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Muscle Loss During Androgen Deprivation Therapy Is Associated With Higher Risk of Non-Cancer Mortality in High-Risk Prostate Cancer

pjoshea13 profile image
15 Replies

New study below [1].

Bottom line:

"each 1% decrease in {skeletal muscle index} was independently associated with a 9% increase in the risk of non-cancer mortality"

"Muscle loss during ADT is occult, independent of weight change, and independently associated with increased non-cancer mortality in patients with high-risk prostate cancer."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/346...

Front Oncol

. 2021 Sep 17;11:722652. doi: 10.3389/fonc.2021.722652. eCollection 2021.

Muscle Loss During Androgen Deprivation Therapy Is Associated With Higher Risk of Non-Cancer Mortality in High-Risk Prostate Cancer

Pai-Kai Chiang 1 2 3 4 , Wei-Kung Tsai 2 3 4 5 , Allen Wen-Hsiang Chiu 2 3 , Jhen-Bin Lin 6 , Feng-Yi Yang 1 7 , Jie Lee 3 8

Affiliations expand

PMID: 34604058 PMCID: PMC8485032 DOI: 10.3389/fonc.2021.722652

Free PMC article

Abstract

The changes in body composition are early adverse effects of androgen deprivation therapy (ADT); however, their prognostic impact remains unclear in prostate cancer. This study aimed to evaluate the association between body composition changes and survival in patients with high-risk prostate cancer. We measured the skeletal muscle index (SMI) and total adipose tissue index (TATI) at the L3 vertebral level using computed tomography at baseline and within one year after initiating ADT in 125 patients with high-risk prostate cancer treated with radiotherapy and ADT between 2008 and 2018. Non-cancer mortality predictors were identified using Cox regression models. The median follow-up was 49 months. Patients experienced an average SMI loss of 5.5% over 180 days (95% confidence interval: -7.0 to -4.0; p<0.001) and TATI gain of 12.6% over 180 days (95% confidence interval: 9.0 to 16.2; p<0.001). Body mass index changes were highly and weakly correlated with changes in TATI and SMI, respectively (Spearman ρ for TATI, 0.78, p<0.001; ρ for SMI, 0.27, p=0.003). As a continuous variable, each 1% decrease in SMI was independently associated with a 9% increase in the risk of non-cancer mortality (hazard ratio: 1.09; p=0.007). Moreover, the risk of non-cancer mortality increased 5.6-fold in patients with SMI loss ≥5% compared to those with unchanged SMI (hazard ratio: 5.60; p=0.03). Body mass index and TATI were not associated with non-cancer mortality. Muscle loss during ADT is occult, independent of weight change, and independently associated with increased non-cancer mortality in patients with high-risk prostate cancer.

Keywords: androgen deprivation therapy; body composition; non-cancer mortality; prostate cancer; sarcopenia; skeletal muscle loss.

Copyright © 2021 Chiang, Tsai, Chiu, Lin, Yang and Lee.

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15 Replies
cesces profile image
cesces

Hmmmm

Makes intuitive sense once you think about it.

MateoBeach profile image
MateoBeach

Wow! Confirms my intuitive suspicions. Need to re-evaluate the risk benefits of ADT altogether.

maley2711 profile image
maley2711

This goes back to the basic question.......what IS the real benefit of ADT in terms of OS, in comparison to similar men with similar cancer who did not do ADT? 2 months, 2 years, or other? In other words, how much of the life-extending benefit of ADT is erased by the earlier mortality from other ADT-accelerated conditions? Is extension of life not the realistic goal...just avoidance Of PCa death?

in reply tomaley2711

If the average SMI decline >5% and for each 1% SMI decline non-cancer mortality goes up 9%, then it seems like 5 x 9 = 45%, pretty much totally eliminating the advantage of ADT. Unless ADT increases overall survival by > 45% as compared to no ADT. Prove me wrong.

On the other hand, some metastatic patients have no choice

maley2711 profile image
maley2711 in reply to

Not familiar with "SMI" and the source of calculation you are making? Hope you can provide some source for this? Thanks in advance!!!

in reply tomaley2711

From the cited study: “We measured the skeletal muscle index (SMI) ”. So the more that index went down, the more non-prostate cancer mortality went up. Which makes sense. Wasting away, etc.; everything is connected. “Pick your poison.” That said, I don’t know anything about the guts of the study

maley2711 profile image
maley2711 in reply to

I suppose we need to further narrow the OS time frame....5 yr OS, 10 yr OS, or ??? I don't have the exact number in mind, but , from what I've read, ADT added to radiation for at least unfavorable intermediate risk and higher risk does significant decrease PCa mortality compared to radiation alone....unfortunately for those patients in those risk groups. Then again, I might take another look at OS numbers for those groups and treatment, if such numbers available.

in reply tomaley2711

it looks like they were treated 2008-2018 and then followed for five years, presumably after each treatment. so it appears to be a 5 yr follow. The other thing we don't know is how hard each participant tried to work out, if at all. the devil's in the details

BrentW profile image
BrentW

I find this most alarming. I have been on ADT since 2004. Does this help explain why I tire so readily, and have so little strength compared to the Good Old Days?

Doesn't help those who are dependent on it for life, though. So what's the answer? How does this study impact treatment? Maybe consider a shorter term in high risk non-metastatic cancer?

London441 profile image
London441

Independently of pca or any other disease, strength and longevity are closely related.

Therefore, strength training is essential for older people.

Unfortunately, studies have shown only 25% of those over 65 exercise regularly, and 50% do not exercise AT ALL. This includes all forms of exercise, so then adjust for those who only walk, cycle etc (who unquestionably are healthier than the sedentary but are not addressing their strength).

In addition, ‘exercise’ is the vaguest of terms. The exact same activities are dramatically different dependent on level, intensity, duration and so forth.

The clamor for getting off ADT is very strong, either via shortening the initial course or taking holidays, and I get that. Lots of studies are cited on ADT’s harmful effects, I get that too. We know it’s bad.

However, at the end of the day we need to do what we can, what we have control over. Especially if our disease calls for treatment that attacks our strength but delays progression and death from metastasis, something we definitely want to avoid.

If we are on ADT we need to lift, as much and as often as we can. There is no other way to minimize that muscle loss. NO OTHER WAY!

Those of us who claim conditions that supposedly prevent from doing even low weight/high rep programs are mostly lying. We can always do something, very few exceptions to this.

If we are not on ADT, nothing changes! We still need to lift. It pains me when I see guys always bragging about what they used to do, citing injuries that prevent them from working out, how Covid closed their gym, pining for the ‘good old days’ etc. Especially those who are comparing to themselves of 10 or 20 years ago.

If you’re out of shape and you’re old 10 years ago may as well be another lifetime!

Decline of strength and cardiovascular fitness with age directly correlate to our habits. The less we do, the faster the decline. To lay this decline entirely at the feet of ADT if we are not consistently training is ridiculous.

Admittedly, it’s hard, harder still on ADT. Many men on ADT either don’t have the fortitude to lift, are too discouraged by their condition, don’t understand the seriousness, apathetic etc.

Again, there are exceptions. Advanced pca and it’s associated co morbidities have essentially crippled some. Yet these examples are very few in number.

If you are deconditioned, doesn’t take that much to get stronger and feel better, because the difference between low level and merely average is huge, much more than the gap between average/above average, high/elite etc.

OF COURSE muscle loss during ADT is associated with higher risk of non-cancer mortality! Mostly heart disease. And who wants to work hard to minimize that when you feel lousy and lose strength on ADT even if you do lift?

During my 18 months on ADT i did lose a little strength, and gained a little belly fat. I worked hard, and lost some strength anyway! My body eventually looked terrible to me, but all anyone could say was how fit I looked. I just kept in mind how much worse it would be if I gave in.

Now a year post ADT, I am admittedly feeling very differently. My T has risen from <10 to over 700. It’s nice to have hair on my legs again, and the night cramps are gone, and the ‘warm moments’ (mild hot flashes). I am clearly getting stronger and overall mental sharpness and energy are better.

However, I carry a strong imperative to not get attached to it. Enjoy every moment of the good feeling sure, but knowing full well I may have to get back on ADT at some point.

Weight bearing exercise should accompany all of us older guys, regardless of disease state, treatment side effects etc. There really is no other good choice.

BrentW profile image
BrentW in reply toLondon441

Thank you for this very encouraging post, London441.

London441 profile image
London441 in reply toBrentW

You’re welcome, and kind to say so. I always say variations on the same damn thing on this forum, but only because I truly believe it’s not talked about enough.

Always glad when my preaching is interpreted as encouraging, it’s definitely intended to be.

jfoesq profile image
jfoesq

From age 17 to my diagnosis 37 years later, at age 54, I gained 15 pounds of weight. After starting ADT at age 54, I gained 15 pounds in 6 WEEKS and eventually gained 20 pounds overall. I have also lost a lot of muscle mass and who knows how my bone density is doing? But- I am alive 9+ years later. And, although it's tough to get off my ass, I play a lot of tennis and I still go skiing every February, even with a knee replacement. My understanding is that without treatment I would have almost certainly died several yeas ago, perhaps 5-6 years ago. I am thankful and appreciative of my treatment and while I don't have the same feeling about the side-effects, I am more than willing to accept them niw, and hopefully for many more years into the future.

CAMPSOUPS profile image
CAMPSOUPS in reply tojfoesq

Well put.I/we can all relate to that and you communicated it well.

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