Determinants of PSA Response to Bipolar Androgen Therapy [BAT]

[pjoshea13]

New study from Sartor et al below [1].

"Bipolar Androgen Therapy (BAT) is a novel therapy known to be effective in a subset of men with metastatic castrate resistant prostate cancer (mCRPC)."

"Twenty five patients were non-responders and 16 were responders. Baseline characteristics between non-responders and responders varied. Responders were more likely to have had a radical prostatectomy as definitive therapy and were more likely to have been treated with an androgen receptor (AR) antagonist (enzalutamide or apalutamide) immediately prior to BAT (compared to abiraterone). Duration of prior enzalutamide therapy was longer in responders. Non-responders were more likely to have bone-only metastases and responders were more likely to have nodal metastases. Assays detected ctDNA AR amplifications more often in responding patients. Responders trended toward having the presence of more TP53 mutations at baseline."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/369...

tate. 2023 Mar 23. doi: 10.1002/pros.24529. Online ahead of print.

Clinical and Molecular Determinants of PSA Response to Bipolar Androgen Therapy in Prostate Cancer

Sydney A Caputo 1, Madeline Hawkins 2, Ellen B Jaeger 2, William Fleming 1, Crystal Casado 1, Charlotte Manogue 2, Minqi Huang 2, Alex Lieberman 2, Malcolm Light 2, Isabelle P Sussman 2, Patrick Miller 2, Pedro C Barata 1 2, Brian E Lewis 1 2, Jodi Lyn Layton 1 2, Elisa M Ledet 2, Emmanuel S Antonarakis 3, Oliver Sartor 1 2

Affiliations1Tulane University School of Medicine, New Orleans, LA.2Tulane Cancer Center, New Orleans, LA.3University of Minnesota Masonic Cancer Center, Minneapolis, MN.

PMID: 36959766 DOI: 10.1002/pros.24529

Abstract

Background: Bipolar Androgen Therapy (BAT) is a novel therapy known to be effective in a subset of men with metastatic castrate resistant prostate cancer (mCRPC). A better understanding of responders and non-responders to BAT would be useful to clinicians considering BAT therapy for patients. Herein we analyze clinical and genetic factors in responders/non-responders to better refine our understanding regarding which patients benefit from this innovative therapy.

Methods: mCRPC patients were assessed for response or no response to BAT. Patients with PSA declines of greater than 50% from baseline after 2 or more doses of testosterone were considered to be responders. Whereas, Non-responders had no PSA decline after 2 doses of testosterone and subsequently manifest a PSA increase of >50%. Differences between these two groups of patients were analyzed using clinical and laboratory parameters. All patients underwent genomic testing using circulating tumor DNA (ctDNA) and germline testing pre-BAT.

Results: Twenty five patients were non-responders and 16 were responders. Baseline characteristics between non-responders and responders varied. Responders were more likely to have had a radical prostatectomy as definitive therapy and were more likely to have been treated with an androgen receptor (AR) antagonist (enzalutamide or apalutamide) immediately prior to BAT (compared to abiraterone). Duration of prior enzalutamide therapy was longer in responders. Non-responders were more likely to have bone-only metastases and responders were more likely to have nodal metastases. Assays detected ctDNA AR amplifications more often in responding patients. Responders trended toward having the presence of more TP53 mutations at baseline.

Conclusions: BAT responders are distinct from non-responders in several ways however each of these distinctions are imperfect. Patterns of metastatic disease, prior therapies, duration of prior therapies, and genomics each contribute to an understanding of patients that will or will not respond. Additional studies are needed to refine the parameters that clinicians can utilize prior to choosing among the numerous treatment alternatives available for CRPC patients. This article is protected by copyright. All rights reserved.

Keywords: BAT; CRPC; Testosterone; ctDNA; prostate cancer.

This article is protected by copyright. All rights reserved.

[Ramp7]

I've completed one BAT cycle. PSA reduced by about 50%. I am Chemo naive, and just completed a Trial Study with LuPSMA177 at Dana Farber with some degree of success. PSA initially dramatically down 8.1 to 0.19. But slowly rising. I have one nodal met and one bone met. Presently on the low side of my second cycle. PSA and T shall be checked this week.

[Ramp7 in reply to Ramp7]

Just got my latest PSA 1.53. This is excellent news. During the high phase of this BAT cycle my PSA was 4.08. Responding well.

[ragnar2020 in reply to Ramp7]

Mark,

Good for you. Nice news. Hope your discomfort has been reduced and you’re moving around better.

Jeff

[cesces]

Not very definitive it would seem.

Not after all these years.

[cesces]

Sartor is speaking at the May 6th Cancer ANCs conference in Jersey City / New York.

If anyone attends would they ask him about bat and why anyone, under what circumstances, should choose it as a therapy.

I'm certain he will have a good answer.

[CurrentSEO]

looks like mother ship treatment (preferably by surgery) or maybe radiation is important for BAT success. It seems logical as given testosterone to mother ship without any definitive treatments to it is risky to say the least.

Also on this site most of the successful modified individual BAT programs … looks like all the success stories had previous definitive treatment to the prostate… or maybe I missed someone who still has an untreated prostate and successfully using BAT? I would be interested to know.

Maybe for oligometastatic also prudent to do external radiation to the spots before initiating BAT? Atleast it is my approach and understanding.

Surgery is not an option for me, will see if I can do radiation to it before starting my modified BAT.

[Hidden in reply to CurrentSEO]

I have started BAT, two cycles and PSA is steady at 2. Intact prostate, previously radiated. PSMA and FDG scan both negative 6 weeks ago. Two reasons for BAT, first it sensitizes for a rechallenge with Enza, PFS2 around a year gained. Second and equally important, immune theraphy works better afterwards. 4 out of six had a 50% drop in PSA using Pembro. BAT and then Enza seems to prime by upgrading PD-L1. I also have a biallelic BRCA2 mutation + vus for ATM, the cells are vulnerable being HRD. Extreme response?

Doc.: ncbi.nlm.nih.gov/pmc/articl...

[CurrentSEO in reply to Hidden]

Hi, thanks. Great to hear that you doing good on BAT with external radiation treated prostate and interesting info regrading upgrading PD-L1 (as mine is currently not over-expressed and no targetable mutations whatsoever).

I will be starting modified individually tailored BAT in August (still working on design as I have time till August), doing now ADT, 7 months lead on by Orgovyx.

I have both FDG+ And PSMA+ avid cancer with doubling time of 3.5 weeks if doing nothing.

This month finished SBRT to right femur lesion (in between to Lu-177 infusions) ... now looking to externally radiate prostate... as I had suspicious bladder neck invasion and possible rectum fascia attachment to prostate (so spacer maybe difficult if possible at all). I hope orgovyx and finasteride plus Lu-infusions shrink prostate and kill all PSMA avid cancer plus some FDG+ "neighbors". That is in total 5 Lu infusions so far, 3 one year ago and two this year, each time 4 weeks apart in Austria.

Irradiation of prostate seems important (if surgery out of the question) prior to BAT and I'm looking for Carbon Ion in Heidelberg as it looks like as a best option to spare healthy tissue.

If you don't mind please answer few questions:

Are you doing standard 1 month BAT with cypionate 400mg once a month? If not what is your protocol?

Are you using any other meds for BAT (finasteride, dutasred, etc..) that are not in standard BAT protocol?

What is you testosterone level prior to next cypionate (?) injection?

Do you measure pick of your testosterone level? If yes what is it?

Do you control your estradiol level?

[Hidden in reply to CurrentSEO]

I am on a std protocole, T Cypionat each month - using Zoladex, nothing else. T will be checked next time, 17th of April. No, estradiol level is not checked, I can Ask the MO next time I visit

[CurrentSEO in reply to Hidden]

Thanks

[Hidden]

There is a FB group specializing in BAT, lots of important info.

[CurrentSEO in reply to Hidden]

Please share the link or here or by private message. Thanks!

[CurrentSEO]

Thank you! I joined FB group. I don't give Facebook my personal data, I registered there as Current SEO as well 😀

Never was a facebook guy, but now have to learn more how it works.

It is indeed sad that members being pushed out... maybe some of you regulars in this forum can apply to HealthUnlocked to become Admin/s of "Fight Prostate Cancer "or setup a new forum and administer it from scratch and maybe even make it by invitation private group?

I would prefer "Beat Prostate Cancer" or "Control Prostate Cancer" or "Experimental Ways to Control Prostate Cancer"😜 name, then "fight" it however - as if you are asking for the fight... fight you are getting... but that is another topic.

Thank you again and best of luck designing yours BAT and keeping PC under full control and as well!

We keep in touch👍