You should not be doing anything now other than monitoring PSA. Testosterone should never be used outside of carefully watched clinical trials. It has never been tried in non-metastatic men in clinical trials. Don't get ahead of yourself - stick with what you know.
Did a study -- with patients after initial surgery/or radiation -- gave one group supplemented high testosterone replacement -- and the other half -- no testosterone replacement. At 5 years the group given supplemental testosterone 15% had bio-chemical recurrence -- the group not given supplemental testosterone replacement had 53% bio-chemical failure... Also the 15% in the group receiving testosterone were one and a half years longer before BCF occurred.
Yes, saw this in another recent post, hence me asking the question.
It looks like newer data coming in supports the the use of a super testosterone treatment plan without adverse outcomes.
I will ask my doctor on Oct 13th when I have a phone appointment about his opinion.
For myself, I interpreted the info on the video that it is now the time for me to start testosterone which of course is against all standard protocols.
You are misinterpreting it. What Khera did is treat patients who had already been cured (like me) AND who were hypogonadal (like me). Hypogonadal means they have naturally low levels of testosterone. Hypogonadal men have higher rates of prostate cancer than eugonadal men. Normal (not supraphysiological) levels of testosterone are protective. I take TRT myself, and if you're levels are low AND it is established that you are not recurrent. TRT is an option.
BAT has never been used in cases like yours, only in men with known asymptomatic metastases. Here is the research:
I don't think supraphysiologic doses will cause more prostate cancer if you are cured (in which case, you don't need it anyway), but it may cause cancer that is already in you, and is quiescent, to wake up and metastasize. I think that only a quack would let you have it.
I will admit I have a hard time understanding all the information that we subject ourselves to in this learning process, but like most people here we find little nuggets of wisdom or research that leads to a better education of our cancer.
You obviously are a great source of information to so many here and I know I've learned quite a bit just reading responses you've made to others over the years.
I'm sure my doctor will say something similar to what you have stated.
You have to wait for your testosterone to normalize, of course. My doctors (Uro and RO) were willing to give me TRT after 2 years at nadir PSA, Although I still have a prostate, my PSA has not increased with TRT.
You make the point that Khera’s cohort was cured yet a large percentage of them were recurrent. Do you mean they were “ thought to be cured”? You further point out his cohort was hypogonadal suggesting extrapolation to non hypogonadal men is fallacious. That may be true. But perhaps you could explain why. My conception is that hypogonadism is T between 230 and 300 depending on age. And that level of T is adequate to feed PCA since ADT is deployed to bring T down to under 30 where the ADT sensitive cells are deprived. Non hypogonadal men have T in the 500 and above range. But the layer of T between 300 and 500 is not PCA generative since 300 is generative. If both groups get Super T what is the biology that separates the two cohorts from each other?
But whether it is merely an association or a causative factor is unknown.
Are you asking what is the biology that causes some PCa to proliferate wildly in a high T environment, while others do not? I don't know - no one does - which is exactly the reason that caution is important. My hypothesis is that it has something to do with the degree of AR expression. One of the modes of castration resistance is "upgrading of the AR." It probably begins quite early and accelerates over time. Some men then are more sensitive to even a small increase in T (which is why GnRH agonists/antagonists are always continued after CR). I hope Denmeade is looking at IHC of the AR to determine whether there is a expression cut point. That's one hypothesis. It may have something to do with the degree of AR androgen independence as well. I could go on for hours coming up with possible biochemical reasons. This is clearly not ready for prime time.
Not being argumentative TA, but you do not address the “bi-phasic” response of PCa to Testosterone, In that cancer growth is suppressed at very low levels ( castrate levels) but also by Supra-physiologic levels. And at low but non castrate levels growth is most strongly stimulated. This observation is the fuel for much research into mechanisms and led to the current interest and trials of BAT and combinations. Leibowitz pursues this with the idea that SPT May specifically shock CRPC cell sub populations and delay CR emergence. (Controversial and unproven but interesting. )
This article discusses the evidence for possible mechanisms underlying the bi-phasic T response to testosterone.
"The authors propose that utilization of high dose androgen therapy as early as after radical prostatectomy, or possibly biochemical relapse, when cancer cells are still dispersed and solitary may have most efficacy as stable induction of the self-sustained quiescent state in their studies only occurred at low cell density."
It also explains why what Liebowitz is doing is just wrong. He hasn't published anything since 2009 and even then had nothing useful. Even BAT has been a dangerous gamble for about half the men - there is a long way to go before it's ready for prime time. No one has any idea yet how to select patients who may benefit.
I understand and have read your review (a few times) and looked at all referenced as best I could. Indeed BAT has a long way to go. I was just going back to what is known (and not known) from the science including pre-clinical that digs into the possible mechanisms. The Mohammad review does a good job on this, though some surpasses my pay grade. So that was why I was interested in your take.
Interesting statement at end of section 7.7 was pointed out (on Induction of Cellular Senescence or Quiescence) that Afterglow noted: "The authors propose that utilization of high dose androgen therapy as early as after radical prostatectomy, or possibly biochemical relapse, when cancer cells are still dispersed and solitary may have most efficacy as stable induction of the self-sustained quiescent state in their studies only occurred at low cell density."
Nothing in my discussion is meant to indicate that anyone should undertake this without being in a clinical trial, or carefully informed and supervised by their doctors outside of one. Currently I am pursuing standard TRT for my hypogonadal symptoms which go far beyond hot flushes, with a T of 90 one year after stopping ADT and my PSA steady at <0.2. Hence my interest in the topics of TRT and SRT altogether.
BTW I agree with your comment about Dr. Leibowitz. His program including 5ARIs along with SRT makes no sense to me since models show that finasteride reverses the effects of SRT on LNCaP exografts.
I will read it later. Michael Schweizer is doing some interesting work in Seattle and I respect what he has to say. Thanks for the reference.
I don't know if he gets into it, but I think that at a certain state the cancer is best modeled as a complex adaptive system (CAS). Like all CAS's it is meta-stable and can be kept for a while near some rough equilibrium around a "strange attractor". At this state the periodic high testosterone maintains some sensitivity to androgen ablation. That's why I agree with you that BAT may make sense whereas continuous high T is just batshit crazy. At some point there is not enough T sensitivity or androgen ablation sensitivity and the system can no longer adapt.
One or the other is true ...either they got it all and you are cured or they didn't --
(a)First lets say -- after the radiation treatment and accompanying ADT -- they got it all --- In which case to continue the ADT you are losing bone, muscle mass, increased possibility of heart problems and dementia for no reason ...
Or (b) after the radiation treatment and accompanying ADT there is residual cancer that survived --- (it is one or the other) in which case you stay on the ADT until the PSA starts rising --- in which case you will become effectively already CRPC -- the worst kind.
Or (c) you get off the ADT and find out !! I would suggest seeing Dr. Khera -- get on high dose testosterone (which shocks any remaining PCa cell if there are any -- causing double strand breaks ) and see if it delays or prevents BCR all together -- as his study indicated it does.
If BCR occurs -- then do imaging to see if it can be surgically removed or radiated and repeat option (c) again and again if needed ... this way whatever happens you are not moving toward CRPC... you are on high Testosterone and feeling great -- no bone and muscle loss etc.
by the way I went to Toronto to get Dukoral (shown to help slow PCa ) over the counter in Canada -- not available in that form in USA -- (Dukoral was the type that was studied so I thought I should get it -- the other type in U S is a different concoction.
"Recent evidence suggests that cholera toxin might have multiple functions regarding the ability to regulate the immune system. However, it is unknown whether subsequent administration of cholera vaccine might affect the mortality rate in patients with prostate cancer. Here we report that patients in Sweden, who were diagnosed with prostate cancer between July 2005 and December 2014 and used cholera vaccine, have a decreased risk of death from prostate cancer (HR, 0.57; 95% CI, 0.40–0.82) as compared to patients with prostate cancer but without cholera vaccine use, adjusted for a range of confounding factors. In addition, patients using cholera vaccine show a decreased risk of death overall (HR, 0.53; 95% CI, 0.41–0.69). The decreased mortality rate is largely consistent, irrespective of patients’ age or tumor stage at diagnosis. In this population-based study, we suggest that subsequent administration of cholera vaccine after prostate cancer diagnosis might reduce the mortality rate."
" In Sweden, cholera vaccine is composed of inactivated Vibrio cholera O1 and the recombinant CTB subunit, which is sold under the product name Dukoral. Our study included a total of 841 patients who used cholera vaccine and 89,142 patients who did not use cholera vaccine."
Yes high T -- and yes -- locally advanced --3/2020 found quarter inch spot in prostate bed that had lite PSMA uptake had surgery 4/2016 only other treatment to date is supplements and Avodart on and off for last 2 years -- and 200mg weekly high T - 3 weeks
If you entertain SPT, remember that low levels don't foster growth, in normal levels PCa tends to thrive, in very high levels (>1500ng/dl) some or most PCa cells don't do well. Very heavy decision though. SPT appears to be working great for me and my SOC doctors are scratching their heads because they didn't expect anything close to this type of success. I don't know if it works like this for everyone though.
Whatever you do, talk to doctors, research, ask questions, monitor your PSA, monitor blood metrics, be prepared to adjust if necessary.
Yep, through this cancer journey you keep entering phases where one has to decide what is the better option or best path to follow and some decisions are harder than others.
You never want to miss a potential good treatment opportunity if you think it can help.
I saw your response and wanted to congratulate you on it. One of the difficult things to learn is that the cancer does go through phases, and the best treatment in one phase may not be the best treatment in another phase. For example, it may be harmful to treat non-metastatic men with chemo, immunotherapies, PARP inhibitors, or testosterone. There are a few trials now to learn whether treatment with 2nd line hormonals has any benefit in this situation. Understanding where you are and which treatments and research is appropriate for men at your phase is one of the things we learn.
You may be interested in this article on timing of therapies:
I was hypogonadal (due to a varicocele) and began using T cream in the late '90s. Felt great for years, but about 10 years later in '08 was diagnosed with PC. It never metastacized, but whenever I decided to try using the T again my PSA shot up, so my doctor advised that in me at least T feeds PC. I'd like very much to use T again - I just felt so much better in all ways, and healthier (in all ways but one) - but it looks like it's not in the cards for me. I really miss it. I don't miss metastases.
Note what RSH1 wrote regarding T: " low levels don't foster growth, in normal levels PCa tends to thrive, in very high levels (>1500ng/dl) some or most PCa cells don't do well"
So by raising levels low to roughly normal, you could have been feeding PC, but if you were to raise them to "very high" it might very well have the opposite effect, and start killing PC.
That does not mean you have, or are going to find, a doc willing to do this! It is still considered an experimental approach. But if you ever DO use T again, it sounds like supra-physiological levels might be the way to go. The MO Bob Liebowitz had patients with T levels in the 2000-4000 range who apparently did very well.
Interesting - using T brought my level up to 700+, which was great compared to how I'd felt previously. But sometimes I'd use more (I tend to do that with everything), and it would hit 1500, and then I felt like Superman - big waves, long hills on the bike, heavy weights. The doc told me that was too high - it could cause thrombosis and heart attack in addition to PC - so I'd sadly stash my cape and revert to being Clark Kent. Reading about supra-T gives me a bit what-if regrets.
"The doc told me that was too high - it could cause thrombosis and heart attack in addition to PC"
This seemed to be a common concern for some docs, but others assert there is not that much evidence of increased risk.
While on bicalutamide, my serum T levels have risen to over 1000, but I can't say I'm really "feeling it" as superman, since the drug blocks androgen receptor activity. I don't feel lousy, by any means, just not better.
Sam Denmeade at Johns Hopkins is the current champion of high-T for PC in clinical settings. He does have affiliations with other docs around the country. One thing he noted, is most the patients DO notice that improved mood and energy, and are disappointed when they have to revert to low-T periods, which is part of that bipolar therapy regime.
On I side note, I really wonder about any connection between varicocele and PC. I was diagnosed with it in my 20s but it had no apparent symptoms or consequences. Some have suggested that varicocele may change the hormonal balance within and surrounding the prostate and possibly contribute to PC. Another "what if" thought!
on the varicocele possibility - I'd never heard that - the varicocele made my left nut atrophy and shrink, starting in my teens, diagnosed in my 20s, one of those things that I wonder why nobody ever said it could and should be fixed, doctors said I'd be OK because my other testicle was fine - I do know that I'm the only male on either side of our family to have had PC.
My varicocele was was the doc called "a bag of worms" and not to worry. Just some extra packing material in my package, as it were. My boys could still swim.
Any link to PC is of course purely hypothetical, because there does not seem to be any well-defined correlation, so far as I'm aware.
Thanks for injecting some sanity into the conversation. Reading some of the posts from others, high T sounds like a good thing for everyone to do. It is not. No one yet knows why some men do well with BAT (sustained high T is just foolish) and some men get a lot worse. Until more is known, it is definitely not something to do outside of clinical trials.
The patients in Dr. Khera's study were obviously not cured --- 53% of the ones not started on testosterone replacement had BCR in 5 years .... and 15% of the group that received TRT had BCR. in 5 years --- only theirs was delayed by a year and one half. That is a 38% benefit in TRT after surgery or radiation and low or no PSA.
Well you were wrong I hope you understand that there are more than one meaning for T.......In this case, as you suggested in another post, Tit For Tat....you have to buy 2 vowels also!!!!
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Enzalutamide (Xtandi) or not
18 months and PSA incrdasingeklo
Raising PSA with 6 months of RALP
Prep for side effects of casodex vs zytiga and prednisone
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