Characteristics of BAT responders

[Tall_Allen]

Johns Hopkins retrospectively identified genomic characteristics of the best responders to Bipolar Androgen Therapy. They identified 22 men across all their trials (19% of 114 men across several trials) in mCRPC men who responded very well (≥ 70% PSA reduction). They were able to get somatic genomic tests of tissue samples from 15 of them. All 15 "deep responders" harbored a pathogenic mutation in TP53 (a tumor suppressor gene) and/or a homologous recombination DNA repair (HRD) gene. In such patients, their cancer didn't progress for almost a year. As we've seen, that increase in progression-free survival doesn't translate into overall survival.

clinical-genitourinary-canc...

The next step would be to prospectively select patients with such mutations and treat them with BAT. We saw last week that response to BAT+PARP treatment did NOT depend on DNA repair defect status, so it is not at all certain that these are the (so far) elusive biomarkers for BAT success. Also, I hope they will do a similar analysis of the worst responders.

[cesces]

Oh wow. Thank you again Tall_Allen

Don't you dare age out on us. Lololol

Just to make sure I understand what you said.

If you have a TP53 mutation, there are some early indications that BAT therapy may work for you, or is at least worth taking a closer look.

Do I have that right?

[Tall_Allen in reply to cesces]

Well, it's the other way round. If BAT worked really well for you, it is likely you have one of those mutations. Of course, having those mutations increases your risk of dying of PCa sooner, so it it undesireable to have them.

[cesces in reply to Tall_Allen]

That they are making progress with BAT targeting is good for everyone, those for whom it works, and those for whom it doesn't.

[Tak-Druk]

Thanks... I really appreciate your contributions of information and analysis to keep us informed of these kinds of developments. I appreciate it from many here, but I feel like you go further and you're information is presented in a pretty consistent and reliable Tall_Allen. It may not even always apply to me personally in the moment, but it fills out a larger map of my understanding of the terrain I am in.

[Tall_Allen in reply to Tak-Druk]

Thanks - I try to be accurate while translating from medicalese. I think it's important to be measured too, although some would wish for more black-and-white conclusions.

[Jbooml]

How do you compare BAT with estradiol or otherwise like treatments, I realize restoring T levels is highly prized but if we can fool the AR mechanisms by alternative ‘replacements’ while keeping PC at bay can we hope for more normal lives spared pesky if not destructive SEs.

[Tall_Allen in reply to Jbooml]

Interesting idea! U of Colorado is using transdermal testosterone for BAT, so it is theoretically possible to alternate transdermal testosterone with transdermal estrogen, but I've never seen that tried.

[Scout4answers]

theoretically possible to alternate transdermal testosterone with transdermal estrogen,

Allen

This is an interesting idea, can you flesh out why you think this may have some potential.

My understanding of the role of estrogen in PCa is lacking.

[Tall_Allen in reply to Scout4answers]

The Patch/STAMPEDE trial of transdermal estradiol will prove (I expect) that transdermal estradiol is equally effective to a GnRHagonist. They have already proved that it suppresses testosterone with fewer side effects.