BAT Question

[NDJIM]

I just read something on the internet that a new study shows that after ADT stops working injecting high levels of testosterone seems to hold progression back for a period of time. Does this sound true or a bunch of internet hocus pocus? It goes against most everything that my Oncologist has told me. Thanks everyone in advance.

[Derf4223]

Can you provide a link to that study? Here's one back at you

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

If you don't want to read it, it says there is little data about giving it to patients with advanced PCa.

[dhccpa in reply to Derf4223]

Was that BAT, or just stopping ADT and adding Testosterone?

[Justfor_]

This isn't BAT, but there was someone here that used supraphysiologic T to maintain low PSA. He had not failed ADT, but instead stopped it after few months due to unbearable SE. The majority of BAT users frequent "Fight prostate cancer" forum where there is no SoC policing like here.

[Tall_Allen]

So far, it has not proven to delay progression, but it has allowed for longer benefit of Xtandi (but not Zytiga). It may help some patients but makes the cancer worse in some patients too. The amount and patency of androgen receptors on the cell surface may make the difference. They can test for that at Johns Hopkins. It is potentially dangerous and should not be done outside of a clinical trial. Here are the findings so far:

prostatecancer.news/2016/09...

[Don_1213 in reply to Tall_Allen]

Allen - I believe the latest update to the page you referenced was in 2020? The link I posted (in Nature) is the results of a study concluded in 2024. It has additional information the reinforces the use of BAT - or I believe in this case - long term TRT raising T to a quite high level for extended periods of time.

I'd really look forward to your comments on that paper.. nature.com/articles/s41467-... - it's quite data dense, more than I'd be comfortable with coming to a conclusion with, but perhaps you might understand the data much better than I can.

[Tall_Allen in reply to Don_1213]

I ignore any non-clinical data, and suggest you should as well. Researchers do mouse and other in vitro lab studies to generate hypotheses to test in future clinical (human) studies. We can be pretty sure that most of what is true in vitro or for mice is not true for humans.

My review article is up-to-date in all clinical trials on BAT through June 2024.

The closest clinical trial to what interests you is the trial at Johns Hopkins and reported October 2022. It found:

• High androgen receptor (AR) activity is required for BAT to work. Only about ⅓ of CRPC men have high AR activity.

• But AR inhibition first is needed for T to raise its activity

• High AR activity downregulates c-MYC.

• High doses of testosterone (T) increases AR activity.

• Xtandi (but not Zytiga or other advanced antiandrogens) prevents acquired resistance to T because it upregulates the AR while it inhibits it.

jci.org/articles/view/16239...

So AR activity (requiring tumor biopsy) may be a valuable biomarker, and it is certainly dangerous to attempt BAT without monitoring AR activity. JH has a proprietary test of AR activity that everyone on any of their clinical trials gets.

Maybe someone will develop a biomarker test for AR dimers vs monomers as a result of the Duke study and test it in a clinical trial.

[Don_1213]

I commented about this in another post - the link to the paper is: nature.com/articles/s41467-... and it basically validates BAT for men who have advanced cancer. It's a VERY interesting study (the study is really dense - TA will have to evaluate it) - but the conculusions are understandable and IMHO - valuable.

[Justfor_ in reply to Don_1213]

Many-many thanks for posting this link. First off, because the references (11) and (12) mentioned therein are the direct answer to the OP's query. But more than that, because it lays down a theoretical basis to my (empirical) adaptive Bicalutamide scheme.

[Don_1213 in reply to Justfor_]

I just took a look at references 11 and 12 - and they appear to reinforce the use of BAT from what I could see (I don't have the subscription $$ needed for article 12.. but I could read the summary of it.)

[Justfor_ in reply to Don_1213]

The OP wrote BAT on the subject but wanted to know whether continuous high T can stop progression. The two references, pre dating recent paper, confirm this but for a limited time. This weakness of supraphysiological T comes BAT to remedy. It is worth noting that the original BAT period was one month, but users like Mateobeach have extended it to three months, not to mention Patrick's irregular periodicity that, if memory serves, could extend to circa a year. Bottom line: This new paper tried to shed light to a well known "paradox". Paradox in quotation marks because as a popular Greek expression has it: "Is the shore line crooked or are we sailing wrongly?". It seems that the latter is more probable. (Είναι ο γυαλός στραβός, ή στραβά αρμενιζουμε

[j-o-h-n in reply to Justfor_]

I always though paradox meant two Greek Doctors....Yiasou Patrioti.....

Good Luck, Good and Good Humor.

j-o-h-n

[MateoBeach in reply to j-o-h-n]

Yeah, John. Good one. You’ve still got it!

[MateoBeach in reply to Justfor_]

Yes, I have been on long-cycle BAT for over two and a half years now and am still maintaining undetectable PSA <0.015. Note that I am still hormone sensitive (mHSPC). My MO this week, who prescribed my T-cypionate and Orgovyx and Nubeqa, suggested that the cycling of androgen receptors activity may be preventing progression to castrate resistance.

This article further clarifies aspects of the Mechanisms for its efficacy. Cycling high levels of exogenous testosterone with periods of very low castrate levels through ADT meds and ARSI such as Nubeqa is essential for it to continue to be effective. Any treatment regimen that is continued indefinitely will inevitably fail as the cancer evolves for it. That is why BAT. Probably. A work much longer than continuous high testosterone TRT.

My own regimen includes high testosterone of three months alternating with one month of no testosterone and ADT with Orgovyx and AR blockade from Nubeqa. Continuous Lupron is not necessary with this as it does nothing during the high-T cycles. The low T cycles allow a reset of AR number and expression to a high level along with c-MYC expression. MateoBeach

[muttonman in reply to MateoBeach]

Great study on yourself my friend, I'm in your corner on this!

[cfhny in reply to muttonman]

I believe there may be a lot of us in MB's corner!

[EdBar]

My oncologist, Dr. Sartor at Mayo has a number of patients that are using this therapy with good results. You still receive regular Lupron injections but stop using Enzi or Abi. High dose testosterone is administered which boosts your levels and then they fall back until the next T boost. He has patients able to control their progression with great success for extended periods all the while boosting QOL. Eventually it will cease working and Enzi is restarted and often becomes effective again. The theory behind it is that cancer cells that have adapted to a low T environment are overwhelmed by the sudden boost of T. Dr. Denmeade at John’s Hopkins is another top oncologist familiar with the treatment. Lots of trial information you can look up - RESTORE trial COMBAT II trial.

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

Ed

[fast_eddie]

Good luck finding a urologist or MO eager to prescribe BAT treatment. I've mentioned it to two urologists and they both consider it 'fringe' therapy regardless of any positive studies, which they likely have no interest in reading.