Here's a treat - a review of BAT (Bipolar Androgen Therapy), actually written by Dr. Sam Denmeade [1].
In his intro, he makes a point of stressing that androgen receptor axis therapies are "highly effective palliative therapy, but they are not curative." A few years ago it was reported that an extraordinary percentage of men on ADT etc, hold the belief that there is a chance of a cure. I don't believe that magical thinking is helpful. Knowing that a therapy will fail is motivation to develop Plan B.
Denmeade introduces a much-needed new term: "complete androgen inhibition-resistant PCa". "However, the majority of PCas remain addicted to signaling through AR throughout the course of the disease." "Studies dating back nearly 30 years indicate that high expression of AR induced by prolonged castration becomes a vulnerability of CRPC cells in vitro and in mouse xenografts to supraphysiologic androgen (SPA), which induces cell death and growth arrest in this context."
Regarding BAT: "This rapid cycling is intended to disrupt the adaptive of AR regulation associated with chronic exposure to high or low levels of testosterone"
IMO, the disruption of adaptation is best started at the inception of AR-axis inhibition therapy, with the first testosterone boost occuring after 3 months, or so.
"Conclusions/Recommendations
"Our cumulative clinical experience over the past 10 years treating >250 CRPC patients establishes the meaningful clinical activity and safety of BAT and supports additional studies to determine its optimal clinical integration. Key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with mCRPC; (b) does not produce symptomatic disease progression; (c) produces sustained PSA and objective responses in 30%-40% of patients; and (d) can re-sensitize and prolong response to subsequent antiandrogen therapy.34,36-40 While ADT for advanced PCa often produces debilitating sexual and metabolic side effects, another highly significant feature of this approach is that BAT can make men feel remarkably better by decreasing fatigue, increasing physical activity, and restoring libido and sexual function. BAT can also increase skeletal muscle tone and decrease visceral and subcutaneous fat.48 Thus, the incorporation of inexpensive, high-dose testosterone via BAT into the treatment paradigm for men with CRPC has the potential to improve quality of life (QoL) and minimize morbidity from the metabolic sequelae produced by androgen ablative therapies. Patients who are interested in more information on BAT can be referred to a recent review written for a lay audience.48
"Ongoing clinical trials are designed to assess the optimal way to sequence and combine BAT in PCa. Patients are encouraged to seek out and participate in such clinical trials when possible. For those without access to trials, there are 2 clinical settings in which BAT could be recommended based on the available clinical data. First, for asymptomatic patients who have initially progressed on ADT, BAT could be administered prior to starting an ARSI due to its marked ability to enhance subsequent response to these agents. Second, in men with CRPC progressing on abiraterone, BAT can be considered as part of sequential therapy with an antiandrogen based on results from the TRANSFORMER study. Importantly, BAT should always be given in conjunction with ongoing ADT. BAT is not to be used in patients with castration-sensitive disease outside of a clinical trial. BAT is also not currently recommended for use in patients with PCa bone pain as these patients are at risk for significant worsening of pain following testosterone injection. In those few patients who experienced pain flares in BAT clinical studies, we have observed that the flare usually occurs within 12-48 h post-testosterone injection. Pain can be treated with anti-inflammatory medications but may be severe enough to require narcotics. It typically resolves after ~1-week post-BAT, when the testosterone level begins to fall. For those patients who do develop a pain flare on the first dose of BAT that resolves by the end of a 28-day cycle, consideration can be given to continue BAT for a second cycle. We have observed pain improvement or resolution that did not return with subsequent cycles of BAT. For those patients who continue to have pain at the end of the first 28-day cycle, BAT should be discontinued."
Denmeade doesn't appear to be in a hurry to address the needs of men with castrate-sensitive PCa. I jumped the gun 18 years ago & remain castrate-sensitive. PCa is easier to manage if CRPC & complete androgen inhibition-resistant PCa can be avoided.
There is no evidence to support NOT using BAT (or its variations) in HSPC. In fact it may work even better and possible delay or prevent progression to CRPC. It has not been tested formally (clinical trial) one way or the other. It is just an untested theory that it would not be beneficial just because the original BAT trials were limited to mCRPC.
But for those of us, including me, who are using it with the support of our MOs, provide anecdotal examples that it can and does work. (My PSA is down 90% to 0.03 after two years on long-cycle BAT and remain HSPC.)
It is time for a clinical trial of BAT in mHSPC. And yes, perhaps even before starting an antiandrogen. BTW, the continuous ADT does absolutely nothing during the phase of BAT with high exogenous testosterone. That is why I only use Orgovyx for my one month out of 4 at castrate levels for "reset". I hasten to note that my regimen is not SOC.
I am a relative newbie to BAT. Per my discussion with Denmeade he thought Lupron in the background would work along with High/Low T. I am using Propionate and you are using Cypionate. Using Orgovyx may be worth considering at some point. My Testosterone was just checked at the Low side of the cycle, (7).
Welcome to the BAT Pioneers Ramp7. You have been through the full meal plan for PC since 2008. I see you responded fairly well to 6 Pluvicto infusions for mCRPC but then relapsed. And now in to a BAT protocol with the support of Denmeade (you meet his criteria) and your own MOs. And I see that you showed a favorable response with significant PSA drop with your first cycle (rather than a significant rise). Congratulations on that! So now how far and for how long can you (or I) extend it.
The original BAT trials were just proof of concept and were not optimized. Once monthly 400mg T-cypionate gives only a brief window of SPT levels (>1500-2000), perhaps a week. And then drops low as it slowly clears, but does not get to castrate level at all before the next cycle, despite the Lupron. That is sufficient to assess favorable response but is probably not optimized. (My own, non SOC, regimen is detailed in other posts. Consists of 3 months maintaining SPT, then one month castrate on Orgovyx.) Others are also testing longer cycle BAT in clinical trials and per individual protocols. One challenge is providing sufficient time for T-cyp to clear ( 4-5 weeks) to enter the castrate phase. Your use of T-propionate with its much shorter half life should permit (solve) that within one week. But must also be injected frequently throughout your chosen high-T phase. I think you have chosen a reasonable approach and initial results are encouraging. I wish you well. You can PM me if any aspect you would like to discuss.
I remind anyone reading and considering this or similar that it is not SOC even though we are doing it with the support and monitoring of our MOs. There are serious known and unknown risks that we have explicitly chosen to accept. Paul /MB
The length of High T cycle and rate of decay are of particular interest to me. Your long High T time period intrigues me from an effectiveness point of view and also QOL.
My old regimen, which was good for over ten years, was 3 months of T at ~1,000 ng/dL followed by 3 months castrate. QoL was great. Most of the time I used AndroDerm daily patches - until Insurance clamped down on T prescriptions. So I switched to T-cyp, which was cheap enough that I wouldn't have to rely on insurance.
PSA went quite low, but ~35 after 3 months of T. Very short PSADT.
So I gave pure BAT a shot. That was a disaster.
I'm on a 3-month cycle with a single T-cyp injection, but I'm wondering if a second injection a week later might be more effective? Or a solid month of high T? etc.
I found that saturating testosterone to clearly perceived status was slow when coming off castrate. I’ve started adding a second shot within 4 days to a week of the first to accelerate the process. Then 400mg every two weeks. 4 weeks before transition to castrate month is the last shot so it can clear. And I use testosterone gel (inexpensive Mexican brand OTC here) for the last two+ weeks. 100mg / day topical. Then one week on no T; then start Orgovyx for a month. Recently added half-dose darolutamide for just the first week on Orgovyx to make a sharper AR deprivation, blocking any remaining T. One month hopefully might be enough to cause AR amplification and disadvantage AR+ sub population. No data to support this though. Ready to further modify if /when it shows signs of failure.
I live six months a year in Los Cabos area of Baja. My MO in Oregon does prescribe me testosterone for my regimen. But while down here I can re supply because testosterone, both topical and injection are available and inexpensive without prescription in any pharmacy. The topical gel most available is called LoTyel.
MateoBeach wrote --- " ... (My PSA is down 90% to 0.03 after two years on long-cycle BAT and remain HSPC.) ... "
AND ALSO
" ... Welcome to the BAT Pioneers Ramp7... "
I've been on/off/on/off/ -- etc. my Cypionate Injections for 7+ years after GL10 was treated and wondering if I meet the stringent MEMBERSHIP requirements? 🤔 😀
Three months on BAT, then 6 weeks with Enza, PSA from 7.3 to 0,14 - amazing after 45 months diagnosed with all the bad stuff G9, IDC, PNI. My Norwegian MD is amazed, should not be possible.
Another success story with BAT. Congratulations. You should consider our outside group of prostate cancer hackers. We are compiling a series of responses to individualized BAT programs. Sharing results and ideas. PM me and I can give you a link. Paul
Good discourse pickup after the loss (to FPC/HU) of Mr Prolific, smurtaw/Russ. For those of us waiting in the wings to try BAT (hs or cr flavor), we are continually indebted to the information-sharing that you BAT pioneers provide. A generous Hat-Tip (Jarabe Tapatío for you, MB) to one and all - as you likely are showing the way for future SOC.
Thanks for the share Patrick and to those who commented. I’ve was successfully on Xtandi/Avodart/Finesteride for 9 years and it looks like it’s finally failed. Not sure of my status as to HSPC or CRPC. I’ve been looking at BAT as an option and reveling in the possibility of a QOL upgrade. 9 years of chronic and debilitating fatigue is enough. PSMA scan and meeting with MO in a couple weeks.
Since 2017, I've had 3 T levels done - 667, 737, 726. Doesn't appear DHT levels were checked. There was also one Free T 8.71 which was done at the same time as the 726 back in early 2019. 😀
That was a good run Brian. A few cycles of even standard BAT might restore responsiveness to AR blockade. But would try to switch over to Nubeqa if you can. When on BAT it is probably counterproductive to use the 5ARIs as high DHT may actually be part of the mechanism of SPT inhibiting PC.
Thank you MB, I will add Nubeqa to my discussion list for my meeting with the MO.
We were going to go the Pluvicto route and I had a consult with a RO here in NM who was part of the VISION Trial. Unfortunately my consult was about 2 days after Novartis stopped accepting new patients until they square away their QC/Supply issue. 🙁
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Time to impeach for prostate cancer
ADT vacation versus Continuous
brca-2 advanced prostate cancer
Intimacy during Prostate cancer treatment 
Where do I go for alternative to continuous ADT?
