The paradox of testosterone and ADT

Interesting hypothesis. I posted earlier about low (ish) PSA of 0.33 seventeen yrs post RARP and no further tx. At PSA0.33, PET showed 3 nodules + ‘micronodules’ on lungs but no where else. High burdrn? Testosterone 745 pre ADT. I keep wondering if this ca has already transitioned to neutoendocrine and thus not dependant on T, or wouldnt PSA be higher? Hate to start ADT when the cancer isnt dependant on the T. I have asked why not further test the biopsy for androgen receptivity to be sure, but sounds like no further testing is being done. What are anyone’s thoughts on my thinking - am I way off or missing something? It seems like this cancer has had 17+ years to mutate already.

Having the cancer come back after 17 years is not unique. At the advanced prostate cancer Ancan.com Weekly online meetings, we frequently see people who have gone many years without any issues after surgery, and the cancer comes back. Recently had somebody who Had it come back after 30 years.

Why is there no test for ADT receptivity, It really isn’t needed since within a month of taking it. The PSA drops dramatically within two months. It usually drops to undetectable. That also stops the growth of any metastasis that have shown up, And frequently shrinks the size of them. Another thing that is done when it comes back is to include a second drug like Zytiga or one of the lutamides.

Lung metastasis seem to be the hardest to treat. I know a few people with them that have tried many different treatments, but they are still there, though in some cases, they reduced in size.

You might Talk to your doctor about having Pluvicto. It can greatly reduced the size of metastasis all over the body, Though it only works really good with 1/3 of the people and OK with 1/3. They have approved doing it before chemo.

So, then, what happens if your prostate tumor grew in a naturally low testosterone environment and hence learned how to draw nutrients from sources other than testosterone? That would make the treatment with ADT counterproductive, as it would entice the tumor to become even more aggressive. The questions I have: "How do you find out?", and "How do you deal with this?". all the while "dealing with the reality one is dealing with a dogma-driven oncologist"

I read this in another study. The study examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC (castrate resistant) development, in 387 patients who were treated with CAB (combined ADT) for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. The study designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8.
The 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached).
Conclusions
The time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities.

I know what you are saying, Hans, but you positively KNOW in 30 days if your cancer is ADT sensitive.
My T went from around 625 to 5 - FIVE! in one month. If it did not, drs would have probably given it another month to see if it stayed the same, decreased or even increased. Only THEN would they have changed the regimen, which works 99.99% of the time.
Is 30-60 days an unreasonable amount of time in the greater scheme of things?
Do you feel that 30-60 days in the “wrong” direction irreversibly dooms you to treatment failure?
You and I have debated these points before and it all comes down to genetic testing, although I have never had it done myself.
Is there even a genetic test which shows ADT response and effectiveness? I don’t know but it doesn’t seem that it should be all that difficult.
And as for the questions posed by @dpfbanks, is it not possible that your husband’s pretty darned high T levels are a potent source of his cancer’s fuel? I mean 745 is robust to say the least and could be the obvious culprit hiding in plain sight, no?
Occam’s Razor tells us that the simplest theory is usually the correct one….
Phil

So, then, what happens if your prostate tumor grew in a naturally low testosterone environment and hence learned how to draw nutrients from sources other than testosterone? That would make the treatment with ADT counterproductive, as it would entice the tumor to become even more aggressive. The questions I have: "How do you find out?", and "How do you deal with this?". all the while "dealing with the reality one is dealing with a dogma-driven oncologist"

I know what you are saying, Hans, but you positively KNOW in 30 days if your cancer is ADT sensitive.
My T went from around 625 to 5 - FIVE! in one month. If it did not, drs would have probably given it another month to see if it stayed the same, decreased or even increased. Only THEN would they have changed the regimen, which works 99.99% of the time.
Is 30-60 days an unreasonable amount of time in the greater scheme of things?
Do you feel that 30-60 days in the “wrong” direction irreversibly dooms you to treatment failure?
You and I have debated these points before and it all comes down to genetic testing, although I have never had it done myself.
Is there even a genetic test which shows ADT response and effectiveness? I don’t know but it doesn’t seem that it should be all that difficult.
And as for the questions posed by @dpfbanks, is it not possible that your husband’s pretty darned high T levels are a potent source of his cancer’s fuel? I mean 745 is robust to say the least and could be the obvious culprit hiding in plain sight, no?
Occam’s Razor tells us that the simplest theory is usually the correct one….
Phil

https://www.mdpi.com/2402756

"..I know what you are saying, Hans, but you positively KNOW in 30 days if your cancer is ADT sensitive. My T went from around 625 to 5 - FIVE! in one month."

So the T goes down fast, which makes complete sense.. And what about the the tumor response to the lowered T? Did your tumors shrink and PSa go down as well? That is the plan and hopefully your result. Its also the question I keep dancing with because of the Duke study on T slowing growth in advanced prostate cancer. Does the lowered T reduce the prostate cancer in all cases, or might it let the ca have a field day in some rare cases? Teting for androgen receptivity might help pre-ADT...so it seems.