It worries me that some patients seem to be looking a BAT through rose-colored glasses, and pressuring their doctors to do it off-trial. I've been following BAT since its inception, and even donated money when it lost NIH funding. I am still hoping that they will be able to pre-identify patients who will respond to it vs those who get worse because of it. So far, there is no evidence that it extends survival, and may make matters worse. It should only be done in carefully watched clinical trials now ongoing at Johns Hopkins, UW Seattle, and UC Denver.
Let's review:
•Schweitzer et al. found that half the patients did not respond at all, and PSA continued to rise
• Markowski et al. reported that using a PSMA PET scan (DCFPyL) 3 months into BAT treatment revealed that half of them had already progressed to having new metastases.
• Sena et al. reported that in Arm C of the RESTORE trial (ADT only),
- PSA more than doubled in 52%, and increased markedly in 14% more.
- Only 14% had a reduction in their metastases. All of those had lymph node metastases only.
- Musculoskeletal pain was experienced by 40%. Other prevalent side effects were: hypertension (21%), breast tenderness (21%), leg swelling (17%), fatigue (14%), and difficulty breathing (10%). One patient died of a stroke.
- There weren't any discernable genomic determinants of response.
- There was no statistically significant difference in overall survival between those who went from Zytiga -> BAT -> Xtandi and those who went from Zytiga -> Xtandi
- Comparing BAT to Xtandi (before crossover), there were no significant differences in the time to clinical or radiographic progression (5.7 months in both groups) or reduction in PSA by ≥ 50% "PSA50" (28% and 25%)
I am sorry, I can’t comment on this topic because I have no knowledge about it but I just can’t thank you enough for looking out for us and doing all this research. You are really a great asset to this platform. Thanks again.
1. Nice comment. It makes a lot of sense. BAT needs to be treated with respect.
2. What if you want to consider it as an option, and you try it for a few months. Will, it not quickly become obvious if it is you are one of the few people for whom it is going to work.... or not?
The side effects of the alternative treatments are no great prize, are they.
I know when I tried some DHEA sublingual my PSA doubled quickly. Can't prove why or that it was related to the DHEA but it sure was coincidental
As castrate resistance sets in, the androgen receptor "learns" how to use other ligands (like DHEA) to be activated. Also, AR expression increases so that activation occurs with even the slightest amount of testosterone.
Well this was before I was even taking ADT-I only started a week and a half ago. But the concept would be the same. the receptor uses what's available. my T at the time was in the 280-320 range. which is what it was before i started taking Androgel from 2009-2016, and what it returned to after I quit. But I would conclude from that trial of one that BAT probably would cause an uptick in cancer for me.
Glutaminase activity may be a factor in increasing mitochondrial glutamate which supports tumor growth. The AR is an important stimulator of glutaminase activity. But, at some point glutaminase activity becomes independent of AR and supports progression to CR independent of androgens. Compound CB839, a glutamine transfer inhibitor which blocks transport of glutamine into mitochondria is undergoing clinical trials in many different trials. Results from trials with prostate cancer has been limited to cell lines.
Thank you for that. I am also following it closely, but more as a last resort when nothing else seems to be working. I suspect, by then, it will be too late, but hopefully it will be far enough into the future that the powers-that-be might have refined it so it is more promising.
I did 6 months of estrogen-based ADT and followed it by 17 months and counting of high testosterone (between 2100 to >3000 ng/dl). I've blasted through the predictions (3 months - I've gone almost 2 and a half years now).
But I might be a hyper responder. Faced with the risk or a long bout of ADT I chose to roll the dice - my reasoning was 3 months of life with testosterone beats 30 years with zero T (for me, not for everyone, some don't mind zero T. If you knew me and my interests you'd know it severely hinders 99% of what I enjoy).
My point is that while it might seem simple to "know" what is right for others, it doesn't always work that way. We are a heterogeneous bunch.
I'm still reveling in 2 years of added life. And life with the glory of testosterone and all that it brings to the table (again, MY opinion only).
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That sounds like a good result. I was looking through your posts and profile but couldn't find your treatment history. Could you share that with us?
It left me a bit confused though. Your treatment history says you were diagnosed in 8/2019 and had an RP in 12/2019, but then you talk about 6 plus 17 months of various treatments and you said: "I've blasted through the predictions (3 months - I've gone almost 2 and a half years now)". I was wondering how you get 2-1/2 years from an 8/2019 diagnosis and 12/2019 start of treatment. Also wondering if a doctor said you had 3 months or where that came from.
I agree very much that we all must do careful research and risk analysis before making any decision on BAT. That goes for every new treatment for all of us at our stage. All options are risky. So to our readers: understand yourself and find a doc who also understands. Follow the science as best you can, have a team and regard them as colleagues in the fight of your life.
However… there has been a massive over estimation of the risks of testosterone. The myth that T fuels cancer is still in text books. Aspects of this scientific fraud have been extensively discussed on other posts so I will not bore you here.
Your post here is an iteration of views you gave on another post. Thanks for bringing it to wider attention, these are important issues. I responded and below I have posted it in quotes but essentially I think you too are over emphasising the risks of a simple and cheap clinical procedure to manage and extend the usefulness of some of our most important anti androgens. Yes much more work needs to be done but I do not want to die waiting. That too is the risk we face.
“The transformer trial showed that BAT alone (with continuing ADT) was as good as and maybe even slightly superior to enza after failure of abi. That is itself a major conclusion applicable to clinical practice. (ie BAT is the equal of the 2nd generation lutamide in effectiveness) The 2nd conclusion was even more relevant and something that many of the earlier trials did not address (perhaps explaining the appearance that BAT may not be so effective. ) That is, the resensitization of lutamide-like anti androgens or making them more effective in the first place.
There are 2 different things happening with BAT. First there is the primary effect of the BAT. In my case it was a reduction of PSA by about 30% lasting about 8 months. (disappointing in my view) The second effect becomes apparent when rechallenging with a previously failed lutamide (in my case bical but also shown for failed enza). In my case a PSA drop of 80% for a bit over a year. (this was a pleasant surprise) While I found that repeating the whole exercise became more and more difficult with each iteration. However at the end of it all it gave me 3-4 years more of bical even after it initially failed. That is 3-4 years that I would not have had otherwise. This was confirmed by radiological means (Ga PSMA). In the Transformer case it was that the crossover sequence BAT to enza was far superior to the sequence Enza to BAT and BAT seemed to sensitise the cancer to Enza. (All this after failure of Abi.) ( addendum: I would have been very interested in the result if they had taken the enza to BAT group to a rechallenge so that it went enza to BAT to enza again.) Conclusion: even after BAT fails it is worth rechallenging with the previously failed lutamide and when starting enza for the 1st time it is worthwhile doing a sequence of BAT (perhaps 3 months) before starting enza. (note it does not work so well with abi)
We do not know exactly the circumstances in which BAT is most effective but we do know that it is a fairly safe (and easy and cheap) clinical practice and many of the earlier trials did comment that it was a relatively safe procedure. Safe is of course a relative term here because ANY treatment at our stage carries significant risks that each of us must evaluate.
So, even looking at some of the earlier trials (sometimes which did not factor in the resensitization effect) there is a clear conclusion that done properly, with good monitoring and expert advice, that BAT is a safe clinical option in the right circumstances. For sure, more research needed to focus down on its best use. The same can be said for all treatments at our stage.
We can also learn much from the body building community, many of whom use continually supra levels of T up to 10 times that used in BAT. They show that careful monitoring and management of effects (eg judicious use of Arimidex) make it feasible and sustainable. Body builders do not appear to have any issues with PCa.”
It is not a "myth" that T fuels prostate cancer. What do you suppose an androgen receptor is?
I'm glad BAT worked for you, it works for about half of men. You were lucky.
There is NOTHING to reinforce that statement that bodybuilders do not suffer from PC. I'd love to see evidence for that. I've personally known several.
It is NOT always safe, many men who had progression to symptomatic painful metastases while on BAT. Wishful thinking on your part do not make a thing true - only the facts do. Take off your rose-colored glasses and look at the evidence I posted - that is all there is.
Great use of sarcasm! Really adds to your arguments.
Fact: some of us do great on BAT or SPT and case studies and clinical trials come to the same conclusion (as far as I know, the researchers aren't wearing rose-colored glasses while they write their reports and neither am I as I type this). Others don't fare as well.
And I have yet to understand why I need a doctor to put me in a clinical trial. One of my current doctors has stated several times that I know more about my particular cancer than he does. My other doctor tried to talk me out of estrogen ADT. Then she saw my labs - consistently undetectable T. She quickly changed her attitude and has been a confidant who offers information (kudos to her - it takes a big person to admit that they don't know everything and has the ability to change). She now simply tells me to "keep doing what you're doing because it's working". My prior doctors were dead wrong in their opinions of my future.
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Do you have distant metastases?
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Not as of 09/2020. And my MO thinks I'm clean. I had the scans done in preparation for radiation. But she later talked me out of it.
We have known since the early 2000s. Read Morgenthaler. Many indications before that. As regards body builders I have searched the effects and side effects of supra T. Not a hint of Pca. Indeed there is a suspicion it may be protective.
I have read Morgentaler, and you misunderstand him completely. He never said that testosterone doesn't activate the AR. He only said that for non-metastatic men, the ARs are saturated when T is at low levels (about 100-150 ng/dl). When there are metastases and the AR is overexpressed, none of that any longer applies.
Your anecdotal evidence on bodybuilders proves how much you have succumbed to your confirmation bias. It is dangerous. There are several bodybuilders on this site. In addition, here are some contrary anecdotes:
Yes, anecdotes only. No systematic evidence. That in itself is significant since on the T is fuel hypothesis we would expect many many more cases. Modus tollens.
Interesting that usually TA states that without RCTs anything is meaningless. Yet now he cites mathematical hypotheses and case studies. A great example of confirmation bias or cognitive dissonance.
An Excerpt from the "Good News Network" link you posted.
"After surgery to remove his cancerous prostate in 1998, he took up bodybuilding in a bid to “come back stronger” and transformed his physique with a strict healthy eating regime and committed to three gym sessions a week."
Denton Wilson started bodybuilding --after-- his prostatectomy. The "strict healthy eating regimen"?
Denton Wilson is a "natty". "Nattys" go through rigorous testing. A link with some info.
Mar 17, 2016 · I’m Denton Wilson. I am over 60 years old. I am a natural bodybuilder, currently number one in Britain for the over 60s Masters. I am also a personal trainer. I’m passionate about health and
The IFBB pros that compete in the Mr. Olympia and The Arnold contests are the bodybuilders that take roids, T, insulin and other things to work around their natural peak levels of musculature. They also have doctors that closely monitor their health while they are on their drug cycles.
Those are the men and women that might have a higher incidence of cancers, but really, they take so many different roids and drugs how could anyone attribute a higher incidence of cancers among them to only testosterone?
Denton Wilson is "clean". When I read the article you posted about Wilson, it seems highly likely that his prostate cancer is hereditary. After meeting his estranged father that died weeks later from prostate cancer Wilson decided to be tested. He wasn't a bodybuilder at that time, natty or otherwise.
If anything, working out will raise one's T. Especially the big, multi-joint exercises such as the back squat, deadlift, power cleans and overhead presses.
I lifted for athleticism at one time. I had the natural genetics for size, proportion and symmetry that some take drugs for. I was going to be open a personal training studio, one on one. After telling my uro that I had been diagnosed by my chiropractor as having an adverse reaction to the fluoros commonly used--he continued using them--and he likes to prescribe Cipro orally and just before a procedure, the large, intramuscular, shot of Levaquin. I have about $30,000 of weights and equipment and could hardly get out of bed let alone finish putting the gym together. I own a large house.
About me--doesn't matter. I never--never did a roid or T --or insulin. My health was my wealth. Someone that has been making a blended drink using organic seeds and nuts and so on isn't likely to take a drug.
Denton Wilson is a "natty"! These guys are tested to the max when they compete at the level he did or still does. Again, from the link you posted about him,
""After surgery to remove his cancerous prostate in 1998, he took up bodybuilding in a bid to “come back stronger” and transformed his physique with a strict healthy eating regime and committed to three gym sessions a week."
If Denton Wilson hadn't renewed his relationship with his father he would not have been tested. His father had prostate cancer. It is very likely hereditary in Wilson's case. It isn't about me or what I did. I understand that this is an area that you have limited knowledge about. These men and women that use these drugs to build muscle take so much and so many different drugs that that can't be used as an example of what supplementing with T can do. Usually when bodybuilders have "gear" related health problems their hearts give out or there are liver or kidney tumors.
Some of the pros that compete in the Olympia and The Arnold or are working towards it die from this crap, the "gear" they put into their bodies.
As for competing in these contests, the pre contest dieting is unhealthy. I intended to do it once simply because the trophy can greatly increase the money certain clientele will be willing to pay to be trained. Things changed for me. I went years sleeping for an hour or so max before the pain from the fluoroquinolone damage woke me forcing me to find a different position.
If the question you posed, "Aren't you a bodybuilder with advanced PC?" was asked because you thought I had perhaps used "gear" or even ate crap, maybe? Well sometimes dirty protein and a portion of pastry are life's pleasures. Not often.
Lifting, athletic endeavors and the like don't cause prostate cancer.
You did post some interesting links and started a spirited discussion--that's for sure! 93 replies as of now! Much info was posted and queries made. You warmed up the keyboards with this T_A!
Exactly. If it were true that "T is fuel for cancer" Then body builders taking the amounts of T they do, should be dropping like flies from PCa. Not just a few. Most of them. They are not.
That is a form of reasoning called Modus Tollens. It has the form "if a then b. But we find not b. Therefore, with certainty we can say not-a". This is true in all possible universes.
The fact is, too little T puts men at risk of PCa. You cannot believe both the "fuel for cancer" nonsense and any form of the "saturation Theory".
As you saw in my post, supraphysiologic doses of T have vastly different effects in different mCRPC men. There is no evidence it increases survival in anyone. No one knows how to predict responders.
kaptank...The observation by you that Lutamide efficacy can be prolonged by having T in the system is worth exploring. This is likely to be true.Resetting your T...tends to reset the normal physiology and possibly makes a lutamide to become effective again.
I do not have experience with BAT but have been doing intermittent Bicalutamide mono therapy ...where my T remains in 450-500 range with most of the good things which T brings to life. PSA still below 0.5 and ALP below 60. MRI clear.
We need to monitor our condition closely whenever we are using a non SOC or semi SOC treatment.
"no statistically significant difference in overall survival... no significant differences in the time to clinical or radiographic progression"
Some will then wonder, the TRANSFORMER trial shows what, exactly? Because you are not going to convince a certain subset of men to not consider BAT by telling them they can expect to live just as long on BAT with some risk but also with a potentially higher QoL. You might need to convince them that BAT has the kind of mortality/morbidity risks that were firmly established for treatments like high-dose DES, for example.
What you are also not mentioning in your argument is that some BAT trials consist partly (mostly?) of men rather far along in treatment or with very advanced/aggressive disease, and some of the discussion in the forum here seems to be about its potential for earlier use, before successive treatment failures. So you might also need to convince some men that trying it early, and bailing if it fails, poses serious risk. Is there evidence that it does?
The problem here is there is NO clinical trial evidence, pro or con, of early BAT use. So without that, men will end up looking at anecdotal, theoretical and mechanistic evidence.
I'm not saying its not worth reiterating that BAT falls outside the SOC, and for good reason. But as others have suggested, men should research ALL potential forms of treatment, whether SOC or not. And even a quick review of either TRT or BAT is going to bring up red flags right away. So I think virtually everyone here either trying or considering BAT already KNOWS they risk failure, pain and progression. Even without seeing solid evidence that it extends survival, statistically, some are willing to take that risk because they also do not see compelling evidence that it generally SHORTENS survival.
Yes, you can list side effects. But the SOC of ADT has side effects, too, and part of the appeal of BAT is the potential to mitigate some of those. I can understand the rationale of warning men that BAT is still an unproven, experimental and risky therapy. Perhaps along with that warning, though, it is worth suggesting that instead of pursuing BAT men might try to mitigate SEs of ADT with tE2 (either low-dose along with ADT or high-dose as a form of ADT).
Also consider what the definition of "to advocate" is, when you say that "it is incredibly irresponsible to advocate use of BAT..." I see a lot of discussion regarding BAT that fails to meet that definition. Someone who merely posts a journal article on BAT or posts details of his own n=1 experience is sharing information, not necessarily saying, "YOU should do THIS."
The fact is, some men are not going to wait (years? decades?) until we can pre-identify patients who will respond to BAT vs those who get worse because of it. They know they don't know, and they are going to find out the hard way, by virtue of choosing for themselves. Nobody is pushing them.
I never mentioned "symptomatic." I said far along in treatment failure and aggressive, meaning high Gleason and castrate resistant, having already been treated with ADT for multiple years and prone to multiple failures.
ADT usually fails in a couple of years. Men in the first trial you linked to appear to average over about five years of prior ADT. So the study could not have been on men considered early on in hormonal PC treatment. Another trial "required patients to have had progression on enzalutamide PSA rise after enzalutamide treatment discontinuation." So the point is, the testing of BAT is on men already experiencing serial failure of multiple meds.
You wrote that, "So far, there is no evidence that it extends survival, and may make matters worse." Some probably feel the evidence over the past seventy years of limited use of high-dose T might warrant extending that sentence to read, "So far, there is no evidence that it either shortens or extends survival for most men, and may either make matters worse or better for a given individual." Buyer beware.
Gleason no longer matters once one is metastatic. In the trials they have excluded very advanced cases - no bone pain, no chemo for mCRPC. In RESTORE, they allowed only one second-line hormonal agent. They were all castration-resistant, but contrary to your belief, they were not "far along in treatment" for it.
The question still remains as to whether forms of BAT can be used much earlier in the disease to arrest progression before a patient becomes castration resistant at all, let alone fails subsequent ADT attempts. Current trials do not answer that, so men will try to answer that for themselves.
”Gleason no longer matters once one is metastatic” - this is a question me and my father asked his doctor, since he is Gleason 9, and the doctors answer was ”Gleason always matter”. But my father said that he knows of 7’s with quick progression and 9’s with longer time to mets. Can you please elaborate on this so I can give it back to my father?
Gleason Grade does matter even if prostate cancer is metastatic. On this forum, some one has been spreading this myth that Gleason does not mater once PCa is metastatic. This is not accurate,'High Gleason means that the cancer cells are more mean and more distorted and hence more able to spread and cause problems at faster pace.
In other words, high gleason grade means the cancer cells are not well differentiated which means they are less like normal cells and are more aggressive.
Gleason score describes the cell architecture of the glands within the prostate. The higher the Gleason score, the higher the likelihood of metastases. But once there are metastases, it no longer matters. Metastases don't have a Gleason score. Metastases that can be more or less undifferentiated (i.e., more or less like prostate cells). That is where the focus lies after metastases have been discovered. In fact, in patients who are newly diagnosed with metastases, a prostate biopsy is completely unnecessary. The way they can tell how differentiated metastases are is by biopsy of metastases and IHC staining. But it is a moving target - cancer cells become increasingly less differentiated over time as genomic breakdown progresses.
Yes it has. Huggins himself tried supra T on patients on death's door as a hail mary pass. It didn't work and is the source of the falsehood that T fuels cancer.
There are at least 8 identified mechanisms for the effect of supra T on PCa. Only some of them involve androgen receptors. eg there are double strand DNA breaks. However what is now clear is that the relation between T and PCa is much more complex that the simple minded T is fuel for cancer. Let me emphasise what Morgenthaler concluded. THERE IS NO EVIDENCE FOR IT. It is an assumption and a line reasoning that goes "low T good therefore high T must be bad". That ain't so.
Spare the sarcasm? Without it, he would forgo half of his posts. On second thought, that would give him more time to look for case studies and mathematical proposals.On third thought, I find his comments entertaining and I would miss out on that.
Thank you. I am completely my own n=1 test cycle of T this week to see if I am a favorable responder for BAT. I am HSPC with only known PLN mets treated with RT and PSA low and steady at 0.08. So at a low risk state. I did 3 week doses of 200 mg TCypionate and now a 2 week washout (no ADT). Will check PSA response this week and report.
I think that is the time to take the risk vs. later. Worst comes to worst you switch gears, learn something, and move on. I learned that SPT doesn't seem to want to kill me. So I'll keep doing it.
I'll add my 2 cents. The main reason that I tried SPT (I guess sort of a strange BAT since I did a 6 month leadin of estrogen patch ADT and if my PSA ever breaches 0.1 or if I have a positive scan I'll do a short bout of zero T or radiation) is that I was willing to make a trade. A few months or maybe a year of testosterone against perhaps 3 - 20 years of ADT/chemo/radiation.
I don't know if I was just lucky but it has been 18 months on SPT with no evidence of cancer. My last scans were clean. My MO talks me out of doing any kind of SOC treatment. I hope she's right when she says I'm doing great and I don't need any treatments. I'm Gleason 9, T3b/c, lymph nodes, bladder wall, seminal vehicle, etc. Mayo docs gave me 3 months before painful return. That was in 2018. I saw them 4 months post surgery and they didn't know what to make of it.
Anyway, we all have different goals and sometimes those goals aren't aligned with zero T or chemo or even surgery or radiation (I did surgery and have no regrets but some would rather have a shorter life than mess with the sides and risks).
Rant: I have little tolerance for people who seem to think that they know what is best for someone else. I am me. Nobody else is. I don't pretend that I know what is best for them and I would like the same courtesy.
TA, you and I will once again have to agree to disagree. But before I take off my rose colored glasses and retire to bed, I'll just say that my husband's doctor is one of the esteemed ones from your list above doing clinical trials, and they are very pro-BAT for certain APC presentations. The clinical part of medicine (as in, seeing patients and confering with their MD peers and not just relying on trial data) is vital to understanding this disease, and we fully trust our docs in how they combine the art and science of medicine.
If he is doing a clinical trial, that is exactly what I'm saying - so we agree completely. It is through such trials that we may someday learn who benefits and who doesn't.
He is on 28 day cycles of 400 mg testosterone cypionate + ADT (in his case, orchiectomy). I appreciate your passion for reporting trial results, but here is why I struggle with your insistence on being in a trial: Clinical trials are not for the benefit of the patient but for the benefit of the research. The patient may benefit, but that isn't the primary goal. Trials have very strict protocols (which is another reason the results don't tell a full story, but I digress), and if a man does not fit the criteria, he doesn't get on the trial. It doesn't mean he won't benefit from the treatment, it just means that he doesn't check all the boxes. If the research is being done to find the best sequencing and the man has had treatments out of sequence with the study, he won't get in. Maybe he had a recent treatment, or maybe he's tried 2 or more advanced hormonals (Zytiga AND Xtandi for example), or some other exclusion. And trial start dates may be months in the future and men with advanced disease may not have the time to wait.
We would much rather be with a trusted doctor looking out for OUR interests than in a trial looking for a better understanding of the disease. Trials absolutely have a place in medicine, but they are rarely free, often require travel, and don't focus on individual interests. Earlier phases may even do real harm.
Circling back to BAT, my husband doesn't qualify for BAT trials but he is benefitting from the therapy. We are grateful for the opportunity to be outside the box and be with doctors who have been willing to try things (like 4 Zytiga with a full meal which allowed it to work longer) other docs aren't willing to try.
I have been in several clinical trials, and I completely agree with you. It is true clinical trials do not focus on individual interests.
One can get suboptimal clinical care when compared with personal physicians. I would rather have BAT with my oncologist than in a clinical trial. If I have negative side effects the treatment will be immediately stopped. This may not necessarily happen in a clinical trial and I do have experience in negative side effects during clinical trials.
One has to participate in clinical trials when there is not any other way to get the desired treatment.
Having been on several clinical trials, I disagree. In fact, one of the benefits when one is randomized to SOC is the quality of care one gets on the trial. But then I have been spoiled by the top investigators that it has been my good fortune to know. I have no doubt that the quality of care may have been lower in community practice. But that is true both within and outside of a clinical trial.
The nice thing about clinical trials is that there is IRB review, and very strict protocols. This protects the patient. Patients are required to be fully informed and to give informed consent. Patients are very closely monitored in a way that they ordinarily might not be. On many clinical trials, the lead investigator will allow patients to be treated "per protocol" who do not meet the strict inclusion criteria. They simply exclude those patients from the final analysis of results, protecting the integrity of the sample.
I've probably worked with many more MOs than most patients, but only at top hospitals. I would say that the majority are willing to "bend the rules" based on preliminary evidence. But they always make it clear that they are doing that and what the risks might be.
In theory, even with what is called castration resistance, there are some PC cells that haven't lost their androgen sensitivity. The surge of testosterone encourages them to thrive and predominate over the castration-resistant cells. At the same time it may reduce the over-expression of the AR. The idea is to create a dynamic balancing act. Let it go too long and the metastases will grow too big in size and number. Eventually a tipping point is reached and dynamic equilibrium can no longer be maintained. I suspect that the reason that they haven't been able to find predictive biomarkers is that there are none. It is the relative proportion of cells in each state that determines whether BAT succeeds or not. That is why BAT seems to work better in men with mHSPC or with early (asymptomatic) mCRPC. I think that what Denmeade should do is biopsy metastases and count the various phenotypes of PC cells. He will then be able to mathematically model BAT.
Well it is plausible, not bullshit. There are several mathematical models that have been proposed. Plausibility is one of the criteria we use to accept a causal link.
Yes there are many hypotheses of the complex relationship of T with PCa. We do know that the simplistic idea that T is fuel for PCa is wrong and indeed has no supporting evidence. As for the rest, we just do not know. Plausability cannot be a criterion for a causal link. Simple logic tells us that. The relationship is much more complex than previously assumed.
This always confuses me and I’m sure others here. If as you say “the idea that T is fuel for PC is wrong and indeed has no supporting evidence“, why does suppression of T usually reduce prostate cancer?
Think of it like this: PCa is happiest within a range of testosterone. That range is roughly the first quartile of normal testosterone range. About hypogonadism or a bit higher. PCa is unhappy the further T ranges from its ideal environment both below and above. In fact Huggins (who discovered the T connection) hypothesised that very high T might inhibit PCa.
Another way: think of water. Without it we die. With the right amount we thrive. But too much water is fatal.
I do know my PSA was normal when I was taking Androgel, raising my 300 T to 600. It is when I stopped taking it in 2016 that it seemed to begin to develop, resulting in a GG3 in 2019-2020. But again, this could be coincidence. No one knows.
T certainly fuels cancer. Morgentaler's "saturation theory" says that for non-metastatic men, the androgen receptors (AR) of the prostate are fully saturated at a fairly low level of T (around 100-150 ng/dl). Adding more T is like adding water to a sponge that is already sopping wet - it doesn't get wetter. At castration levels, the AR is inactivated.
But all bets are off after there are metastases. In metastases, the AR is "upgraded," meaning that the cancer produces more ARs on each cell. The cancer becomes super-sensitive to even the tiniest bit of androgen. This is part of what occurs as the cancer becomes "castration resistant." That's why Lupron is never stopped.
Kaptank and others completely misunderstand Morgentaler. Saturation Theory is only meant to apply to the prostate, not metastases.
so why isn't orchiectomy used for every metastatic case? I mean, why deal with these ADT drugs when the necessary action is to eliminate testosterone? I realize I probably am getting into this discussion way late.
Physical castration has psychological implications for many men, in its finality. (Makes it a bit hard to do an ADT vacation, too!) Personally I would/will choose it over "Lupron-for-life" if it comes to that.
Thats it? Psychological implications for a couple of nuts the size of raisins that will never produce test again justifies billions in hormone therapy? Something is not adding up
A lot more is going on than just saturation of ARs.
If you believe that (the "saturation theory") then you cannot believe that "T is fuel for cancer." They are just 2 inconsistent propositions. You cannot have both. Which is it.
Finally you have selectively misrepresented Morganthaler.
Once again. In non-metastatic PC, T is fuel for prostate cancer up to the point of saturation. In metastatic PC, there is no point of saturation because the AR is amplified.
Please enlighten me as to exactly how I've misrepresented Morgentaler. According to his work, which I've read, and you obviously haven't, I'm describing his saturation theory exactly right.
They are not incompatible. That's Morgentaler's whole point.
I prefer to think that you are mistaking his work out of ignorance of his work, rather than because you are purposefully misunderstanding it. I was trying to be less offensive by giving you an out.
You either have not read Morgenthaler or you are deliberately misrepresenting him. You certainly have not read Mahommed et al - the classic review of what we know about the effects of very high T on PCa. You misrepresent the Transformer trial and "massage the statistics" for most of the older trials you have referred to.
My thanks Tall Allen and the other contributors to this post. In support of the hypothesis that early BAT may be useful I offer excerpts from a study by Schweizer."Bipolar androgen therapy (BAT) in men with hormone sensitive (HS) prostate cancer (PC)."
Men with asymptomatic HS PC and low metastatic
burden (N = 20) (no visceral disease, ≤ 10 bone
metastases, no lymph nodes > 5 cm short axis
diameter) or non-metastatic biochemically
recurrent disease (N = 13) were enrolled.
Following 6-months of ADT, those with a PSA < 4
ng/ml went on to receive 2 cycles of BAT. A cycle
of BAT was defined as intramuscular testosterone
(T) cypionate or enanthate 400 mg on Days (D) 1,
29 and 57 followed by ADT alone D 85-169.
Results:
Twenty-nine of 33 patients received BAT following
the ADT lead-in (1 withdrew consent, 3 had PSA >
4 ng/ml). The primary endpoint was met, with
17/29 men (59%, lower bound 90% confidence
interval = 45%) having a PSA < 4 ng/ml after 2
cycles of BAT. Ten patients receiving BAT had
RECIST evaluable disease, and 8 (80%) objective
responses were observed (4 complete; 4 partial).
Three patients progressed per RECIST criteria and
3 had unconfirmed progression on bone scan.
Men treated with 6-months of ADT had improved
QOL after the first cycle of BAT. The median
improvement in SF-36, FACT-P, and IIEF total
scores were 3.2 (range, -20 to 48; P = 0.21), 3.5
(range, -30 to 50; P = 0.04), and 10 (range, -4 to 59;
Great conversation gentlemen and ladies. Just remember when we take a hard stance on a subject we are all different what works for you doesn't work for me and so forth. We can participate and be interested in treatments but even in or after a trial whan approved they may not work for everyone. Doesn't mater if your pint is half empty or half full.....its still 50 percent. Thats Science!
Thanks Allen for keeping science as the foundation for decisions. I did a high-t clinical trial. Kind of helped but also not good for me due to genetic variation in my PC. Certainly important research and one I hope will continue to explore and refine.
BTW- This is why testosterone is NEVER given to symptomatic castration-resistant patients: "94 per cent with symptomatic relapse after endocrine therapy experienced unfavorable responses [to exogenous testosterone] within 30 days of treatment. "
Wrong The only significance of the 3 month story is that is the time it will take you to figure out if BAT works for you. Then you can either stop or keep going. That is the protocol (in part)
"The primary endpoint of this trial is to determine the feasibility of the administration of transdermal testosterone alternating with enzalutamide. High dose testosterone has shown activity in phase II studies of patients with castration resistant metastatic prostate cancer; however, these studies have generally employed the intramuscular formulation. It has been hypothesized that the transdermal formulation will show activity but will have less potential for toxicity due to extremely high levels of circulating testosterone (i.e. thrombotic events). In addition, this will allow for a steady state of elevated testosterone, rather than the peaks and troughs seen with the IM approach."
Sam Denmeade:"I expect that most of the therapies I provide will either work or not work. We have treated a large number of patients at this point, and the disease of some of the patients who receive testosterone progresses, but the rate of tumor progression in these men does not seem to be accelerated by testosterone treatment."
So according to SD, we should not assume that BAT has "made matters worse" in terms of progression when men progress on BAT. Some men also progress on ADT, but we can not assert that the ADT itself has CAUSED the progression. Same goes for BAT.
And as far as "making matters worse" with regard to pre-existing pain, no one on this forum to my knowledge has ever suggested BAT for symptom relief of metastatic pain. Quite the contrary.
Men pursue RP, and it can fail. Men pursue ADT, and it can fail. Men pursue BAT, and it can fail.
He should read his own study. See notes above that are from studies with his name attached to them. Of course, the only way to know for sure is to do a randomized trial, which has never been done. There was no "pre-existing pain" because all men in trials so far have been screened to be asymptomatic,
I am less concerned with patients who are doing one of the trials at Johns Hopkins, than I am by patients who are being misled about the risks by your and others' posts. I guarantee you that patients in Denmeade's trials have to sign a waiver acknowledging that the experimental therapy might make matters worse.
Explain exactly how patients are being misled about risks in my posts that explicitly state that BAT falls outside the SOC, that they risk failure, pain and progression, and that BAT is still an unproven, experimental and risky therapy.
When you write, "Men pursue RP, and it can fail. Men pursue ADT, and it can fail. Men pursue BAT, and it can fail." you are setting up an equivalence between BAT, an experimental therapy, and RP and ADT, which are not. They aren't even in the same league.
So I guess when Keynes wrote, “in the long run we are all dead” he was misleading people about the risks inherent in life, and implying for example that there was an equivalence between smoking ten packs a day and not smoking at all? Because both lead to death. Or perhaps his statement does not address risk.
In fact, let me add to my statements above, and note that men also pursue AT (alternative treatment) and it fails and men also pursue NT (no treatment) and it fails. That in no way implies ADT = BAT = RP = AT = NT in terms of their relative risks, because it is not a statement about risk so much as a statement about mPC being an incurable disease where ALL treatments typically end in failure.
Now, YOU are welcome to infer that because I state that mPC is incurable and all treatments (or non-treatments) fail and that some patients then die (of mPC) that I must mean the risks of all treatments are equivalent, but you don't need to worry that too many men will make the same mistake as you. Nobody will.
When Sam Denmeade said "most of the therapies I provide will either work or not work" he was not setting up an equivalence between them. What he was effectively saying is, we don't always know why they either work or don't work, and if men progress on high-T we cannot merely assert that the high-T ALWAYS causes the progression. In saying that, it no way implies that the high-T NEVER causes the progression.
What he says is, we don't really know, and the only way to know for sure is to do a randomized trial, which has never been done. Ooops... it was YOU who said that, not him.
When you say BAT may make matters worse, don't forget to also say BAT may make matters better. To men who want complete information, that matters. (To men trying to scare those men, it of course doesn't matter.)
The scarecrow repeatedly tells people "it is incurable..it is incurable" without knowing that life itself is incurable....Even people who do not have PCa also die...sooner or later. Life in the end.. ends up failing...everyone's life ! Take it easy.
Or is it your opinion that if someone says "North Korea could lose a war" and then state "the U.S. could lose a war" it someone means that the U.S. and North Korea are equivalent?
Sorry TA, I don't think NK and the U.S. are even in the same league. Yet it is a perfectly logical statement.
Methinks that grammar and logic aren't your strong points. Stick to sarcasm and humor. You're great at those.
Ummm. Gee, I must have missed the word equivalent. My bad.Guess I should stop teaching classes and writing books.
Thanks for the invigorating discussion. As usual you fail to disappoint.... now please excuse me while I go back and read for the mythical "equivalence".
This is getting tiresome. You clearly do not know much about what is known of the mechanisms by which T and PCa interact. (and if you think BAT is a 3 year dose then you have been reading a different literature to me)
In a constructive spirit may I recomend a very good paper By Mahomad etal. I think it was about 2015. There have been more recent ones but I don't think they advanced the discussion. It was on the mechanisms of BAT. Very useful but it made my head hurt. I don't have the reference to hand. Life is short and I don't have time to go down every rabbithole. You will however find it in one of my posts so have a look there.
I think it may even have been my own post on the risks of BAT. It would have been scholarly of you to have referred to it.
Apparently there are a number of folks here who relish BATTING things back and forth. I'm guessing there are few men facing this stage of disease who have the background to make an intelligent decision on who makes the stronger argument here. Personally, as one of those naive types, I'd probably try to locate the most "deep in the weeds" MO I could, consider what I was told on studies that seem to be relevant, and decide. Generally, I'd advise men to be leery of anecdotal evidence.....even studies with maybe dozens, but not at least hundreds of participants. Though dozens certainly better than n=1.
Good advice. I rarely take someone's word for something. Do your own research. Practice skepticism. If you can test something, do it. Consult with doctors. But my experience is that there are doctors who seem to know considerably less about basic biology than I do. And there are others who put my knowledge to shame.
Some individuals thrive off of sitting behind a computer screen and putting down others. Let them have their enjoyment.
I've learned to take a different approach with them. I like to predict how mean they will be when someone disagrees with them. I also like to watch the 3rd grade emotions come out. If you let them run on they can be great entertainment. Free! No crowds or lines.
Thanks for the facts about BAT. Some years ago, Dr Sam Denmeade began a trial of BAT at John Hopkins Hospital in Baltimore, and I don't read much advocacy about how well it works. I did consider getting Testosterone from one of the many body building supply places where undercover sales of T are known to happen, and then just shoot myself up once each 3 months and watch results on Psa. But I'd have needed a prescription for Psa test, and any doctor will not consent to anything that is basically illegal.
But I soon got bone mets after I considered BAT, and Dr Sam Denmeade recommended strongly that BAT is a big mistake for a man who has bone mets, mainly for bone pain reasons.
To me, adding hyper doses of Testosterone tri-monthly is like pouring petrol on a fire.
The theory of large T increase in blood will overload Pca cells with too much Pca to cause Pca cells to die is a bit too simple or good to be true.
My Pca I had originally was "Puff The Magic Prostate Grenade" and I've been sitting on the darn thing since it formed in about 2004. Its been trying to explode since then, but docs have slowed down the explosion, but my Pca Grenade is organic, and many of its molecules have run away to hide and grow in my bones where its very hard to for cheeky doctors to kill the Pca molecules. Anyway, The Only Things that could deal killer blows to my nasty Pca has been Lu177, partially successful, and now Ra223. In other words, I needed to dose myself up with the kind of radiation that comes from Nuclear Explosions. So far, I have had only one dose Ra223 on 26 Feb 21, and Psa rise of 2.7 times per month has slowed, and although Psa is now about 300, I am still able to cycle 200km a week, without any Pca symptoms.
But it seems much of the terrifying Psa rise could be due the new mutated form of Pca that was first seen after 6 x Lu177 doses in PsMa scan in Nov 2020.
I have ZERO real knowledge on what the outcome may be after another 5 doses Ra223, and I asked the doc looking after Ra223 admin if he knew of what we could try after we get to the point where no more Ra223 can be safely given, and I still have some form of Pca that wants to live and grow to kill me.
My blood DNA analysis in Nov 2019 showed not one reason why I got Pca.
But I might be able to get DNA analysis of samples of remaining Pca, and then be more likely to give a treatment that might work. My doc said new treatments are likely to be trialed, maybe soon enough for me, and then he said some odd things seem to work, according to anecdotal evidence from clinical doctor experience, so May have to become the Full Laboratory Rat and be experimented on by hopeful docs.
But if I had nothing to lose, then why not?
I've considered asking Germaine Greer for a small sample of her bone marrow to be transplanted to my bones, and just about anything male about me is certain to be exterminated. The side effect of course, that we would regret, is that I end up a real Grumpy Old Lady.....
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BAT: Bipolar Androgen Therapy: A Paradoxical Approach for the Treatment of CRPC.
Bipolar Androgen Therapy for mPCA
Bipolar Androgen Therapy
Androgel for bipolar androgen therapy
Bipolar Androgen Therapy
