Cancer is Better Understood as a "Com... - Advanced Prostate...

Advanced Prostate Cancer

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Cancer is Better Understood as a "Complex Adaptive System"

MateoBeach
MateoBeach

Recently received a valuable prospective from T_A in a recent discussion on the difficulties of hormonal adaptations of PC. He drew my attention to the view of cancer as a "complex adaptive system" (CAS). This is clearly a valuable perspective or lens through which to look at the bigger picture of cancer and therapeutics.

Attached below is link to a slide show on this topic from Arizona State. It is easy to follow and get the main ideas without having to swim in the deep end of cellular signaling pathways! Some main ideas I will highlight. (I don't mean to sound like a lecture, etc. I just think it is very useful for us.):

casi.asu.edu/wp-content/upl...

The difference between "complicated systems" and "complex adaptive systems" is that merely complicated systems (like man-made machines or networks) have low intrinsic freedom. 2) Have predictable behavior and thus 3) Behavior is fixed and not capable of autonomous evolution. While complex adaptive systems, such as the weather & climate, stock markets, geopolitics, predator-prey systems, pandemics and cancer have 1) Emergence - new properties emerge from interactions of simpler units. 2) Thus cannot be reliably predicted. And 3) The "whole is more than the sum of its parts". Therefore 4) New and unexpected patterns of interactions shift the system to new and different (unpredictable) states.

Quoting: "The behavior of all complex biological systems is defined by Darwinian evolution" -Including: Variation (heterogeneity in tumor clones and sub-clones); Evolvability (adaptation to selective pressures including the tumor micro-environment, the microbiome, the immune system responses and to our treatments); Ultimately changing fitness to adapt and survive leads to the "relentless" emergence of new properties and adaptive clonal evolution in cancer.

To me this shows that we need to prepare to adapt and continue to change up the game, hopefully staying one step ahead of evolutionary adaptation in the cancer. Fixed strategies may be doomed to failure, but we can learn new ways to change things up. That also "emerges" from the ever shifting landscape of research and trials. Fight on my friends.

96 Replies
oldestnewest

Very good description. I cycle many things. PSA progression, cancer scans, and blood metric results all cause me to change my therapies. They suggest to me that my cancer has adapted.

An interesting thing is that my PSA has gone up 4 times and stayed elevated or continued climbing. 3 of those times I did a 2 week keto cycle and each time my PSA dropped. The last time it went up I didn't do a keto cycle and yet it dropped anyway (I did change up some other things).

Could be coincidence and I don't put a lot of stock in keto. But at least intriguing and quite unexpected. But only N of 3 so...

I'm not sure what my SPT threshold will be (perhaps PSA>0.1?). I have a few strategies in mind though and will be trying them before my PSA gets up to my overall SPT threshold.

depotdoug
depotdoug in reply to RSH1

What is SPT? I should already know that but its newer....

RSH1
RSH1 in reply to depotdoug

Supraphysiologic testosterone. Fancy wording for super high T.

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

depotdoug
depotdoug in reply to RSH1

Great now ive got an after lunch study lesson- High T high T.

RSH1
RSH1 in reply to depotdoug

You're welcome :)

My personal history, therapies, and hormonal plan:

History: prostatecancer.health.blog/...

Current therapies: prostatecancer.health.blog/...

Hormonal plan: prostatecancer.health.blog/...

Most of it isn't SOC except for the RP and estrogen based ADT (estrogen isn't SOC now but was for decades). I have an SOC onc though and, after my cancer didn't abide by the experts' predictions for the first six months or so, she now tells me to "do what I'm doing because it's working".

depotdoug
depotdoug in reply to RSH1

Agree with you RSH1.

In fact I've asked my Med Onc (male) and his RN (female) a couple times that I Exercise twice daily and love it. E.E.C. (excessive exercise compulsion) Doug i call me. Both above PCa support med folks above the same thing. "do what I'm doing because it's working".

RSH1
RSH1 in reply to depotdoug

EEC. Describes me. I have to force myself to take off days. It's kind of disturbing but I start getting the blues if I take more than a few days off.

depotdoug
depotdoug in reply to RSH1

History, therapies, hormone plans. How do you track all of these health positive life goals?

Impressive blog stories.

RSH1
RSH1 in reply to depotdoug

Thanks.

I used to be an engineer. So Excel. Also word for a daily log.

depotdoug
depotdoug in reply to RSH1

I’m also a retired electronics communications eng technician since 2011. Early retired 7m after my SCA.

Retired nothing to due with cardiac arrest, due to total company cut-backs on Eng/techs, 120 salaried long term employees. I can due MS word, Excel, document, report research.

Thxs RSH1.

Scary Pictures ! Are you scared enough ? Happy Halloween.

Fear is the key . Why there is no mention of prostate cancer in these slides ?

Do they also think that prostate cancer does not rise to the level of other cancer country club members ? An oncologist said " Prostate cancer is not really a cancer-cancer...most people die WITH it...only a very small number die DUE to it." Interesting though.

MateoBeach
MateoBeach in reply to LearnAll

That view has nothing to do with this perspective which is on cancers in general, therefore including but not limited specifically to prostate cancer.

Justfor_
Justfor_ in reply to MateoBeach

In cryptography very-very long code generators produce streams that for our current technology look random, while they are just chunks of very-very long periodic streams. Equally with cancer ignorance is confused with randomness.

monte1111
monte1111 in reply to Justfor_

Hi. At first I thought this was a joke. I am definitely confused with randomness ignorance. I think you called me stupid. Anyway, enjoy.

LearnAll
LearnAll in reply to Justfor_

True. When we do not understand something.. we label it random. Once we understand why it happens, randomness theory bites the dust.

MateoBeach
MateoBeach in reply to LearnAll

Thanks LearnAll for bringing in this related topic. Essential to any CI system is unpredictability and emergent properties or states from their intrinsic adaptability, with the flexibility that which emergent state out of all possible, cannot be predicted, even if it can be explained in after-the-fact analysis. So is that the same as randomness? I don’t know. (Prime number sequences for example are inherently unpredictable and yet are not random but follow their own order by simple rules. )

LearnAll
LearnAll in reply to MateoBeach

But the fact that when severely deprived of androgens, cancer cells find way to utilize other fuels in order to survive. If they off and on deprived ,the pressure on them is not enough to desperately become different . Basically, that is the idea behind Intermittent ADT. In Canada, China and Korea, Intermittent ADT has almost become SOC as most oncologists there are using it.

NOCanceros
NOCanceros in reply to LearnAll

Hello

My case now is in Intermittent ADT" Bicalutamide 150mg until november 18th 2020 then i will stop it and make PSA control may be every 2-3 months period and i will see what is going to happen ?????????

According to my oncologist Dr.weise he told me this nis our experience in this field.

Healthy life to every body here

George

LearnAll
LearnAll in reply to NOCanceros

Keep us posted about your outcome after stopping Casodex. Hope you turn out to be that very lucky Japanese man who had undetctable PSA for 8 years after stopping Casodex. This effect is called " bicalutamide withdrawal syndrome" .

If this hypothesis is true, then the SOC of PC has the wrong approach.

The SOC leads to castration resistant cancer in all the patients and eventually to what is called "treatment emerging neuroendocrin or small cell PC" which progresses rapidly despite of multiple combinations of therapies.

We should not forget that castration sensitive cancer (the natural state of PC) is easy to treat . Castration resistant cancer is an iatrogenic cancer. It does not exist without medical interventions.

The oncologists doing all these clinical studies with different drug combinations (SOC), should stop the dogma of ADT for life and concentrate in a different use of all the therapies available which will avoid the cancer to evolve to predominantly castration resistant cancer.

They should try to keep castration sensitive clones in a position to compete effectively with other clones which could appear because of adaptation to the therapies. The SOC destroys most or all the castration sensitive clones and the cancer evolves to castration resistant cancer.

People with castration sensitive metastatic cancer should worry more about how to avoid their cancers to evolve to castration resistant cancer than in annihilating the PSA to undetectable with the available treatments.

ragnar2020
ragnar2020 in reply to tango65

Hi Tango55,

Damn! I’m a dumb ass because I

read your posting twice, and I can’t figure out what you’ve said. I’ll keep

trying, but maybe you could

clarify it for us slow older guys. Thanks.

Jeff

Tall_Allen
Tall_Allen in reply to tango65

I would disagree with all of your conjectures:

"The SOC leads to castration resistant cancer in all the patients and eventually to what is called "treatment emerging neuroendocrino or small cell PC" which progresses rapidly despite of multiple combinations of therapies." Treatment-emergent NEPC actually only occurs in a small precent (17%) of heavily treated cases.

"Castration resistant cancer is a iatrogenic cancer. It does not exist without medical interventions." No. CRPC happens whether the patient is treated or not. It actually happens faster the less he is treated. CR is a product of the normal genomic breakdown that always occurs.

LearnAll
LearnAll in reply to Tall_Allen

Totally wrong ! Castration resistance and NE change happens much faster in men heavily treated with ADT . How do you explain that people who were on simple meds like Caso dex and natural stuff plus exercise , many did not have castration resistance for many years even decades.

Tall_Allen
Tall_Allen in reply to LearnAll

You continue to spout inane fictions in spite of my correcting you multiple times - what do you get out of doing that? CR is slower to arise in heavily treated men. This has been proven in multiple large clinical trials - STAMPEDE, LATITUDE, ARCHES, and TITAN. I suggest you do some research before expressing your invalid opinions. Casodex is not used, nor should it be used, in men who are detectably metastatic, other than to prevent an initial flare. If you want to harm yourself by ignoring science and believing your own fantasies, that is your prerogative.

hansjd
hansjd in reply to Tall_Allen

Hi Allen "Casodex is not used, nor should it be used, in men who are detectably metastatic, other than to prevent an initial flare." May I ask why you say that?

Tall_Allen
Tall_Allen in reply to hansjd

Sure. We now have convincing proof that for men with metastases, bicalutamide alone is inferior to GnRH agonists alone. We also have proof that stronger anti-androgens combined with castration are superior to GnRH agonists alone.

Well that is interesting, and Should be testable. If PC is a CIS then the sub populations ( clones) of, say HS and CR cancer cells (heterogeneity or anisotropic variation) are subject to Darwinian selective pressures. In which case ADT, as a selective pressure against the HS cells should lead to faster emergence of castrate resistance. So why would some evidence suggest otherwise? It makes me want to look deeper into the details.

tango65
tango65 in reply to MateoBeach

If you find data showing that PC exposed to non castrate levels of testosterone for long periods of time (or all the time, which could be the situation during natural evolution), becomes CRPC, please let us know. Please post the links.

I believe that in the last 70 years most or all the patients with PC have been exposed to medical treatments (iatrogenesis) causing castration levels of testosterone which is strongly associated with the development of CRPC.

LearnAll
LearnAll in reply to MateoBeach

Mateo beach, Many researchers now are publishing models which indicate that when androgen are suppressed fully for long , the androgen sensitive cancer cells convert into Androgen resistant and even worse Neuroendocrine cells. In this way, the life is shortened by this type of severe suppression of androgens.

Some notable oncologists like Laurence Koltz are proponents of intermittent ADT for this very reason. Dr Zhang at Moffit Cancer center ,in FL published many papers about the model which explains how the cells can be kept androgen sensitive for long time. In past, I have posted here some of this material...in my post "Intermittent androgen therapy benefits" about 3 months ago.

It is simple. Reducing the total population of clones has a bigger effect than selection pressure. (This has nothing to do with CAS). This has been documented in clinical trials.

OK that is good and will consider it and incorporate into my thinking . Thanks. No need to get into the political trenches with anyone here. You are too smart and valuable to us for that.

The one thing I won't abide is people who intentionally harm others.

Schwah
Schwah in reply to Tall_Allen

TA, so many of us greatly appreciate your dedication to the proven science of PC. It helps keep us on the straight and narrow and avoid the common pitfalls that our fears often allows us to fall into. Thank you so much for that. But please don’t you fall in the trap of politicizing this site. We all face enough of that outside of here. Your arguments are always plenty powerful without that added facet.

Schwah

LearnAll
LearnAll in reply to Schwah

Thanks Schwah.....did you notice I did not take the bait of tempting me to indulge in political slugfest..

Tall_Allen
Tall_Allen in reply to Schwah

Perhaps you should practice what you preach.

Schwah
Schwah in reply to Tall_Allen

I couldn’t agree more. I do not recall any political arguments I’ve engaged in on this site but it’s quite possible I have in the past. If so, thanks for pointing that out, as it would have been a big mistake on my part to do so on this forum. Either way, I guarantee I will not engage in any political rhetoric on this forum going forward and I urge the same for all participants.

Schwah

Tall_Allen
Tall_Allen in reply to Schwah

Your comment was about policing, not about political arguments. You were trying to police me. "But please don’t you fall in the trap of politicizing this site."

As for mentions of the anti-scientific rhetoric and anti-scientific institution rhetoric that Learnall espouses, I think we all should call that out when we see it. Unchallenged lies about cancer are dangerous. If you don't want to comment - don't, but it is not your business to ask me not to.

LearnAll
LearnAll in reply to Tall_Allen

You better stop trying to control other peoples right to give their opinion. .Are you a Hitler or Mussolini of this site....What gives you the f*ing right to insult other members and devalue them. I do not care about SOC pimps and no one should. We need to stay open minded to varying opinions and ideas and not be dictated and controlled by any self righteous ,narcissist who takes pleasure in devaluing others and insults anyone who dares to differ ...

I believe in peoples inherent capacity to discern right and wrong opinions...every one has a mind ..good enough to see what is best for them.

Tall_Allen
Tall_Allen in reply to LearnAll

Everyone is entitled to their own opinion, not to their own facts. You completely ignore the facts and misinform others about them. As I said, if you were only harming yourself, I wouldn't care.

LearnAll
LearnAll in reply to Tall_Allen

Do not try to scare me of harm...To me real harm is accepting treatments which hasten conversion to androgen resistance and neuroendocrine change ...I will try to avoid that by using all types of treatment interventions which have any positive evidence of any kind...SOC or Not. Last time you fought with me saying that there is no evidence that PCa , get converted to Neuro-Endocrine cancer after heavy ADT. long term ADT causes Neuroendocrine conversion. I am glad that today, you admitted that only 17% people get diagnosed with NE variant after heavy ADT. . That's an improvement.

You do not need to care about me.. I have lived a great and successful life and will embrace death when God decides its my time. And I know you are not God. You can only scare cowards showing them fear of death if they ignore SOC.

Tall_Allen
Tall_Allen in reply to LearnAll

You ignore facts once again...

It has been PROVED that more powerful ADT does not " hasten conversion to androgen resistance," it SLOWS conversion to androgen resistance.

As Aggarwal explained to you, it should never be withheld for fear of treatment-emergent NEPC. There is no evidence that ADT causes it, it is observed in 17% of men who have had a lot of ADT because they have very progressed PCa. I believe I have pointed out to you the difference between association and causation which is a common error.

I really don't give a shit about you one way or another. For all I know, you may be a very nice person. My concern is the other patients who come to this forum looking for truths, and you feed them lies.

LearnAll
LearnAll in reply to Tall_Allen

Alright...protector of the people...self appointed guardian of downtrodden and sick.

I am not getting into shit show with you as you are set in your ways and will keep singing the same songs which have been taught to you by....your ...you know who ?

Good Night now.

Tall_Allen
Tall_Allen in reply to LearnAll

Good. You are welcome to your paranoid delusions. Just stop lying about ADT causing CR and t-NEPC, and we'll get along fine.

LearnAll
LearnAll in reply to Tall_Allen

TA...you stop being "daddy" who knows it all...and we will get along fine. Do Not make it matter of your personal ego and stop preaching Only SOC and nothing else. Open the window of varying opinions and let your closed mind have some fresh air.

Tall_Allen
Tall_Allen in reply to LearnAll

As I said- it is NOT a matter of opinion that stronger ADT increases time to CR. This is a fact. You have no facts that show otherwise. Learn the facts, then form your opinions. And stop your endless ad hominem attacks against me. They only serve to show that you have no facts at your disposal.

LearnAll
LearnAll in reply to Tall_Allen

TA....Dude....you were warned last time.. not to attack me verbally first .. and I said "cease and desist" because if you attack first...you certainly will receive counterattack. Then, you repeated the old mistake of attacking me first and now you are crying when I replied to you in the same coin. Once again I say "cease and desist" Do Not attack verbally first. It will win you ...your peace of mind. Peace out !

Tall_Allen
Tall_Allen in reply to LearnAll

I never attacked you - just what you did. That's the difference. You persist in feckless ad hominem attacks. I never do.

LearnAll
LearnAll in reply to Tall_Allen

We ,the patients, will keep exploring and sharing how we can do better than your f*ing SOC. You can not stop us when we discuss dietary interventions, Exercise and Yoga , re-proposed ,.non SOC medications such as Metformin, Atorvastain, , etc, and try to find out how we can live better and longer with minimum toxic side effects.

You can live in your "Only SOC" dark hole if that,s what you prefer. We will choose SOC PLUS everything else which will help us fight this disease.

Once again, I will not attack you if you do not attack me first. No first attack is my official policy. Better learn peaceful co-existence...we are not going anywhere.

( My apology to fellow members.. ....who were disturbed by this uncivilized conversation)

Tall_Allen
Tall_Allen in reply to LearnAll

We? Us? You only speak for yourself, unless you have started using the Royal We.

I have never attacked you personally, only the harmful advice you've been giving. Stick to diet advice.

LearnAll
LearnAll in reply to Tall_Allen

Let me educate...meaning of "we" and "you" (when I use these words here)

"We" means patients and "you" means " Only SOC" peddlers. Did you get it ?

Tall_Allen
Tall_Allen in reply to LearnAll

You do not speak for patients. Do you get it?

cashlessclay
cashlessclay in reply to tango65

Here is some background material concerning why "undetectable PSA" may not be the best approach for best long term outcome.

journals.plos.org/plosbiolo...

nature.com/articles/s41467-...

tango65
tango65 in reply to cashlessclay

Something to discuss with the MOs. I certainly did and I am planning to use it.

Best of luck.

LearnAll
LearnAll in reply to tango65

I have used it by being on intermittent ADT...9 months ADT..then, 9 months of No ADT....now on bicalutamide and finasteride. My MO finally agreed and said "fine..but keep a close eye on PSA and ALP" . PSA at 0.6 and BALP at 10.7. As soon as PSA touches 4.0, will go back on Lupron until Nadir reaches again.

RSH1
RSH1 in reply to cashlessclay

Thanks. Good information that aligns with the goal of living with PCa.

These references are very interesting. Food for much thought indeed! Thanks for sharing them.

There are adaptive mechanisms for trade off between conserving and protecting the body in times when food may be scarce etc. and reproduction is deferred vs. expending the bodies resources in times of plenty. Early reproduction vs survival mode for later reproduction. This trade off is seen throughout nature. So how might castrate T actually be working via immune and epigenetic mechanisms to down regulate reproductive function (including the prostate) in favor of protective and survival. Perhaps a larger picture of how ADT might be functioning?

On the other hand, if the low T is a signal that reproductive life is over then the “disposable soma” theory of senescence says that our life is no longer needed for the species and irreversible damage to cells, mitochondrial and genome are the slippery slope of course. This sad view has a glimmer of hope if “grandparent gene”mechanisms activate protective mechanisms. Love your grandkids if you’ve got ‘em, and love others’ if you don’t!

LearnAll
LearnAll in reply to tango65

Tango, I fully agree and understand your point. Before the defenders of SubStandard of care jump in furiously <Let me say this...it may be a provocative truth:

The establishment wants you to be castration resistant ,therefore they give heavy duty ADT which creates androgen resistant clones and neuroendocrine variants. Then of course, it becomes more and more profitable as now, you are in a losing position and more fearful of death. Now they come up and sell you their 20000 dollars a month pill to which the cancer becomes even more resistant. finally it makes the cancer become Neuroendocrine type and they offer you exotic type of chemotherapy....This is a dirty game. If you try to expose them, they get angry and accuse you of being unscientific and demand randomized controlled trials which their cronies conduct with their money.

In Canada , Intermittent ADT is becoming more and more common as it delays castration resistance and delays NE transformation indefinitely.

SOC mafia feeds a lot of mouths including some here on this forum who go crazy as soon some one like you raise questions. They are intimidated by alternative opinions and possibilities because it has potential to drop their huge profits and jobs of these SOC advertisers can be in jeopardy. You and your loved ones are pitted against this profit making monster who will never allow simple, less harmful and equally good treatments along with complementary stuff like herbs, spices, physical exercise , relaxation etc. They want you to forget that immune system have to be addressed and stimulated...they are scarecrows and fear inducing is their main weapon. God save men and their families and loved ones.

tango65
tango65 in reply to LearnAll

I agree in many things you said.

l have been in this game for 18 years since diagnosis of my locally advanced Gleason 7 and 8 PC, because I could stop the standard of care for about 10 years.

Fourteen years ago, 2 doctors at the Dana Farber gave me about 5 to 7 years survival if I started ADT.

I did not start ADT and I looked for other treatments . I had normal testosterone values during those 10 years and the cancer did not become castration resistant.

Now, we have people saying : " CRPC happens whether the patient is treated or not."

It is very difficult for me to believe that PC will become castration resistant if it is exposed most of the time to normal testosterone values. I believe that in the last 70 years most or all the patients with PC have been exposed to treatments causing castration levels of testosterone.

Castration levels of testosterone in PC patients are mainly caused by medical interventions (iatrogenesis) and it is the main cause of the development of CRPC.

LearnAll
LearnAll in reply to tango65

Yes..more and more people are understanding what you are saying. Glad you had the courage to go against SOC. I am trying to follow your path as I think we need to avoid/delay CRPC as long as possible by using all available means.

Tall_Allen
Tall_Allen in reply to tango65

Genetic breakdown is the biggest driver of cancer progression. The AR becomes resistant because (like all other parts of the cancer cell) it is constantly changing. Such changes as internalization of the AR and activation by new kinds of ligands make the AR of the cancer cell naturally less dependent on external androgens and occur even if androgens are plentiful. Those mutations are more "successful" so they take over.

tango65
tango65 in reply to Tall_Allen

Data speak clearly. Please refer to studies showing that the natural evolution of PC is to become CRPC even when exposed all the time to non castrate values of testosterone.

Tall_Allen
Tall_Allen in reply to tango65

I just gave you two examples- look it up. This may help you understand:

cell.com/cell/fulltext/S009...

tango65
tango65 in reply to Tall_Allen

Thanks, I have been reading about all these mechanisms for a long time. I have a cancer with PTEN loss which affect the PI3K/AKT pathway. I found some clinical trials which could be useful.

By the way the article you posted does not answer my request and I does not use the words testosterone or prostate cancer at all.

Tall_Allen
Tall_Allen in reply to tango65

Actually it does answer your question. The hallmark of metastatic cancer is unrestrained genomic breakdown. It occurs no matter what we throw at it. It is relentless. The one thing we've found for prostate cancer that slows it down for at least some time is ADT - the more powerful, the longer it slows it down.

MateoBeach
MateoBeach in reply to tango65

Understand completely Tango. Trying to sort this out and reconcile your experience which is reasoned and coherent with evidence claimed to the contrary. Somewhere behind this seeming contradiction there must be a coherent and correct perspective. Glad you have done so well outside the SOC box.

BTW my inclination is that the PTEN PI3k AKT pathways hold the central keys along with mTOR and Sirtuins and AMPK regulation of transcription via histone deacetylation mechanisms. But I struggle to try bringing complex adaptive systems view resonated with me . Keep on keeping on!

Event

Unfortunately, there are many growth pathways. If you block one, another will crop up. The cancer is infinitely inventive because of unrestrained mutation and quick reproduction.

tango65
tango65 in reply to MateoBeach

I agree. I think PTEN loss plays a very important role in the progression of the cancer, along with P53 and RB mutations.

After BCR , my PTEN loss PC have had consistently a PSADT of less than 2 months.

Such aggressive cancer did not become CRPC during the 10 years the cancer was controlled without using ADT and exposed to normal testosterone levels.

I just want to see DATA showing that ADT slows down the "unrestrained genomic breakdown" of PC . I would also like to see DATA showing that PC can evolve into CRPC when exposed continuously or very frequently to normal testosterone values.

If you find something please let us know.

Tall_Allen
Tall_Allen in reply to tango65

You don't seem to be convinced by the data showing that genomic breakdown is normal and expected as cancer advances. And also you don't find convincing the fact that androgen annihilation delays the genomic changes that cause CR Perhaps you have data showing that testosterone can prevent it? Doesn't the burden fall on you to provide proof for an idea that is so contrary to the proof providedd by clinical trials?

tango65
tango65 in reply to MateoBeach

Thanks.

Best of luck on your journey.

pjoshea13
pjoshea13 in reply to tango65

At the beginning of the PSA era, when there was a big jump in PCa detection in the US, there followed a small but unexpected bump in PCa mortality. At that time, before Medicare put its foot down, doctors who gave Lupron shots were getting $1,000 a shot. A urologist once told me "We were all doing it." With the profit motive removed, doctors discovered that Gleason 3+3 men did not need to be rushed into ADT. It seemed clear to me that some had been rushed into early death.

The U.S. currently has >3,000,000 living men who once had a PCa diagnosis. About 192,000 new cases each year, but only 33,000 PCa deaths. It's a small number, considering the reductions in competing mortalities that have occurred (lung cancer, heart attacks, etc.) The mathematics do not support the idea of relentless PCa progression. In fact, the idea behind active surveillance is that progression from GS=3+3 often does not occur.

With Abiraterone & Enzalutamide we have seen the appearance of forms of "treatment-emergent" resistance that were not a problem in Lupron resistance. One never heard about AR-V7 before Abi & Enza.

But one could read about other forms of resistance that occurred with Lupron, such as androgen receptor amplification. And researchers were quite clear about the reason - androgen deprivation. AR amplification does not occur in men with normal androgen levels. Non-curative treatment selects for resistance. CRPC is not inevitable - by defination it is resistance to castration. Whr would it occur in the absence of castrate T?

After failed surgery & radiation 16 years ago my doctor told me the "Some would say that you need to begin hormone therapy." But classic ADT fails within 18-24 months for most men. Why use up palliative therapies when one is not in need of palliation. Some men cling to the idea that early treatment is always better & might against-the-odds be curative.

With regard to the statistics, I was initially puzzled when I read that 70% of men with mets would be dead within 5 years, until I realized that most men with PCa do not progress to the metastatic state.

For a young man with mPCa to believe that SoC is the best option, it's a fatalistic acceptance of an early death. One reads of advances that might add months to life expectancy, but nothing that will add 10-20 years.

To reject science-based complementary approaches is not to reject magical thinking - it's to give up.

-Patrick

ragnar2020
ragnar2020 in reply to pjoshea13

Patrick,

Thanks for this comment. Internet forums such as this one need men with a knowledge of PCa treatment history in order to properly evaluate the recommendations of their care

givers.

Jeff

RSH1
RSH1 in reply to pjoshea13

My initial prognosis from Mayo was a bitter pill and I'm glad that I didn't swallow it. But at that time I had no idea I had other options and their slate of surgery, radiation, chemo, and ADT, followed by death, put me into a mental tailspin.

I had surgery but rejected everything else. Mayo docs "guaranteed" that my cancer would return aggressively within 3 months of surgery. Unless I did ADT. In which case I would extend my life enough for radiation. If I did that I'd likely extend it enough for chemo. If I survived all of the treatments I might live for a decade or two.

I don't know what will happen in the future but at least I've gotten by their 3 month prediction (been almost two years since surgery).

I feel the way you do, excluding everything other that SOC is to accept low QoL and an early death.

tango65
tango65 in reply to pjoshea13

I agree Patrick. Thanks for your comments.

I wonder if you could explain what you have been doing with your treatment. It would be nice if you could do a separated post from this chain which has become difficult to follow.

Do you know of data showing that PC exposed frequently or permanently to testosterone becomes CRPC?. or data showing that ADT delays the genomic breakdown or mutational burden of PC?

The clinical trials are not evidence of ADT delaying genomic breakdown of PC. They show that ADT plus anti androgens or chemo has a survival advantage. My understanding is that the new anti androgen are blocking mutated parts of the AR which explain a longer control of the cancer.

Best of luck.

Tall_Allen
Tall_Allen in reply to tango65

"The clinical trials are not evidence of ADT delaying genomic breakdown of PC. " In addition they all show that genomic evolution to castration resistance occurs later in men who are heavily treated. "the new anti androgen are blocking mutated parts of the AR which explain a longer control of the cancer" If you agree that they block AR mutation, I really don't understand why you think anyone is better off without them. You seem to be contradicting yourself.

pjoshea13
pjoshea13 in reply to tango65

Hi Tango,

I'm not going to start a separate post on my 16-year use of testosterone because I'm not trying to make converts. When people ask, I explain, but I don't want to promote my current strategy, even though Dr. Sam Denmeade at Hopkins has made it somewhat repectable.

In 2004, before baby boomers made PCa such an attractive research field, one could read almost everything that PubMed had on the subject. I was struck by a hypothesis from the 1990s. It suggested that many men could reset the clock with T after ADT became refractory, and that the cycle might be repeated a number of times.

I thought this was optimistic. Why wait for what was called 'hormone insensitive' [CRPC] to set in? I came up with a maximum time period for ADT use - 3 months. Long enough to have a meaningful effect on PCa & hopefully not long enough to select for characteristics that could not be 'deselected' via T exposure.

Ideally, IMO, BAT should be started at the same time as ADT. There is no proof yet, since Denmeade began on men with CRPC in his early studies. (Easy to find volunteers in that demographic.) Still, the results were encouraging.

There is plenty of evidence that low T at diagnosis places a man at risk for poor survival. Given the increasing acceptance of active surveillance, one might have thought there would be an intervention study. But there is still a reluctance to give T to men with PCa. The lawyers perhaps. lol

My feeling is that the risk with TRT occurs only after men have been conventionally treated for PCa.

I wasn't even born when Huggins began his work, & yet, here we are, still targeting the androgen receptor [AR] axis. Castration by itself only buys 2 years for most. Throw in an antiandrogen & we get a little longer. Inhibit all androgen generation (Abi) & so on & what are we up to in average survival? But with ever-increasing sophistication we select for ever-increasing cell-survival sophistication. The cancer always wins. It's like trench warfare on the Western Front in WWI.

-Patrick

tango65
tango65 in reply to pjoshea13

Thanks Patrick.

LearnAll
LearnAll in reply to pjoshea13

Thanks Patrick..I could not have said it better.

When financial incentives are wrongly given.. pathological greed reigns the system and cause havoc with patients and their loved ones.

Don't you remember...only in last 2 decades...Urologists were removing everyones prostate gland who had some increase in PSA...whether it was due to prostatitis, BPH or just normal high secreters.

That earned American Urologists a nick name " Prostate snatchers" Then, came the

new lutamide gang and started promoting these highly toxic drugs whether some one really needed or not.

And now, their are lot of whispers of neuroendocrine conversion and early castration resistance which this evil lobby is trying to suppress just like Cigarette Companies did in their last few years. Some times , some SCO pimps possibly paid by big pharma appear on these sites posing as patient advocates to push their agenda. Beware.

OK T_A. This was not directed toeebut I am about half way through that extensive list of factors contributing to malignancy and proliferation. It just makes the point of the unpredictability and adaptive flexibility of the process. It does not make the case for why one approach should be persistently superior when maintained. I am still asking

why continued ADT would not favor emergence of castrate resistance.

tango65
tango65 in reply to MateoBeach

I am waiting for the same data.

Because it doesn't. The clinical evidence proves it. And in a BIG way.

BTW- you may be misinterpreting what I was saying about CAS. I brought it up in reference to BAT, guessing as to why it's effect is so limited. I'm hypothesizing that there is only a narrow window of opportunity during which it can be held in a meta-stable state. Genomic breakdown will ultimately collapse that state.

kaptank
kaptank in reply to Tall_Allen

I did that experiment. BAT until failure, rechallege (bicalutamide), failure: can it be repeated? 3 cycles at best, then PSA above designated failure (all tripling the use time of Bical). Consult onc. PSMA etc scan a surprise, 2 old lymph mets halved, spot on a rib after 3+ years, then PSA test a third of previous - all just continuing bical. Something happened. Case of one, but invaluable to me. It tells me to intervene with supra T occassionally, stringing out use of bical.

LearnAll
LearnAll in reply to kaptank

I like your experiment Kaptank. It enhances the point that after subjecting our body to unnatural, physiologically abnormal state caused by ADT....when you release the pressure of ADT and add T to the system, you are basically taking the body towards a normal physiological state. This repeat cycling of these two states is possibly prolonging time to develop castration resistance. Results of your experiment are showing it.

Tall_Allen
Tall_Allen in reply to kaptank

I think your results would have been better with a more powerful anti-androgen. It often makes metastases completely disappear. 3 years is typical with it. I hope that BAT with it may be even more.

kaptank
kaptank in reply to Tall_Allen

Point taken. My use of bical is a historical accident. BAT does seem to extend the use of enza and abi in many cases and there are indications it might go well with PARP and checkpoint inhibitors given the right genetics. We are still learning about the potential uses of this tool in the toolbox. I see it as an adjuct to SOC, not a replacement.

Last year a speaker at a Detroit symposium described prostate cancer as "a meadow, not a cornfield." A good mid Western metaphor that his audience understood.

MateoBeach
MateoBeach in reply to dadzone43

In California-speak I suppose they would say it is an eco-system and not a monoculture.

Heyyyyy Abbott "who's on first?"

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/08/2020 6:26 PM DST

tango65
tango65 in reply to j-o-h-n

You know who is first, always first. Please pass the ice cream, I need some. I am really tired ,

j-o-h-n
j-o-h-n in reply to tango65

It's in the mail................

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/08/2020 8:00 PM DST

MateoBeach
MateoBeach in reply to tango65

You guys are the best. This thread has been exhausting but has taught me so much. Thanks to all who contributed. Now going for a Rocky Road.

tango65
tango65 in reply to MateoBeach

Best of luck, and thanks for posting.

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

From a rocky road to a rocky road.........

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/08/2020 9:24 PM DST

tango65
tango65 in reply to j-o-h-n

I did not get the ice cream.

j-o-h-n
j-o-h-n in reply to tango65

Sorry,

I think it may have gotten mixed up with the mail in ballots and actully voted for two guys, one for president the other one for vice president (Ben and Jerry).....

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 10/08/2020 11:20 PM DST

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