Marnie passed me some solid information on the APCCC...and it is all about testosterone... I got you looking now !!!
First, the warmup with a case study and the message that when it comes to testosterone recovery, short term ADT can take 18 months and long term ADT to 2 years for recovery...while Relugolix (Orgovyx) was 60 days..
A study covering the use of Abiraterone vs Abiraterone plus Firmagon vs Firmagon alone showed faster testosterone recovery in the abiraterone alone group..
In the EMBARK trial2 assessing enzalutamide + leuprolide versus enzalutamide versus leuprolide in high-risk non-metastatic hormone-sensitive prostate cancer, during treatment suspension in the combination group and the leuprolide-alone group, testosterone recovered slightly, but not to baseline levels. There was very little effect on testosterone in the enzalutamide monotherapy group.
Dr. Blanchard summarized this section of his talk discussing testosterone recovery with the following statements:
Agonists: 6-24 months after end of treatment
Antagonists: 1-6 months after end of treatment
There is no impact of concurrent abiraterone or ARPI
Radiotherapy by itself can lead to testosterone decrease and MORE...
They are just used to me putting up stuff with outrageous headlines...
I think the take home message is that the best MOs on the planet are looking at testosterone recovery and what can be done to facilitate that recovery post ADT... it is becoming all about prolonging hormone sensitivity and qol...
I guess this is where we que Bob Dylan singing, "The times they are a changing..."
This is a very interesting post in terms of a rhetoric and anthropology of testosterone recovery. Which might however avoid medical reality.
So I have a serious question. What are the implications for longevity, longevity with lucidity and functionality, of achieving testosterone recovery in circumstances of non-metastatic prostate cancer?
I am afraid that making a decision to enjoy a return to testosterone living may result in a shortened lifespan. (I suppose this concern can be complicated by the whole idea of "BAT", in the most general sense of stopping and starting ADT or even doublet therapy, the better to forestall resistance. Maybe by allowing recovery of testosterone, we maybe interfering with the progression to resistance?? In which case testosterone recovery might be a very good thing?)
I see a lot of posts on this forum where return to "what was" is the most important thing. On the other hand, once in a while we see someone who says "I accept where I am now and I'm not interested in dangerous experiments and holidays." I am in this category myself.
This can be boiled down to two questions.
1. RISK - Are the programs outlined in the shared document above potentially risky in terms of overall life expectancy?
2. REAL CHOICE - If so, is this risk clearly presented to prospective participants in such a program?
My concern is that a return to testosterone living is risky, even without metastasis, and that this risk may be properly highlighted to the men considering the question. I also get a sense, in terms of rhetoric, that there is advocacy around return to testosterone living.
I would be delighted to find out that my concerns are not necessary.
Check one of my latest posts. They are doing a trial exactly to check if great responders to adt and arsi can do an intermittent regime (not BAT, just suspend therapies). We will know the risks hopefully soon. Till then I also think I will stay on the safe side 😀
Everyone travels their own path....at this point, the science lacks the information on biomarkers, and so, there are no guarantees... Whatever path a person chooses.... it is not a wrong path, but it is the right one for them... We are n=1 in MHSPC.... "Testosterone is the Devil in advanced prostate cancer, didn't you know that, mister??"
The Science is dragging a--, IMHO... the discoveries are coming, and we lack the ability to ID what is best for each patient based on genetic testing/ biomarkers, etc... The discoveries are coming... and yet, we lack the ability to utilize them to the next stage--CRISPR--could some gene splicing turn cancer into a chronic disease as compared to possible death.???
What we need are answers, JITM... and the Science is unable to keep up with itself... Science is chasing its tail... Does the benefits of T on heart attack, stroke, bone health, etc in MHSPC patients make a case for doing BAT at the risk of an aggressive recurrence??
Even if I had that answer, it would not make me a moderator on this forum....lol..
At this point, risk vs real choice is a fairy tale in MHSPC, because BAT exists only for MCRPC... and The FPC BAT men, who share their experiences... The clinical trials... in a place in the distant future... your answer--5 to 10 years or more away...
There is no right or wrong path on your journey... it is just... your journey...
Super thanks NP for your very lovely and thoughtful post. And you have highlighted that elusive goal that metastatic prostate cancer should become chronic instead of terminal.
Also I think you've done a good job of almost poetically summarizing where we are today. What you are saying is that our choices are hardly choices. We don't know enough yet to have anything other than muddled choices.
I do have an issue with the whole crowd who want to turn back the clock and take ADT holidays. I think this is indeed risky.
And I see all the different weird treatments including exotic radiation and radioligand therapies and ever-fancier surgeries etc, and very complicated immune system and gene-based therapies and whatnot.
From what I can tell, all this whack-a-mole doesn't give you a lot of extra time.
Of course heaven forfend I develop progression and resistance and maybe I'll want to try something more exotic too! It is comforting to a note that progress and improved therapies for metastatic prostate cancer seems to be real.
Lastly, your highlight of the nasty side effects of standard ADT etc. such as cardiovascular disease and brain fog and bone fractures etc is important. My own opinion on this is that there isn't as much strategic attention on PCa therapy side effects as there should be, other than a "prescription for Denusomab" etc.
I have no big conclusion here. Just that I wanted to engage with your note because I liked your message and how it was expressed.
I'm glad you enjoyed the post, but when it comes to MDT (what you call whack a mole), radioligands, oligometastatic state, and intermittent ADT, well, we are worlds apart...
If you believe in continuous ADT(which you do), can you explain to me what cells are left after years of treatment?? If they are resistant cells, then utilizing MDT to eliminate resistance is logical... after all, how do other tumors learn resistance or gain in resistance..?? mRNA is the most likely source from resistant tumors... or do you disagree?? In other words, remove the source of resistant information...
If you agree with my mathematical formula, that:
CDS= m MT + MT
Cancer disease state equals micrometastases (invisible) + metastases (visible)
Then tell me, which provides the greater tumor burden and mutational burden...??
Metastases (Visible) or micrometastases (invisible)...??
I know some posters will say there is no proof by OS in using MDT, and yet, they know that in PCa, it takes 10 years or more to prove OS... so why even bring it up??
For me, IADT makes sense, because my initial tumor burden was low, and I hated the side effects of ADT--brain fog, hot flashes, fatigue, anemia, etc...With you, a PSA of 1700, and significant disease, continuous makes sense..
Our disease is heterogenous, and so...why should one size fit all??`
I just read your interesting reply now. And I have a few questions and comments.
1. I think MDT means metastasis directed therapy?
2. One could say then that my triplet therapy and ongoing doublet therapy is MDT. Because of the micro metastases or any metastases, the meds are hitting them all.
3. You are absolutely correct to highlight the problem of progression or evolution. After all this extreme selection pressure the cells that are left will be the foundation of resistant PCa. And then what does one do?
4. You said something very interesting about mRNA. I think it was that the dangerous new generation of resistant PCa cells are the source of information for killer metastases. And that a more flexible therapy strategy, MDT, is the way to either get them or even prevent them from developing.
I'm two and a third years in, from diagnosis. Wasn't expected to be here and started with an act of referral to palliative. They're great people but hopefully I won't need them for a while.
Thanks DD for the references. I am starting to read them - will take a while. I wasn't surprised to see the abscopal effect mentioned - I have heard that this is a controversial issue although I find it interesting.
It crosses my mind that this whole discussion is similar to the idea in nature that there are reservoirs of disease for birds etc. and then I guess if you irradiate the mass or something then that source of new cancer cells would be eliminated. Or something...
Reservoirs of disease...like senescent cells...?? there is some of that, but I believe that in the case of treatment with proven resistance, that MDT can make a difference--see the K9 Terror's post below:
"or something"..???? Not sure what that is, but I say some believe and some don't... each plans his journey with whatever logically makes sense, reads, and hopefully, has a good MO/RO to guide them..
Enjoy the FPC readings...May you find good guidance on your journey ...
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Genistein potentiates the radiation effect on prostate carcinoma cells