elimination of testosterone through ADT and aggressive behavior

Posted by hans_casteels @hanscasteels, Feb 28 6:31pm

I wanted to solicit your thoughts on something that has been on my mind regarding my treatment. I started Firmagon 2months ago, PSA went from 26.7 to6.7. Had Brachytherapy last Tuesday, EBRT to follow. Don't know current PSA levels - I assume they'd be lower.

Given that my prostate cancer developed in a naturally low-testosterone environment, I was wondering whether complete androgen deprivation through ADT could push the tumor to become more aggressive in its attempt to survive. Specifically, could eliminating testosterone encourage the cancer to adapt by finding alternative growth pathways, such as increasing androgen receptor sensitivity or relying on other metabolic sources?

I ask because, after two Firmagon injections, my PSA has only dropped to 6.7, which seems slower than expected. Could this be related to the tumor already being adapted to a low-testosterone state, or is it within a reasonable range at this stage of treatment? Would this have any implications for how we monitor PSA trends or consider additional therapies down the line?
I appreciate your time and any insights you can share. Looking forward to our next appointment.

Thank you again, as always, for the audience's advice and wisdom. Patience is not a strong point for me.

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heavyphil | @heavyphil | Mar 2 11:58am

In reply to @hanscasteels "It’s the 25% that worry me. Those are the cells, probably, that represent the next stage." + (show)

My God, I never thought I would meet someone with a more pessimistic view than me!! Must admit, you see the glass even emptier than I do….😳
The “0ther 25%” is getting a nasty dose of radiation, some of which you’ve already gotten. ADT was never going to bring your PSA down to zero, or even close. You have a tumor, remember?? Let the radiation do its thing before you start imagining the next steps, OK?

hans_casteels | @hanscasteels | Mar 2 12:29pm

In reply to @heavyphil "My God, I never thought I would meet someone with a more pessimistic view than me!!..." + (show)

We could discuss where the “pessimist” and “realist” lines are.

heavyphil | @heavyphil | Mar 3 6:51am

In reply to @hanscasteels "We could discuss where the “pessimist” and “realist” lines are." + (show)

Sure….You go first…

hans_casteels | @hanscasteels | Mar 3 9:11am

In reply to @heavyphil "Sure….You go first…" + (show)

Of course.. a pessimist sees the diagnosis as a death sentence; a realist sees it as a challenge with odds, strategies, and room for maneuvering. I am not at all concerned about the positives. I want to understand the odds and timely approaches to those elements that will play a role in the future if they’re not addressed today or soon. That, I think, does not make me a pessimist. Your thinking is exactly why companies and governments fail in risk management: the obvious isn’t going to be an issue, it’s the non-obvious that’s going to (as is so clearly stated in American English) - bite your ass.

heavyphil | @heavyphil | Mar 3 11:26am

In reply to @hanscasteels "Of course.. a pessimist sees the diagnosis as a death sentence; a realist sees it as..." + (show)

OR…..the non obvious possibility that you die from a heart attack or stroke? Or a jealous husband coming home from work early? Choking to death on a healthy carrot stick? The possibilities are endless….
My ability to manage risk as far as cancer is concerned is almost nil at this point. I’ve GOT it. All the organic food, supplements and exercise - while good in general - were not good enough in particular to avoid this disease. So now I treat it, one logical step at a time.
So if you feel that you are managing risk by conjuring up scenarios - and hypothetical solutions - which will probably never happen in the real world, you are going to be anxious, frustrated and exhausted.
Take it easy until you know more…
Phil

kujhawk1978 | @kujhawk1978 | Mar 4 8:21am

I have read some studies relating to low testosterone and aggressive PCa.

Keep in mind I am not a trained, educated, board certified or licensed medical person, just a fellow member of this club none of us asked to join, trying to make sense of it

The layman's version, our PCa is made up of heterogenic PCa cells, some die off in a low testosterone environment, others adapt, the old "selection" discussion. Thus the discussion about continuous versus intermittent and resistance, adding ARIs to stop those PCa cells wo are still around because they adapted to low T environments.

The selection discussion as I understand is behind the addition of ARIs. and at the heart of why we use combined versus monotherapy.

Some things to think about:

What was your starting T?
Once you started, has your T dropped to < 20?
Outcomes are different between radiation and ADT therapy in terms of PSA, with ADT my understanding is one wants PSA to be undetectable when on ADT, with radiation, you are looking for a "nadir."

A key prognostic indicator of treatment "success" and prognostic for terms such as progression free survival, overall survival, radiographic free survival, is one's PSA reaching undetectable within the first six to nine months when using ADT.

The clinical data you describe indicates a reasonable degree of success at this point, as others have said, stay the course, assess and then decide based on the clinical data, what's next.

stu6060 | @stu6060 | Mar 5 11:11am

You sound like a problem solver by training or natural instinct. I have no answers for you. I had my prostate taken out 17 years ago (at 46) and no my PSA is creeping up. So I find myself in the same situation as you are in regarding considering treatments and outcomes. I certainly don't regret the time I spend researching and considering options. Physicians are busy ,, there are choices in treatments. Knowledge is power. All the best to you and everyone else here.