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I want to talk about why we haven’t been able to increase muscle mass in prostate cancer, what we can do about it, and why this might be OK.
Grab a coffee if you want, this is a long thread. It’s also full with some hot takes, so there’s that. 1/
Grab a coffee if you want, this is a long thread. It’s also full with some hot takes, so there’s that. 1/
1.This meta that @Moritz_Schumann was involved in pretty much sums up what’s been done so far. Resistance training interventions anywhere from 12 weeks to 6 month show little if any meaningful improvements in muscle. Before you yell about the 0.7kg – we’ll talk about that 2/
Link to FT ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618665/)
First, some methodology/design considerations, then some fizzy-ology.
1. MEASUREMENT I’ve been lucky to have learned a lot from @KrissyKendall1 and @DrJordanMoon over the years about body composition and its measurement. 3/
First, some methodology/design considerations, then some fizzy-ology.
1. MEASUREMENT I’ve been lucky to have learned a lot from @KrissyKendall1 and @DrJordanMoon over the years about body composition and its measurement. 3/
The body is divided into compartments, depending on what method you use, you can get an estimate of less or more of these compartments.
Importantly, constant hydration, when in fact total body water can change ~8-9% a day. 4/
Importantly, constant hydration, when in fact total body water can change ~8-9% a day. 4/
DXA is not perfect, and can be profoundly influenced by hydration, muscle glycogen = errors in estimate of how much muscle.
Add individual responses to exercise programs and I'm not convinced..
https://twitter.com/AaronHengist/status/1247095131393667072
https://www.karger.com/Article/Fulltext/445510
5/
Add individual responses to exercise programs and I'm not convinced..
https://twitter.com/AaronHengist/status/1247095131393667072
https://www.karger.com/Article/Fulltext/445510
5/
A lot of the studies using DEXA don’t control for hydration and don’t post any pre-post standardisation measures. So, without knowing that these factors were controlled for in individual studies, I wouldn’t be hanging my hat that meaningful changes in muscle have occurred. 6/
So, my interpretation is the same as Chen et al - I'm not convinced we've clearly demonstrated that we can meaningfully improve muscle mass in prostate cancer. Now, let's move to the why 7/
WHY– Principles of training
@KLCampbellPhD @sarah_ns_phd & @winters_stone have showed poor attention to principles of training in ExOnc. If you want to improve muscle & your protocol isn’t designed with things like progression & overload, you’re gonna have a much harder time. 8/
@KLCampbellPhD @sarah_ns_phd & @winters_stone have showed poor attention to principles of training in ExOnc. If you want to improve muscle & your protocol isn’t designed with things like progression & overload, you’re gonna have a much harder time. 8/
Link to FT above( https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30953460/)
So is a lack of effect from a lack of efficacy of an exercise program, or a result of a suboptimal training program? Probably a combination of both.
Next, a hot take on logistics? 9/
So is a lack of effect from a lack of efficacy of an exercise program, or a result of a suboptimal training program? Probably a combination of both.
Next, a hot take on logistics? 9/
WHY - Logistics
Large trials, multiple sites, different equipment, different staff, different settings, different expertise, hospital politics and restrictions. We have an ideal best-case scenario of how we would like this to look. 10/
Large trials, multiple sites, different equipment, different staff, different settings, different expertise, hospital politics and restrictions. We have an ideal best-case scenario of how we would like this to look. 10/
Often times, a lot of this this work happens in hospital clinics, with minimal staff, low budget etc. This can dramatically affect the “quality” of the training stimulus someone receives. This is the fine balance between in house RCTS and the “real world” application. 11/
Likely, the latter is a more accurate reflection of what we can expect, as not many are going to have access experts that understand their disease, treatment & have the background in RT to design/run a strong prog. So maybe, these are a better reflection of the true signal? 12/
WHY - Dose
Getting someone from sedentary to 3x/wk stressful RT is hard. Even harder when you through all the stuff that comes with a cancer diagnosis (emotional/financial burden, appointments, illness etc) on top of it. We tried to expand on this in our understanding of..13/
Getting someone from sedentary to 3x/wk stressful RT is hard. Even harder when you through all the stuff that comes with a cancer diagnosis (emotional/financial burden, appointments, illness etc) on top of it. We tried to expand on this in our understanding of..13/
..what we mean by adherence and compliance to exercise. There is a diff in what we think happens – everyone is getting close to prescribed dose, & progression of training. The reality is a lot of missed/modified sessions due to illness, appointments, fatigue, pain etc. 14/
All of which are a natural occurrence in cancer. This makes the hill to adaptation harder to climb.
We haven't even got to treatment effects yet!
WHY - Androgen Deprivation Therapy.
ADT results in castrate levels of testosterone in folks receiving it.
15/
We haven't even got to treatment effects yet!
WHY - Androgen Deprivation Therapy.
ADT results in castrate levels of testosterone in folks receiving it.
15/
This brings about some pretty brutal side effects on body comp, that tend to be associated with how you receive it and how long you’re on it. *Pay attention to fat mass below – this is important and we’ll talk about it later. 16 /
Couple ADT with physiological changes with age (denervation of type II muscle fibers, reduced satellite cell content etc.) and we’re starting to understand why 12 weeks of training may not result in much changes. 17/
@TSNils demonstrated even at cellular level, what we typically expect from RT may not occur in prostate cancer. (Ask him about this, any deeper on muscle biology and I tend to panic sweat). ( https://onlinelibrary.wiley.com/doi/abs/10.1111/sms.12543) 18/
WHY - Comorbidities and injuries.
We’re dealing with folks ~40s-90’s in this pop. So, on top of cancer and ADT, we have pre-existing torn rotator cuffs, herniated disks, bum knees, diabetes, COPD etc. This makes ExRx very challenging! 19/
We’re dealing with folks ~40s-90’s in this pop. So, on top of cancer and ADT, we have pre-existing torn rotator cuffs, herniated disks, bum knees, diabetes, COPD etc. This makes ExRx very challenging! 19/
Modifying ex around these might mean that folks literally can’t handle a training load sufficient for adaptation! Want a homogenous population and exclude people with any of the above? Cool, good luck getting enough participants to run a trial. 20/
This is the reality of working with this population and what makes it so rewarding!
So, it turns out, we might have a much bigger task on our hands at trying to increase muscle mass than we might have originally thought. Inherently, we now ask - is exercise enough? 21/
So, it turns out, we might have a much bigger task on our hands at trying to increase muscle mass than we might have originally thought. Inherently, we now ask - is exercise enough? 21/
This is probably one of the more exciting areas, with a lot of folks recognising that combining exercise with diet/supplementation *should* give us a better shot at this!
Some examples are @ChristinaDieli looking at protein supplementation with RT
( https://pubmed.ncbi.nlm.nih.gov/29614993/ ) 22/
Some examples are @ChristinaDieli looking at protein supplementation with RT
( https://pubmed.ncbi.nlm.nih.gov/29614993/ ) 22/
We are looking at creatine suppl with RT to see if what happens. ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756416/)
I think anyway we can offer nutritional support to training programs, we're giving everyone a much better shot -
A BIG area of future res (though even then it might not be enough)23/
I think anyway we can offer nutritional support to training programs, we're giving everyone a much better shot -
A BIG area of future res (though even then it might not be enough)23/
DOES IT MATTER
Why do we care about this? The biggest concern for men with prostate cancer after ADT is the trajectory towards frailty, dependent living and ultimately mortality. So, anything we can do to possibly delay this, will be important. 24/
Why do we care about this? The biggest concern for men with prostate cancer after ADT is the trajectory towards frailty, dependent living and ultimately mortality. So, anything we can do to possibly delay this, will be important. 24/
BIG point here - DELAYING decline is not the same as increasing. This is going to be important in the next few tweets but I would say that MAINTAINING muscle mass is as/more important in aging and disease than increasing it. 25/
So the fact that even though it might not increase, we can prevent decline, is a win for me!
Remember FM? Double check this picture below and look at changes with body comp over time.
Are health risks of ↑ fat mass is “worse” than ↓ FFM? 26/
Remember FM? Double check this picture below and look at changes with body comp over time.
Are health risks of ↑ fat mass is “worse” than ↓ FFM? 26/
Worst case scenario is both, the ole' sarcopenic obesity – no good for anyone!
So maybe then, we shift focus towards maintaining muscle and decreasing fat mass? 27/
So maybe then, we shift focus towards maintaining muscle and decreasing fat mass? 27/
We did some pilot work in this space at @OhioState_EBML and are looking at expanding this trial (NIH GIVE US MONEY!) to try an answer this some more in the coming years.
( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361261/) 28/
( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361261/) 28/
Then after ALL THAT, we still need to look at strategies to help foster the maintenance of activity (and changes in body composition) over time.
Changes in a 12-week trial are irrelevant if folks aren’t still something months/years from now. 29/
Changes in a 12-week trial are irrelevant if folks aren’t still something months/years from now. 29/
We're going to need experts from different areas to come up a blend of training hard enough for changes to occur, but in a way that makes you want to keep doing it.
Probably the hardest part of this piece - behavioral interventions are intense and require A LOT of work. 30/
Probably the hardest part of this piece - behavioral interventions are intense and require A LOT of work. 30/
Side note - is your a physiologist and look down on/don't appreciate how hard behavioural research is, well you're an idiot 31/
Summary - We haven't been able to increase muscle mass in prostate cancer yet, and that's OK.
There's some things we can do to improve/build on what we know.
There's also a strong argument to be made that if you can maintain muscle mass, increase strength.. 32/
There's some things we can do to improve/build on what we know.
There's also a strong argument to be made that if you can maintain muscle mass, increase strength.. 32/
and physical function, drop fat mass a bit - that might be a more well-round approach.
TL:DR - treatment for prostate cancer sucks and we need to try find ways to combat the side effects. 33/
TL:DR - treatment for prostate cancer sucks and we need to try find ways to combat the side effects. 33/
Would love to hear other peeps thoughts on this and point out anything I got wrong or missed! If there’s enough interest, I might put together a presentation on it too.
Thanks for coming to my Ted talk.
*Jordan and Krissy, I know I KNOW, it's not "muscle", but you know twitter
Thanks for coming to my Ted talk.
*Jordan and Krissy, I know I KNOW, it's not "muscle", but you know twitter
