androgen receptor inhibitor for nmCRPC

So if you become castration resistant.

Your PCa will grow without androgen.

Your MO will recommend an androgen receptor inhibitor.

Why bother inhibiting PCa androgen receptors if it can survive without androgen??

Confused.

[Tall_Allen]

It can grow without androgen, but it will grow much faster with androgen.

[Hidden in reply to Tall_Allen]

But the Lupron etc takes care of the androgen.

So no androgen.

PCa becomes castrate resistant. It grows without the need for androgen.

Why block androgen receptors?

[Tall_Allen in reply to Hidden]

Testosterone is not the only androgen. Plus the upregulation of the androgen receptor means that it can be activated by ligands other than traditional androgens. It is best to block it while it is still external (blockable).

[Hidden in reply to Tall_Allen]

Thx, just increasing my knowledge for the future.

But, Im sure my radiation treatments will "cure" me 🙄

[K-xo in reply to Tall_Allen]

Great question and great answer. Correct me if I’m wrong TA, but I think what you’re saying is you want to minimize the fuel?

[Tall_Allen in reply to K-xo]

Yes.

[spencoid2 in reply to Tall_Allen]

I am still con fused. I have had orchiectomy and was on aberaterone. PSA started rising continuously. MO recommended chemo and stopped the aberaterone. Does it make sense to stop it and not replace it with anything? He said it was stopped because it stopped working.

[Tall_Allen in reply to spencoid2]

If it stopped working then why take it? But why not try enzalutamide with docetaxel, like this:

prostatecancer.news/2022/10...

[spencoid2 in reply to Tall_Allen]

thought that it might be still working partly. will ask MO about enzalutamide but chemo is done for now

[Vynbal in reply to Tall_Allen]

What does "abiraterone stopped working" mean? If it means that the adrenal gland has returned to producing androgens despite the abi, then yes, what is the point of continuing the Abi. But if it means that the PCa is still growing despite the lowered Androgens due to the Abi then why would not the same logic apply as to 1st gen ADT, ie reducing the fuel? IOW, if the PCa is still growing with Abi, won't it grow faster without Abi?

[Tall_Allen in reply to Vynbal]

I understand your point, and thought similarly. Only they found that combining enzalutamide+abiraterone+ADT was no more effective at slowing progression and improving survival than enzalutamide+ADT alone.

ascopubs.org/doi/10.1200/JC...

But perhaps it would work better combined with apalutamide?

The ACIS trial found a strong PSA effect of the combo, but no survival difference except in men >75:

practiceupdate.com/news/324...

One problem with combo treatments is drug toxicities increase. Maybe the benefit in controlling the cancer is countered by the drug interactions and toxicities?

[ADTMan]

There are 3 different types of prostate cancer cells. The most common use endogenous testosterone produced by the body. There are cells that produce their own testosterone. The third type don't need testosterone. Thus, when castration resistance occurs, the cancer is composed of type 2 and 3 cells. Drugs which block the androgen receptor work on type 2.

[LowT]

Seems this might make case for use of 5-alpha reductase inhibitors. At least a trial.