ADT paradox study.

This may be something worth posting on the Advanced Prostate Cancer forum on healthunlocked.com. Folks there would have a wider range experience on something like this.

I'm not sure that it means exactly that. I don't have the expertise to evaluate this fully, but it seems to be a study on individual cells (not humans) trying to refine the existing understanding of why even relatively-low levels of androgens are enough to stimulate castrate-sensitive PCa (which is why they try to get our testosterone as close to zero as possible in current treatments), but also in some cases, high levels of androgen might (more controversially) slow down advanced, castrate-resistant prostate cancer.

I don't think there are any clinical implications for us at this point — they're just looking at cells in a petrie dish, more-or-less — but they seem to have found some interesting nuances for researchers to follow up on and refine treatments in the future.

Thanks for sharing!

Hans, If you read this entire article and understood all the complex enzymatic processes being analyzed, you don’t belong on this forum….you belong in the front of a lecture hall of PhD candidates at a prestigious institute!😂
But seriously, I don’t think they were speaking to your situation as it is right now. They seem to be trying to understand why BAT therapy - switching between periods of ADT/no ADT and in some cases low doses of androgens (T) - works or doesn’t.
They talk about early and late stage AR signaling and how that might be useful and harnessed during BAT therapy to increase its efficacy. At least, that’s my take.
But again, this is something you may never have to worry about. I know you are concerned that your tumor grew in a low T environment, and that ADT might make it worse; however, science still doesn’t know for sure how much T is too much or too little - only castrate levels! Similarly, the genetic make-up of your cancer cells might make them able to proliferate at lower than normal levels of T.
That does NOT mean that your low androgen level CAUSED it to grow - in fact, it probably means that you need a longer time on ADT to eradicate it.

Thank you so much for your comments. I can assuredly assure you that I am just a concerned citizen looking for answers that I can’t seem to get from the attending oncologist. My hypothesis was that if this tumor was able to grow in a low testosterone environment, would it not because of that reality, be even more aggressive if T is eliminated? We all want to continue living, even non-desired entities.

Totally understand your frustration at not getting the answers you need. Sadly, your oncologist wouldn’t understand that article either, nor would many here in the US.
A lot of these scientific papers are “what if” theses. They are extremely obtuse and attempt to shed light on clinical observations which cannot be explained thru normal means, so must be looked at on a molecular level - far too technical for even the most learned oncologist, let alone you and me!
I too fell down the rabbit hole of reading articles - anything I could find- to help me in my treatment and help “guide” the clinicians….a fool’s errand. After reading about 50 articles similar to yours I finally understood that I had to let go and let the doctors do what they do.
I am happy that I did because all that research left me anxious, frustrated and totally exhausted. Best to you, Hans…
Phil

You’re right. It is a rabbit hole. I suspect that this, too, is one small step on the path leading to solutions that , perhaps, our grandchildren, should they find themselves in a similar situation as ours, might benefit. At least let not this disease go to waste

I think the confusion comes from use of the word "low."

What they mean is that prostate cancer can thrive EVEN in a low-testosterone environment, not EXCLUSIVELY in a low-testosterone environment.

In other words, prostate cancer can be feeding on testosterone even when your T is 3 or 4, not just when it's 20+.

I actually asked my oncologist about this at our last appointment in November, because my T had risen to 1.2, and he said that they don't worry about it feeding the cancer until it goes over 2.0 (normal range is 6.7 to 25.7 at my lab).

That’s the crux of the question. If this tumor was able to establish in a naturally low testosterone environment, wouldn’t cutting off the testosterone tap cause it find alternatives even more aggressively and thus, become more aggressive as a tumor - I.e more castrate resistant, and is ADT deprivation the right strategy? The consensus seems to be to follow dogma.

That seems highly speculative (and not, as far as I can tell, what the article you shared is suggesting). It's possible that they might discover anything in the future, of course.

In the meantime, the most-effective currently-proven way to delay or prevent castrate resistance is to combine ADT with a second-generation ARSI like Apalutamide or Enzalutamide.

I would agree that the article is NOT saying that. And “dogma” can sometimes be a good thing since in the medical field it is based on countless outcomes supported by facts.
It is KNOWN that testosterone can fuel prostate cancer; it is KNOWN that Prostate cancer can become castrate resistant.
But if you don’t follow the dogma - the facts - what would be your alternate course of action? No ADT? T supplements for a highly speculative already castrate resistant strain of PCa? No doctor would ever agree to that.
May I make a suggestion? Why not go with the dogma for now and see what happens. If your PSA drops and stays very low during the course of treatment, you’ll absolutely know that you are on the right path. If, however, your PSA starts to noticeably rise you can then make the course correction - if your doctors agree - to take an ADT holiday and see if the PSA comes down….or goes even higher. That can happen as well.
You are not going to cause yourself to have a fatal outcome by going on ADT for a short period of time, if that is your main worry.