As I followed my Pca story, I have now changed focus from straight genomic mutations [AR mutations,etc] to what I see as a new focus on how Pca treatments induce senescence and how this senescence is a double edged sword. The following clinical article is a newer view:
The above figure is from this article [couldnt get the second figure to be added, it keeps replacing the first??]
From a previous thread on this subject, I got the sense that our Pca treatments first can effect aptosis and actually kill the Pca cell and then the treatment tends to produce these senescense cells that have a good and bad side, as shown above and described in the article [hopefully the above link works.
In my case, I am trying to ascertain the optimal strategy, given I have already progressed on 2 sequential AR monotherapies [xtandi then erleada]. They have just started me on relugolix ADT. My PSA is now very low after just emerging from undetectable, I am sure it has acquired a more aggressive nature and can therefore progress rapidly from here, so in my view, the current low PSA is temporary. Also, I am sure I already have a lot of senescence cells.
Given the above, does it make sense for me to add another systemic therapy such as chemo [which I never had], perhaps inducing more scenescense, with the above associated good/bad duality? What about Provenge, which the article doesnt address? Does Provenge also induce senescence?
How do you chose and optimal strategy. Would appreciate your views.
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podsart
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Just an aside. Provenge was withdrawn in uk and Europe. Is it still available in US?
May I ask your age and general state of health and fitness? I guess the perspective I have is the need to balance quality versus quantity of life.
My personal view! Leaving aside the science for the moment, the problem with current approaches to CaP is that therapy progressively drives cancer cells in a Darwinian fashion towards greater de-differentiation. In PCa it selects for treatment resistance and for example, the growth of undifferentiated neuroendocrine tumours.
We are locked into a model which says T is the fuel when maybe just maybe it is not, or at least not that simple. The literature on the role of T contains contradictions. A recent lab study in Nature Comms showed T had biphasic effects on PCa cells with high levels causing differentiation and inhibiting proliferation. Estradiol is just as good as ADT at suppressing CaP without many of the side effects (PATCH). The BATMAN approach uses high dose T to “re-sensitise” CaP in advanced resistant disease. T therapy in patients with CaP does not seem to exacerbate the disease. Maybe, just maybe, current therapy models are wrong. But what do I know!
It leaves a lot of questions and as a result I am opting for the least possible therapy for my CaP to minimise adverse effects and maintain good QOL. At age nearly 79 I aim to keep as fit as possible, stay away from my ex-colleagues and hospitals (I am retired physician) as much as possible and carpe diem.
Question everything you are told and don’t be driven by fear.
Yes, Pca ,like othe cancers and even certain viruses have developed a complex adaptation process to survive, leading to " undifferentiated neuroendocrine tumours" and perhaps small cell and other non PSA types. I am famliar with the biphasic nature of T, as I had a long period of supra T [1600] for a long while while on Xtandi. I am interested in BAT, however, it is a risky venture as there are those whose Pca respond to BAT with an acceleration of their Pca. Not aware of a way to tell beforehand. I have asked my Dr to talk to Dr Danmeade re BAT for me.
Love the carpe diem quote. Unfortunately, I am not one of the bravest patients. Regardless, all of us are forced by reality to make a policy decision re quant vs qual to some extent.
Estriadol is a controversial treatment. I was a patient of Dr Myers before he retired and he use Estrogen patches frequently. When I transfered to Dr Drake, who received a number of ex Dr Myers patients,he found a number of them who were deveoping blood clots on the estrogen , even though they were on the patch type treatment. Some have told me to make sure your E2 is in the 20 range and not much highe,r to help with our Pca.
On the estrogen PATCH trial - big study and power and convinced me its a better option. So I think the controversies are now answered. My experience of ADT and ARIs has not been good so stopped the lot. PSA beginning to creep up so planning to ask for patches this time. Especially as I have stroke history and ADT pushed my TGs up.
Depending on progress I might try to push for T replacement. Monitoring though is tricky as PSA synthesis but not necessarily PCa growth is stimulated by T and DHT. All rather complex.
I assume you re in the US whereas I am UK near Exeter so use the oncology service at Royal Devon and Exeter Hospital.
Sorry! Triglycerides - not good. Fasting levels went up to 3x normal along with increase in abdominal fat. . I am not normally overweight, stopped the drugs, removed all sugar from diet and stopped all alcohol for two months, and shed 5 kg.
I like to question everything but my MO feels we are arguing when I question. He says next step is Docetaxel as Psa has started to rise. I need that before Pluvitico which to him is a great drug. I am doing great with a great quality of life and in no hurry for the chemo side effects. Next Wed I see Dr. Samuel Denmeade at John Hopkins in Baltimore. It’s an hour and a half drive but I will be seeing a doctor who specializes in prostate cancer. I have interest in BAT but will wait to see what he says. My MO that I now see actually refused to test my T levels. That caused quite the discussion. God bless
My Uro told me he had a patient on lupron that was doing well with a very low T. The firm he was at for some reason switched everyone on lupron to the other drug that is to be the same, can’t remember the name. Patients Psa started to climb shortly thereafter. Another T test was taken to determine if Psa was rising because patient was becoming castrate resistant or not responding to the different drug. T level had risen so patient was put back on lupron and Psa dropped. Had there not been a T baseline there would be no way of knowing it was the drug that caused the failure and the patient was not castrate resistant.
I had my T tested when I refused to change from 1 Abi with breakfast to 4 abis without food. Results were less than 1 or undetectable. Doc still wanted me to take 4 without food. My Uro tested T when he put me on lupron and it was 13 each time. My Uro insists if you put a patient on a testosterone lowering drug you monitor the T at least every six months.
It is interesting that it does not seem to be considered here in uk al least in my experience. I shall make some enquiries. I guess the proof is in the falling PSA or not.
If I don’t message you by next Sat, Dec 21 message me. I will tell you that I read some reviews, which are all 5star, and one guy said he drives 1000 miles to see Denmeade. I do know that the first appointment must be face to face. And I have been told there is a test to determine if you are a BAT candidate and it is only given at John Hopkins.
Professor Gary, what Docetaxel chemo side effects are you concerned about? I know people have varying results and in my case I religiously used ice on hands and feet, had the anti-infection injection, and fasted two or three days around each session. And the side effects during the six sessions were not bad at all, I have no neuropathy, and am unaware of any chemo specific side effects. Starting from a Stage 4B diagnosis almost 3 years ago, I'm doing pretty good so far (chemo is part of triplet). Today's chemo is not their horror stories from 20 years ago. I don't know if my own anecdote is helpful, but there it is.
It's a very good question. Because he says the result would not affect treatment. It angers me but has not as yet caused me to change docs. Another doc has ordered a few T tests for her own reasons, so at least I have some idea.
Personally I think it is irresponsible not to check for testosterone escape. Particularly for longer term treatments like injected lhrh agonists ascopubs.org/doi/10.1200/jc...
There is no evidence that it impacts BCR but logically it is not ideal.
I prefer Orgovyx daily tablets (available in the Uk since August 2024) where dosage is better controlled.
My GP will order whatever tests I ask for but I don't ask for a lot.
I don’t know if I’m late to the party, but when I asks my mo about pluvicto, he said that once you do it, it takes away many trial options afterwards due to what it does to platelet levels. I also have not done chemo and that’s the pre-requisite. Instead he has me doing a phase one immuno therapy. Full disclosure, I was satisfied with his reasoning so I did not look any further into it, but thought it important to share.
I’m in the same position as you, I went ahead and had Provenge a couple of years ago when PSA first became detectable after a long period of (6years ) of being undetectable. I’ve been playing whack a mole for the last two years now, when PSA reaches 0.2 I get a PSMA scan determine the source and have SBRT, both times PSA has fallen close to undetectable and stayed there for nearly a year. Sartor, my oncologist says I can do this indefinitely based on number and location of mets. If that’s no longer an option I’ll probably give BAT a try.
Yes Sartor moved to Mayo in Minn. I saw him at Tulane for several years after Snuffy retired, that was a drive to for me since I live in ATL area. I’ve traveled to Mayo once but stay in contact by phone with him for now unless things go sideways and require a trip to Minn. My mets were initially throughout my skeleton at dx, last couple of scans showed a met on a rib that I had treated.
That’s a reasonable question. Basically, I have had a 2 year string of monthly undetectable PSAs and then it has just turned detectable. I have just started orgovix with a hi starting T will take a while to get to castrate, so my next labs will effectively be another clean data point.
On orgovix you should turn castrate almost immediately? That is my understanding. Why don't you ask for firmsgon injections just to avoid that for some reason nobody can temper with your oral medication in order to..? You should know better what you are doing?
Androgen deprivation therapy (ADT) for conditions like prostate cancer is often administered via injections rather than orally due to several reasons:
1. Controlled Release: Injectable forms, such as depot preparations, allow for a slow and sustained release of medication, ensuring consistent therapeutic levels over weeks or months.
2. Avoiding First-Pass Metabolism: Oral medications are metabolized in the liver (first-pass effect), which can reduce their effectiveness or increase side effects.
3. Patient Compliance: Injections given every few months reduce the need for daily medication, improving adherence.
4. Reduced Side Effects: Some oral ADT medications can pose higher risks for liver toxicity or other systemic effects compared to injectables.
If oral medications are necessary, close monitoring is essential to manage any potential risks. Always follow medical advice tailored to your condition.
I’ve been on organix for years, same results (t=<12) and milder hot flashes. I’m an example of one, but with all due respect, this sounds like it was cut and pasted from the firmagon marketing white paper. Not trying to be mean.
Maybe I am just paranoid. If it is working for you that is great. I want to say that I like a certainty of the firmagon injections and I actually started to consider bilateral orchiectomy. I am not recommending that but I am thinking hard about that. You must be young and most probably curable in that case orgovix is great. I am diagnosed long time ago I have enough of injections plus I can't always recall if I took my medication or not and that sort of thing. Maybe we are just simply not in a same league. I apologise if I said something contrary to your beliefs.
No need to apologize; it sounds like you're processing a lot of thoughts and making deeply personal decisions. Your perspective is valid, and it's clear you're carefully considering what works best for you given your history and current situation.
Choosing between treatments like Firmagon, Orgovyx, or even a bilateral orchiectomy is deeply personal, influenced by factors like your medical history, lifestyle, and comfort with the treatment regimen. It's completely understandable to want certainty and simplicity, especially if you've been managing this for a long time.
For some, the idea of an orchiectomy offers peace of mind and eliminates the need for ongoing medication or injections, but it's a big step and one worth discussing thoroughly with your doctor.
You're not alone in this, and your decision will be the right one for you. If you ever want to talk more, share your thoughts, or ask about options, I'm here to listen.
podsart wrote -- " no, I don’t think that irreversible action appeals to me now "
I immediately chose a bilateral Orchiectomy in 2015 instead of ADT Drugs (5+5 dx) and never regretted it. SE's were minimal and have been on/off/on .... TRT since 2016.
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