5 it's 3.4 times more likely to have FFM than with GP8 (without GP5)? and so on?


It's stated kind of indirectly. More directly stated, G8 is 3.4 times more likely to have Freedom From Metastases (FFM) than G9. FFM is a good thing (Freedom From Metastases), CSS is a good thing (Cancer Specific Survival), and OS is a good thing (Overall Survival). You want more of all of them, higher is better. So G8 is 3.4 times better FFM, 12.9 times better CSS, and 3.6 times better OS. It bothers me a little, because those numbers are far higher than I would expect. So it makes me wonder a little about the study.

The point is really just that the presence of these Gleason Pattern 5 cells is clearly a significant risk factor. But we knew that anyway, didn't we?

These things are always tricky, and we're only looking at the abstract. Seeing the full article would aid understanding, but access to those is usually around $40 per paper. Maybe a medical library could obtain it; U of M's patient library has gotten papers like that for me in the past.
Posted 11/16/2018 9:43 PM (GMT 0)

Redwing57 said...
It also supports one of my ongoing frustrations with our G9/10 being lumped in with G8 for risk classification in various studies. That blurs our results with cases having significantly better outcomes.

Redwing - This study Surgery vs Radiotherapy in the Management of Biopsy Gleason Score 9-10 Prostate Cancer and the Risk of Mortality is not "lumped" with G8!

Interestingly, the study concludes that both maxRT and maxRP treatment options have equivalent risk of mortality for men with GS 9-10 biopsies. Pretty contradicting a fairly common view here at HW that RT would have better results than RP for high risk patients. These results might be something to consider for G9-10 men when deciding between surgery and radiation?

maxRT = EBRT + brachytherapy + ADT

maxRP = RP + adjuvant EBRT + ADT
Posted 11/16/2018 10:00 PM (GMT 0)
Jerry,
This post has been very helpful to me as I've wondered about these things for a long time and didn't know how to ask the question. This is why I follow you. Hey....I'm an artist...what can I say. I can count on you for all knowledge about #'s and graphs and PSA trends and such. smile
Posted 11/16/2018 10:56 PM (GMT 0)

Artist Mark said...
Oh yes ….those wonderful # 5's. I have way too many of those.

Could someone explain this to me. I have read many studies and am not quite sure how to read the hazard ratio and what it means. I understand the abbreviations FFM....CSS....and OS . It's these numbers that get me
confused (p < 0.002; hazard ratio [HR] 3.4 [1.7–7.1])

.The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7–7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5).

.........................................................................................................................................................................................................................................................................................................................................................................

Wow! That is impressive! With CSS being 13 times worse and FFM 3.4 times worse comparing a G9 - NOT to a 6 or even a 7, but to a high risk 8 - it makes me wonder how I am even still here. Particularly with me being a- so far after 5 years - a surgery only. I mean, G7's do MET and even die of PC, don't they? And I assume G8 is significantly worse than G7, and however much worse that is I am 13 times higher risk than G8? WOWZA!
Posted 11/17/2018 2:49 AM (GMT 0)
I went with what I believed was the best treatment for me, but once I made my choice, I'm done with the studies. The way I look at it, it's a binary value for all of us. Either we stay metastatic free or not. Same with CSS. Same with OS.

I'm just taking it a day at a time, thankful for the life I've lived, excited about living the days and years ahead with my wife and loved ones.
Posted 11/17/2018 1:22 PM (GMT 0)
Well, just because they didn't find any G5 cancer cells in the biopsy does not mean there weren't any there to be found, just that those particular samples didn't show any.

G4 cancer cells are on their way to becoming G5 cancer cells. The G5's are like amoebas, can move around and can turn noncancerous cells into cancer cells by injecting RNA into them to alter their DNA. It does not take many of those to cause problems.

Got a few of those, even after the trifecta..... sad
Posted 11/17/2018 3:47 PM (GMT 0)

Gemlin said...
...
Interestingly, the study concludes that both maxRT and maxRP treatment options have equivalent risk of mortality for men with GS 9-10 biopsies. Pretty contradicting a fairly common view here at HW that RT would have better results than RP for high risk patients. These results might be something to consider for G9-10 men when deciding between surgery and radiation?

maxRT = EBRT + brachytherapy + ADT

maxRP = RP + adjuvant EBRT + ADT

It's surely possible. Hypothetically, to the point of segregating G8 from G9/10, there could be a significant difference between those two for G8, but not G9/10. The "common wisdom" that RT is better for "high risk" G8-10 could potentially be misleading, if the G9/10 cases aren't actually helped as much by it. But, maybe no one realizes that due to the confounding. I think it's a long-term issue with many studies.

Given what this study says, I suppose then a person needs to consider which approach's constellation of side effects could be easier to live with. Long term risks of incontinence and ED, for example. Given similar outcomes, and that both involve ADT (yuck), the side effect choice kind of comes down to the usual radiation vs surgery decision.
Posted 11/17/2018 4:17 PM (GMT 0)

CAdogsRus said...
I went with what I believed was the best treatment for me, but once I made my choice, I'm done with the studies. The way I look at it, it's a binary value for all of us. Either we stay metastatic free or not. Same with CSS. Same with OS.

I'm just taking it a day at a time, thankful for the life I've lived, excited about living the days and years ahead with my wife and loved ones.

Excellent outlook, CA, and one that IMHO would allow lots of folks who seemingly read incessantly much less obsessive PCa depression.

Best of luck to you!
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