Rethinking risk stratification - Prostate Cancer N...

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Rethinking risk stratification

Tall_Allen profile image
39 Replies

Most of us here are familiar with the NCCN risk stratification system for localized prostate cancer: Low, Intermediate, and High Risk with two subcategories in each of those. Some researchers have proposed a new system called STAR CAP. I think what we need instead is a multi-institutional registry with easy-to-use nomograms. Here's a discussion of the issues:

prostatecancer.news/2021/08...

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Tall_Allen profile image
Tall_Allen
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39 Replies
Ahk1 profile image
Ahk1

You continue to amaze me, TA. You spend all this time studying, analyzing, researching and writing these very informative documents even though you were cured. Very admirable. Thanks a lot. We on the site appreciate your great efforts.

cesanon profile image
cesanon in reply to Ahk1

No one is ever certain they are cured.

And most of us die from other causes.

Tall_Allen profile image
Tall_Allen in reply to cesanon

I am!

cesanon profile image
cesanon in reply to Tall_Allen

How do you know that you are cured?

What is the criteria?

Tall_Allen profile image
Tall_Allen in reply to cesanon

My criterion is a stable low PSA (I had SBRT).

cesanon profile image
cesanon in reply to Tall_Allen

You normally hew quite close to peer-reviewed published studies.

Is this your subjective assessment. Or is it based on one or more studies?

If so, for how long must the PAS be stable and within what range to be considered low?

Thanks

Tall_Allen profile image
Tall_Allen in reply to cesanon

"Cure" is always a subjective assessment. All one can say objectively is there is no evidence of disease. It's like my subjective assessment that I won't be run down crossing the street. It's a good enough bet that I do it all the time. Of course, I look both ways just like I get annual PSA tests.

With RT, after PSA goes below 0.5 and stays there, it is prognostic that one will die of something else.

cesanon profile image
cesanon in reply to Tall_Allen

Well can I ask you how many years of stable PSA it took you to come to your personal conclusion that you were likely cured.

The reason I ask is that you are about as well informed about the subject as anyone so that your intuition on the subject has to be a well-informed intuition.

So how many years of stable PSA did it take to come to this tentative/provisional personal assessment?

Tall_Allen profile image
Tall_Allen in reply to cesanon

My PSA went below 0.5 after 4 years of bouncing around. I think it was at that point I truly relaxed about it. Maybe a little too relaxed- I neglected to get a PSA one year. It's been at 0.1 or <0.1 for the last 5 years.

addicted2cycling profile image
addicted2cycling in reply to Tall_Allen

Tall_Allen wrote --- " ...I had SBRT for low-risk/high-volume prostate cancer in 2010. Cured. No residual side effects... "

Just curious as to what your "low risk" was??? If you care to share.

TIA

Tall_Allen profile image
Tall_Allen in reply to addicted2cycling

all GS6

4tran4 profile image
4tran4 in reply to Tall_Allen

TA, How long is “stable low”? Thank you for keeping us informed!

Tall_Allen profile image
Tall_Allen in reply to 4tran4

Last 5-6 years

Schwah profile image
Schwah in reply to Tall_Allen

Do people like you never relapse years later from a stray dormant cell?

Schwah

Tall_Allen profile image
Tall_Allen in reply to Schwah

I do not intend to! True GS6 is incapable of metastasis.

maley2711 profile image
maley2711 in reply to Ahk1

Here is the STAR- CAP nomogram......

umich-biostatistics.shinyap...

Here is info on another nomogram now apparently used by NHS physicians........

cambridgeprostatecancer.com...

prostate.predict.nhs.uk/

A nomogram will never give a patient any absolute certainty of what his result will be, of course......no matter how many variables are used. More refined tools will hopefully let us do a better job of reducing both overtreatment and undertreatment. Hopefully men 10-20 years from now will be able to benefit!

A variable that will probably never be incorporated is the quality of the patient's care team!!

Tall_Allen profile image
Tall_Allen in reply to maley2711

The link to the STAR CAP nomogram is in the article. Thanks for the NHS nomogram. I like the functional outcomes. I don't like that it predicts mortality rather than recurrence.

maley2711 profile image
maley2711 in reply to Tall_Allen

There is disagreement about the most important endpoint...... for various reasons. One I recall is the possible difference in definitions of other endpoints. I'd like to see relative survival/mortality...relative to expected survival for someone who does not have PCa at that age, but otherwise same medical condition. Another huge project...but doable if there were the will?

Tall_Allen profile image
Tall_Allen in reply to maley2711

If you read my article, I argue that survival is NOT at all an important endpoint for men with localized PC with more than 10 years of actuarial survival left.. There is a link to survival estimate based on actuarial survival and comorbidities.

maley2711 profile image
maley2711 in reply to Tall_Allen

I know that is your viewpoint, and MANY agree, and I look at all endpoints.....I beliee ProtectT used survival? and also noted other endpoints. Survival perhaps more important for G > 3+4. PSA failure certainly for hope of avoiding dreaded ADT!!i simply pointed out that there are other viewpoints on the best one endpoint...eg., my Uro seems to like survival.

Yes, there is the MSK life expectancy nomogram, and I suppose a number of others, but it would be nice to have the data incorporated into one nomogram....that's all.

Tall_Allen profile image
Tall_Allen in reply to maley2711

My concern is for the decision the localized PC patient is faced with. Survival 10 years away, after whatever therapy, really does NOT help the patient make the decison over which therapy to choose NOW. If there is a way to use overall survival to help make a treatment decision for localized PC, please explain just how that would work.

As for ProtecT - using a 10-year mortality endpoint was certainly a design flaw. Fortunately, they included secondary surrogate endpoints like metastasis-free survival. They planned to detect mortality differences, but couldn't.

They thought there would be more deaths in the ten years of follow-up, but almost all the men defied those expectations. That's partly because of all the great new life-prolonging drugs that became available in the 21st century; drugs like docetaxel, Xtandi, Zytiga, and Xofigo. Also, in a clinical trial, patients are very closely diagnosed, treated, and monitored. They get far better care than the average patient in community practice. There were only 17 prostate-cancer related deaths

Men also survived longer because of progress in treating other diseases. But most of all, men lived longer because they frequently visited doctors as part of the study, during which they were closely monitored for other illnesses. There were only 152 deaths from all other causes, only 9% of the total sample size. Men were 50 to 69 years of age (62 years median) at the start of the study and were tracked for 10 years. On average, based on US actuarial tables, about 18% should have died from all causes. So the mortality rate was half of what was expected. On the average, men in the UK live two years longer than men in the US - not enough to account for the difference. Certainly, just being in a clinical trial watched closely by their doctors contributed to their longevity.

maley2711 profile image
maley2711 in reply to Tall_Allen

if there was a large dataset of men of approximately same age, health, and PCa clinical data, and the OS, and thus probably CSS,was significantly greater for one treatment than another(including all the salvage and palliative treatments done)...that would be meaningful, at least for some of us it would.

IMHO, almost any endpoint can be critiqued......no "right" one..but I may be wrong.

Tall_Allen profile image
Tall_Allen in reply to maley2711

Randomized clinical trials can certainly match patient characteristics, disease characteristics, and the initial treatment given to men with localized PC. Those trials last for up to 10-12 years at most. In that time frame, almost all will survive their cancer and a few will die from entirely irrelevant reasons. There is no way to continue following them for, say, 20-30 years and at the same time match them for all other salvage and palliative treatments.

Endpoints are chosen to be meaningful and practical.

maley2711 profile image
maley2711 in reply to Tall_Allen

As usual, you are correct.

maley2711 profile image
maley2711 in reply to Tall_Allen

TA -

you previously mentioned metastasi-free survival as a good indicator of treatment effectiveness, correct" ? With tat in mind, do you find anything meaningul from this study....

ncbi.nlm.nih.gov/pmc/articl...

Of course, larger study numbers would be needed to form a reasonable final conclusion...and a lnger study time of course.....maybe 8-10 years? Nevertheless, not discouraging re radiation option.

WilsonPickett profile image
WilsonPickett

Alan, I should be continually expressing my appreciation for all your postings and clear knowledge on the subject. For those of us getting ready to undertake either surgery or radiation, I can certainly say for myself that you’ve been a big help, just in the way you are able to help us make sense of a lousy situation. As always thank you.

cesanon profile image
cesanon

I never found the NCCN risk stratification system to be credible or useful. It just seemed too simple to me.

I read your article. I was unaware of the other systems.

To create such a system you need both a deep and a wide subject matter understanding.

My guess is that you spend more time reading a wider breadth of research than the vast majority of prostate cancer Docs.

Dr. Myers actually had a researcher on staff that did that for him. Probably the only doc around to do that.

If you want to create a new and widely accepted risk stratification system, I submit that you need to turn your current article into something a little more, recruit a credible MD to sign on as a coauthor, then publish it as a non-peer-reviewed preprint.

Then use that to recruit authors at whatever institutions that have the data you need.

Just saying

Tall_Allen profile image
Tall_Allen in reply to cesanon

I agree. And I already started the ball rolling. I have some big guns behind it, but I'm sure the STAR CAP researchers will take some convincing.

cesanon profile image
cesanon in reply to Tall_Allen

Do what you can and move ahead with what you have.

Even if you are unable to recruit the STAR CAP researchers at an early stage, Once you have recruited who you can, you should approach with an "Oh Great One" what are your recommendations for this provisional plan, Oh Great One. LOL

If they deign to step down and give you their critique, you are halfway to recruiting them to the team as the project matures.

You just need to approach them with some humility.

Tall_Allen profile image
Tall_Allen in reply to cesanon

I talk to doctors all the time and have never had a problem. But they've invested a LOT of work in STAR CAP. I think peer pressure is the only hope.

Cooolone profile image
Cooolone

Thank you for posting!!!

Of course now comes some time to read, absorb and follow the breadcrumbs!

:)

Fiddler2004 profile image
Fiddler2004

Thanks for this...

tallguy2 profile image
tallguy2

This is an outstanding summary of where medicine is today in looking at outcomes. Thanks for the compilation from numerous sources. Excellent!

Canuck2020 profile image
Canuck2020

I had prostate brachytherapy (PB) with J Crook in 2021. Like you my goal is to get to PSA <0.2 in the next 5 years and stay there. 98% disease free beyond 15 years is a great number. See attached slide.

Biochemical Definition of Cure for Brachytherapy Patients
Tall_Allen profile image
Tall_Allen in reply to Canuck2020

Thanks - love those stats!

SkyH profile image
SkyH in reply to Canuck2020

Just curious did you have hormone therapy as well?

Canuck2020 profile image
Canuck2020 in reply to SkyH

No I did not SkyH. My prostate was of normal size as well as my testosterone level. PSA was 7.2 before treatment and Gleason 3+4 with only 2 cores showing cancer. I was actually on AS because of Covid before my treatment in April, 2021. After 3 months of high dose brachytherapy it is now 0.49. The goal is < 0.2 within 5 years.

LeeLiam profile image
LeeLiam

I had seeds and EBRT in 2006. It took 5 years bouncing around to get to <0.2. The next year was 0.1. The next year <0.1. Then three more years at 0.1. So, 6 years <0.2. Then it started a steady increase. Last March PSA was 4.4. Never say never.

Tall_Allen profile image
Tall_Allen in reply to LeeLiam

I was low risk to begin with.

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