Thanks to Tall Allen I have read some solid studies that say combining treatments is best for overall survival, for personal reasons I am on 150 Bicalutimide monotherapy, these reasons were a severe loss of strength which I thought maybe it was because of previous hormone therapy, in reality it was IBM muscle disease. Using Bicalutimide I hope I can keep strength going longer.
I post the numbers for interest sake on effect of Bicalutimide for now I am going with Monotherapy, when it fails I hope the other methods will work and give extra time. I am not aware of a study that investigated mono therapy for example start with Bicalutimide then Zoladex, then add Zytiga, next Xtandi or some formula like this. The ones I saw all start with hormone therapy and then add something else. So anything where you start with Zytiga first or Xtandi holding Lupron for last.
I know Magnus 1964 has had success when on mono, I think mono Bicalutimide Is popular in Europe if anyone knows of studies sequencing one at a time please let me know.
The other question I have is last summer I had 3 bone Mets treated by SABR, my testosterone is slowly rising now on Bicalutimide but PSA low, does Bicalutimide work as well as Zoladex on bone Mets if PSA is undetectable. If no PSA can bone Mets grow. If bone Mets grow would this not cause PSA to rise.
June 2020 under .008. .2020-06-23 10:09 AM
Ga <0.008<4.5
2020-03-12 12:01 PM0.012<4.5
2019-12-15 09:58 AM0.032<4.5
2019-10-21 11:08 AM0.048<4.5
2019-07-29 02:09 PM0.083<4.5
2019-04-26 08:56 AM0.26<4.5
2019-01-17 11:03 AM6.6<4.5
I went on Bicalutimide in February 2019, but when 3 bone metastases were discovered went to Zoladex in May, then back to Bicalutimide in December. .008 is pretty neat, hopefully I get some time,
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Canuck53
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Nice! I just started bicalutamide (w/finasteride + tamoxifen). Hope my PSA does as well.
That testosterone is slowly rising should not be a concern, since bicalutamide is targeting AR and not the androgen production. After about 5 weeks, my PSA went from 31 to 6.4 while T went from high-normal (700 range) to high (1100 range). No worries here.
I also have three mets (spine) but do not plan any SABR on them unless until I "need" to, because of progression or pain. Could the mets grow even if PSA stays low? I think they COULD, but I'm going to assume they will not. I will be optimistic at least until the next scans (in a year?) either confirm or destroy my reasonable assumptions.
Whenever this therapy fails and mets are progressing and/or PSA climbs, I will trust my MO to offer whatever SOC is statistically "superior" at that point. You are right about needing to look to non-US studies, though, since American MOs are far less likely to be familiar with whatever research exists regarding best outcomes for men starting therapy w/ 150mg Casodex (definitely NOT normal in the US).
But my own intuitive inclination is to try a BAT approach (supra-physiological T therapy) as a follow-up. Any evidence this is a good idea? No! Will my MO want to do this? No! But if I get a few years out of this before failure/progression, perhaps one or the other of us will have had a change of mind by then?
In the meantime, here's to a (hopefully) higher QoL than standard ADT for us!
I had my Mets done in a small clinical trial, 5 treatments on spine, 5 on ribs, it is not a year yet but for now I would do it again, there is a chance the results could be solid.
Obviously micro Mets are the concern, but it buys time regardless. I am in Canada 150 Bicalutimide is not SOC but allowed by some Docs.
If I was lucky like others to get 3 to 5 years out of it then I think worth it.
I did BAT after bicalutamide +zolodex failed and it reversed resistance for a period. I have had a few attempts at repeating the sequence and I recently did SBRT on 2 lymph and 1 rib met. Currently trying a different sequenced approach from what I have learnt so far and from experience of Patrick (PJOshea). Bical originally failed after 12 months, first BAT after 8 months and bical rechallenge after another 6 months. Currently 3 years since first bical fail and PSA staying within a 0-4 range. I think it good to stay on bical as long as possible but be prepared to bail when it really fails as in that state, it encourages PCa. I will post an account of my continuing "experiments" when I have solid data. Meanwhile my profile has past posts on the experience. Check also with posts from Patrick.
14. Clinicians should offer ADT with either LHRH agonists or antagonists or surgical castration in patients with mHSPC. (Strong Recommendation; Evidence Level: Grade B)
15. In patients with mHSPC, clinicians should offer continued ADT in combination with either androgen pathway directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel). (Strong Recommendation; Evidence Level: Grade A)
16. In selected mHSPC patients with low-volume metastatic disease, clinicians may offer primary radiotherapy to the prostate in combination with ADT. (Conditional Recommendation; Evidence Level: Grade C)
17. Clinicians should not offer first generation antiandrogens (bicalutamide, flutamide, nilutamide) in combination with LHRH agonists in patients with mHSPC, except to block testosterone flare. (Strong Recommendation; Evidence Level: Grade A)
18. Clinicians should not offer oral androgen pathway directed therapy (e.g., abiraterone acetate plus prednisone, apalutamide, bicalutamide, darolutomide, enzalutamide, flutamide, nilutamide) without ADT for patients with mHSPC. (Expert Opinion)
Now that you know you have IBM, is there any reason to continue with the monotherapy?
PSA is not a useful biomarker for tracking progression after you have zapped your bone metastases. This is called "treating PSA" instead of treating the cancer, which is micrometastatic and systemic.
Thanks, just after I posted that article I noticed you posted yours. My thought is Bicalutimide allows for some more muscle reception, the IBM is not good so strength retention is a priority.
Do you have an opinion on muscle retention on Bicalutimide vs Zoladex.
Any articles on undetectable PSA and bone Mets, is bone Mets based on testesterone only or is PSA a factor.
For as long as PSA is low is there not some thought just go with it, what is your thought when it fails go on Zoladex would Zoladex not work as well or does Bicalutimide affect the strength of Zoladex.
My question is does going on Bicalutimide first affect the quality of Zoladex if you go on it next.
You state Zoladex works against metastasis better, but if you have no PSA do Mets grow, my thought when Bicalutimide fails then go on Zoladex is There any merit to this.
"My question is does going on Bicalutimide first affect the quality of Zoladex if you go on it next." Delayed use of Zoladex, for any reason, means that it will not work as well.
"You state Zoladex works against metastasis better, but if you have no PSA do Mets grow, my thought when Bicalutimide fails then go on Zoladex is There any merit to this." PSA is the result of metastases growing and creating tumors with their own blood supply. If you get rid of only those tumors large enought to have their own blood supply, you will lower PSA. But most of the millions of cancer cells in your body do not have their own blood supply and don't create much PSA in the serum. It is a really bad idea to only treat metastatic PC with bicalutamide and delay use of Zoladex.
Thanks again Allen, I am guilty of treating PSA believing undetectable is everything, it is very informative about micro cells and no PSA, big decision coming up.
To be clear I chose no ADT strictly hoping my muscle strength would decline slower on Bicalutimide.
The other thought in that article the expert opinion is combine the various ” Mides” with adt not Monotherapy this is based on perceptions.
What If the question was asked of the experts based on the premise Monotherapy could keep PSA undetectable for years would there advice be different, I don’t think it has been studied enough so it is a bit of a cookie cutter answer.
Let me repeat... keeping PSA undetectable is not the goal - the goal is to keep you alive as long as possible. You have to let go of the thinking that PSA is cancer - it isn't.
I have no idea what you mean by "mides" - do you mean weak anti-androgens like bicalutamide, or strong anti-androgens like enzalutamide? The combination of strong antiandrogens and castration has been studied extensively. They provide superior survival to castration (chemical or physical) alone. Castration provides superior survival to weak antiandrogens. This is all irrespective of whether PSA gets to undetectable.
I meant all the new generation ones, thanks you have answered my questions nicely, the whole thing comes down to how much more strength I will lose on ADT. Risk/reward.
My situation is a little different death with IBM disease or PC I think PC will be my choice as IBM takes over the body just end treatment.
"is there any reason to continue with the monotherapy?"
Sure... one reason would be that one doesn't belong to the church of the AUA. Faith in "expert opinion" is still faith in an opinion. Biased experts continue without pause, almost daily, to prove how wrong they can be in so many areas... or at least how biased.
"As a surgeon, my expert opinion is, you need surgery. rather than radiation"
"As an RO, my expert opinion is, you need radiation. rather than surgery"
Really? But men have been reporting this for decades.
Fortunately, the expert opinion of the surgeon or RO who claims "he got it all" is wrong only about half the time. Or is it? Well, as long as he ignores the micro-metastases, and never bothers mentioning them to the patient...
You seem to misunderstand what it means when the AUA says it is "Expert Opinion." "Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there may or may not be evidence." You probably don't know the names of the doctors who are on the panel, but they include many top urologists, medical oncologists, and radiation oncologists. In addition, there was an extensive peer-review process:
"Peer Review and Document Approval
An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a thorough peer review process to ensure that the document was reviewed by experts in the diagnosis and management of Advanced Prostate Cancer. In addition to reviewers from the AUA PGC, Science and Quality Council (SQC), and Board of Directors (BOD), the document was reviewed by representatives from ASTRO, SUO, and ASCO as well as external content experts. Additionally, a call for reviewers was placed on the AUA website from December 2-16, 2019 to allow any additional interested parties to request a copy of the document for review. The guideline was also sent to the Urology Care Foundation and representation from prostate cancer advocacy to open the document further to the patient perspective. The draft guideline document was distributed to 96 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 44 reviewers provided comments, including 34 external reviewers. At the end of the peer review process, a total of 522 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the AUA PGC, SQC, and BOD as well as the governing bodies of ASTRO and SUO for final approval."
Their discussion of Guideline 18 should be acknowledged by anyone who wants to defy the guideline:
"Non-steroidal antiandrogen therapy without ADT in advanced prostate cancer is not recommended. Evidence based on 11 studies encompassing 3,060 patients suggests that use of non-steroidal antiandrogens without ADT compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of OS, clinical progression, treatment failure, and treatment discontinuation due to adverse events. 88
Bicalutamide, flutamide and nilutamide are first generation antiandrogens extensively studied in combination with either bilateral orchiectomy or LHRH agonists in mHSPC. 89-93 There is insufficient evidence to support the use of first generation antiandrogens as monotherapy. 89,94-96"
So I think you summed up why I think it is faith-based.
Pick any of the 11 studies that purport to show antiandrogen inferiority and I'll be happy to tell you why I don't think they actually show that. The Tyrell study that shows lower survival for men with metastases, for example, fails to subdivide them. Would I recommend Casodex monotherapy as initial treatment for a man with very advanced PC with a PSA of 500 and a heavy burden of mets? No. But that apparently would be roughly representative of most of the cohort of men who showed significantly better survival with standard ADT over bicalutamide in Tyrell's study. Can the observed statistical inferiority for that unlucky group of men be extrapolated to oligometastatic men with much lower PSAs and Gleason scores who are beginning treatment? I don't think so.
And while there may be "insufficient evidence" to support the use of first generation antiandrogens as monotherapy, can you provide the sufficient evidence that RP is superior to antiandrogens?
RP was falling out of favor in the 60s and 70s, partly because docs saw the frequency of later PC recurrence. Did it make a comeback and become the "gold standard" because of a sudden appearance of evidence that pointed toward PC being a local disease rather than a systemic one? No. (Evidence was actually pointing the other way.)
Perhaps, in large part since (via Walsh) there were better outcomes as regards side effects, RP was to come back into favor and become the "gold standard" in a manner achieved by consensus for which there was no good evidence. Where was the new evidence that RP was superior to systemic therapy, so far as cancer-specific survival over the long term?
Yes. This is faith-based as AUA is the cult of SOC parrots who push the same agenda to achieve their own narrow ,selfish goals.
30+ years ago, when a doctor used to evaluate a patient , the doctor,s first assumption used to be all cases are regular, non aggressive cases until proven otherwise by evolving symptoms and other data about a patients condition.
So, the doctor used to start with milder, safer treatments that worked for many many patients. Some patients would display aggressive variants and the doctor would tailor his treatments according to aggressiveness and other features.
In last 30 or so years, the assumption has been changed totally. Now, the assumption is that every patient has aggressive case until proven otherwise.
So ,here comes SOC..which is usually decided by financial vultures of Onco industrial complex. . If they start with assumption that every case is aggressive, then it gives them license to load up every patient with multiple very expensive treatments which make lot of profit for them. Then those toxic treatments destroy the body by severe side effects..that gives them excuse to treat those side effects with more expensive treatments. SOC parrots are helped by lawyers who scare and intimidate good doctors who wants to use their own judgement.
Sometimes, some people like noahware and canuck figure out this conspiracy of unnecessary, over-treatment and rebel and take their treatment in their own hands . ( i did too)
Boy..that needs a lot of balls as fear is the weapon used to promote SOC.
"Selfish" goals? Those doctors have devoted their lives to helping patients. Who are you to impugn their motives? Your paranoia/conspiracy theories may interfere with your own health, and if anyone believes your fictions, may harm the health of others.
You are making up fake history. 30 years ago, medicines available for prostate cancer were milder, but didn't increase survival as much. They were not taken because they were "milder," they were used because that was all we had. Before docetaxel, only mitaxantrone was available. It did not increase survival. Docetaxel proved that it could increase survival and QOL. Mitoxantrone was abandoned.
The STAMPEDE trials (and CHAARTED and LATITUDE and others) proved that earlier use of chemo and more powerful hormonal agents like abiraterone, enzalutamide, and apalutamide could extend life more when used in men who were newly diagnosed with metastases. Your disdain of science is harmful.
I know doctors are good people but when they get bought by greedy companies , some of them lose that good, humanitarian side.
Do Not takes my logic to extreme..My main point is that every patient is unique and treatment should be provided based on detailed clinical, biomarker and imaging data. And not just by putting every one on a bunch of treatments in the name of SOC.
You are being paternalistic by telling me that I will suffer if I don't agree to the point of view of all powerful "tall" Allen.
I do have constitutional right to express my opinion and who are you to stop me.
People have their own intelligence to sort out what is good for them after hearing different points of view. You need to drop your God Father complex and allow others to express their opinions.
" but when they get bought by greedy companies , some of them lose that good, humanitarian side." Who? Which ones? Figments of your fevered imagination do not constitute reality.
Someone needs to stand up against people like you who make unsupported pronouncements, and ignore science. If you don't want to hear what I have to say - it's easy - don't respond to me. I assure you I never read whatever you post if it doesn't land in my inbox as a response to me.
"I know doctors are good people but when they get bought by greedy companies..."
I almost fell off my chair reading that unsubstantiated slander. Shame on you LearnAll!!!
Read this to learn how unbribeable doctors, around the world, are:
"Novartis AG and a former subsidiary of the Swiss drugmaker agreed to pay a combined $347 million to resolve allegations that the companies ran schemes to bribe public hospitals and clinics in Greece, Vietnam and South Korea, U.S. authorities said Thursday."
You are calling me idiot just for expressing my opinion. You are a coward...Calling people names is an act of cowardice. I can also call you M*f..sob..moron, trash and so on...BUT I will not stoop to your low level.
Learn to be civil to others otherwise you will remain disgusted for rest of your life.
Science is always by consensus, and always has been and always will be. .As Popper showed, an experiment can never prove a fact, it can only falsify the opposite. That's why all research studies in the last century start with a "null hypothesis" that the study can only disprove with a certain "consensus" degree of confidence. All the paradigms of modern science, including climate change, natural selection, and quantum mechanics are only accepted by consensus. Kuhn showed that changes in consensus sometimes occur, which he called "paradigm shifts."
Subgroup analysis of any study may be invalid. The scientific consensus is that it is only even potentially valid if the subgroups are specified upfront , the subgroup is sufficiently powered, and the conclusion is plausible and consistent with other observations. For an amusing discussion of why subgroup analysis is problematic, a STAMPEDE investigator uses subgroup analysis to "prove" that men born on Mondays are more likely to benefit from abiraterone, but men diagnosed on Mondays are not likely to benefit. What you are proposing is the kind of research that gives statistics a bad name.
I certainly can provide evidence that therapies like RP and RT can be curative, whereas hormone therapy cannot. RP never "fell out of favor" as you mistakenly aver. However, Walsh's development of nerve sparing prostatectomy in the 1980s certainly made the therapy more popular. I wouldn't call it the "gold standard" but it is certainly curative for well-selected men.
Well, of course. How could it not be, when the group of the "well-selected" might include those whose cancers were destined to never become symptomatic or lethal even without RP? In men who do not need cure, RP has a 100% success rate.
You are missing the point about sub-grouping. If "the consensus" says men being studied are essentially homogeneous with respect to the disease being studied, and decides to ignore many potential differentiating factors (which do NOT include day of diagnosis), does that mean the men actually ARE homogeneous? Of course not. And to assume so for the sake of convenience is unscientific.
The collection of SOME evidence that POINTS towards a conclusion does not mean the desired conclusion can be stated as established "fact." What can be stated is, evidences suggests the conclusion may be true.
(The consensus thought that high-T therapy necessarily "feeds" PC progression was based essentially on the evidence of ONE single patient of Huggins. Very unscientific. But "experts" pronouncing this as a fact said they had science behind them, simply because they were scientists.)
What you call "paradigm shifts" are often just a case of actual science overtaking the non-science of the expert consensus, . The real shift was that baseless assertions were exposed as being incorrect.
Michael Crichton:
"Historically, the claim of consensus has been the first refuge of scoundrels; it is a way to avoid debate by claiming that the matter is already settled.
Consensus is the business of politics. In science consensus is irrelevant. What is relevant is reproducible results. The greatest scientists in history are great precisely because they broke with the consensus. There is no such thing as consensus science. If it’s consensus, it isn’t science. If it’s science, it isn’t consensus. Period.
The track record of the consensus is nothing to be proud of. The greatest killer of women was fever following childbirth. One woman in six died of this fever. In 1795, Alexander Gordon of Aberdeen suggested that the fevers were infectious processes, and he was able to cure them. The consensus said no.
In 1843, Oliver Wendell Holmes claimed puerperal fever was contagious, and presented compelling evidence. The consensus said no.
In 1849, Semmelweiss demonstrated that sanitary techniques virtually eliminated puerperal fever in hospitals under his management. The consensus ignored him and dismissed him from his post.
In the 1920s in America, tens of thousands of people were dying of a disease called pellagra. The consensus of scientists said it was infectious. Goldberger concluded that diet was the crucial factor. The consensus remained wedded to the germ theory and continued to disagree with him. Despite a twentieth century epidemic, the consensus took years to see the light."
LOL@your quoting Michael Crichton, a fiction writer, as your authority. No doubt he saw himself as the Nietzschean übermensche fighting the consensus on climate change. You are clearly not a scientist (as I was). It is possible that a patient is the single exception to all the rules. I've seen patients on here who believed that they could cure their prostate cancer with curcumin or somesuch. Maybe they are right. That was the stance taken by Steve Jobs, to his eventual regret. Good luck with your belief that you are the exception.
Talk about laughing out loud. Using an "appeal to authority" is especially amusing when one claims his OWN opinions carry weight, while those of others do not, because of HIS credentials. (Dumb old Crichton was just an ignorant Harvard BA and MD, after all.)
Why do you think I was quoting Michael Crichton as "an authority?" Did I say he was? Which "authoritative" qualifications would make his passages more or less true? Could he be an historian who studies scientists and science, or would he have to be a practicing scientist?
The reason you assumed I necessarily must see him as "an authority" is because that is how YOU operate: the more-qualified expert is ALWAYS right, by virtue of his qualifications alone.
So let's consider the patient who believed nutrition was a factor in pellagra and that sanitation was a factor in puerperal fever. That make YOU the qualified "expert" who tell the unqualified patient he/she is wrong, because that's what the consensus says: we, the (factually incorrect) experts, shall regard those who ARE (factually) correct as being obviously incorrect (at least until such time as we no longer justifiably can).
This has nothing to do with one's belief that he alone is the exception. It's the observation of MANY exceptions and variations in outcomes, the knowledge of PC as a HIGHLY heterogeneous disease (making "men with PC" a HIGHLY heterogeneous group), and the observations in the limitations and flaws of statistical analysis that can ignore relevant factors.
Any study that simply lumps "metastatic" and "non-metastatic" into two homogeneous groups with no other qualifications (like prognostic levels 1-5, or "oligometastatic" status, etc.) is one that I will probably see as flawed. So the stats coming out of that study will be flawed. That does not mean that NOTHING isn't learned from such a study, but it surely means that not EVERYTHING is learned.
Science is incremental and continuously creeping while the consensus is restrained by inertia, moving in stops and starts, and often with a significant lag time.
It was not "the consensus" itself that determined it would be wise to re-evaluate the Gleason score and include higher grade cancers in the score even if they reflected only a small percentage of core samples. The consensus FOLLOWED the science of the FEW who observed and analyzed post-RP outcomes, and made that suggestion. The prior surgical consensus of the urgent "need" to remove Gleason 6 prostates was shown to be in error (because it was a BUSINESS consensus).
It is not the consensus that did the science, but the science that pushed the self-appointed expert consensus to increasingly admit what ACTUAL science had already observed: lots of low-grade PC will prove to be harmless. That during the PSA-induced "RP boom" only a few surgeons refused to do RPs on 80-year-olds with asymptomatic Gleason 6 did not make them "wrong." Just one example.
I guess you didn't bother reading my post. (Although I have noticed that you often prefer NOT to address salient points.) I am not relying on any authority. I quoted Crichton because of the examples he cited, which point to failures of "the consensus." Are you suggesting those examples are invalid?
And nowhere do I say the consensus is never correct. My point is, it is not always correct. The establishment consensus often starts from beliefs, positions that are merely assumed. Science questions the consensus when some doubt reasonably exists about prevailing beliefs. The consensus sometimes replies "the assumptions are already settled, so do not keep asking questions or offering alternative possibilities." Are you suggesting that is incorrect?
As for Crichton, I have no idea about his theories on global warming, nor do I care. Why should I? TA's apparent logic: a person who believes one thing, and is wrong about it, loses all credibility on all other subjects.
I am going to assume TA has been wrong about something. By his own logic, we should then assume he is not an authority on anything, and he appears to be telling us either to 1) disregard his assertions, or perhaps 2) assume he has never been wrong.
Canuck53 wrote: "I think mono Bicalutimide Is popular in Europe"
This is not the case, it is rarely used. However, in some countries the guidelines allow to use it against PCa. E.g. the UK guidelines, called NICE, write:
"1.5.9 For people with metastatic prostate cancer who are willing to accept the adverse impact on overall survival and gynaecomastia with the aim of retaining sexual function, offer anti-androgen monotherapy with bicalutamide"
One of the best threads I have read it’s great to get the different information. My history is Lupron and BIcalutamide because of Mets the decision to forgo radiation and switch to Xtandi with Lupron was made . I am say after 1 month the side effects with Xtandi are much stronger than the BIcalutamide.
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PSA rising .01 - .08 in 6 months
Welcoming good advice
PSA Rising While on Lupron and Zytiga
Climbing PSA
Docetaxel/Taxotere. 2nd time in 3 years. It's a no go this time. No benefit after 3 infusions.
