Well, it looks like my honeymoons of ADT are over. I was (and still am) on a tripple therapy along the lines of the ARASENS trial (Docetaxel, Lupron and NUBEQA) for about 2 years. My PSA started rising six months ago, at first slowly, but now very rapidly. It went from 0.04 to 0.05 then 0.17 (in three months between tests and Lupron injections) and a month and a half after that to 0.3. Still waiting for the oncologist decision about what to do next. I am guessing it will be Pluvicto. It looks like I will first have a PSMA/PET scan to see what's going on. I don't have any symptoms so far, except excessive sleepiness in the morning. Used to feel OK(ish) with 6 to 7 hours of sleep prior to diagnosis and during the first two years after that. Now I am getting closer to 8, in chunks of 2-3 hours, feeling more tired in the morning than I used to. Has anybody been there already? What did you do?
PSA rising, rapidly: Well, it looks... - Advanced Prostate...
PSA rising, rapidly
Hi Oldie. Your comments on fatigue resonate. My age and diagnosis and treatment very similar to yours - coming up two years. And I'm tired too. So with your numbers rising - in absolute terms they seem very low (which is not to minimize the importance!) - do they say "resistance"? In other words resistance to NUBEQA (aka Darolutamide)? You will stay on ADT, yes? (My understanding from clinical trials is that one stays on ADT even with "resistance".) A successful transition for you to a new line of effective therapy - if you even need it! 😃
Thank you for your comments. Yes, ADT (Lupron and perhaps NUBEQA)_ are forever (like diamonds:)). It is not clear yet, but the most likely conclusion is that my cancer is getting CRPC.
I've been researching PCa therapy resistance a lot, so I'm going to get pedantic here - in case people are reading this. Technically speaking ...
1. Lupron (aka Eligard), a GnRH injectable agonist, is categorized as ADT. It suppresses the production of testosterone all the way back at the pituitary. My understanding is that ADT any flavor is the "forever" part of therapy after the development of resistance. (The other "flavor" of ADT is that of a GnRH "antagonist", such as injectable Degarelix, aka Firmagon, or the newer oral Relugolix aka Orgovyx.)
2. Darolutamide (NUBEQA), is an "androgen receptor inhibitor", acronymed as ARi. It messes up any unsuppressed testosterone that might hit the cell wall of a prostate cancer cell.
So between these two powerful therapies against prostate cancer, you can hit testosterone twice, coming and going!! It's a miracle. And the combo works really well, until it doesn't!
I'm also on triplet therapy myself, except in my case Abiraterone (Zytiga) replaces Darolutamide. Abiraterone is categorized as an "androgen receptor pathway inhibitor" or ARPI. It interferes with the manufacturer of testosterone, in between ADT from the top and ARi at the bottom of the testosterone pathway.
I've begun wondering if you couldn't do all three therapies together, at the top with ADT, in the middle with an ARPI, and at the bottom with an ARi. To my knowledge this is not done yet.
On the topic of resistance though, resistance happens because prostate cancer cells are desperate to live and are constantly figuring out ways around the fact that we are trying to kill them. Therapies deployed to kill prostate cancer cells creates what is known as "selection pressure"; in other words we are talking about evolution, at the cell level. Cancer cells don't die the normal way - only if we kill them. But sadly, new cancer cells are born all the time!
So over time, if even a few cells out of a million survive our assaults with various combinations and sequences of chemo, ADT, ARPI and ARi, then those cells will be the ones that multiply and become the dominant type of cell in our masses of prostate cancer cells. It's almost as if our success has been our failure!
This this defines the meaning of hormone or castration resistance. As one can imagine from the description of the evolutionary process there is an element of time involved. Resistance doesn't happen overnight.
Preventing this development of resistance is the whole inspiration behind BAT therapy - to mess up the evolution of PCa cell populations to where therapy resistant cells are dominant. I haven't done this and haven't noticed any reports that BAT has been astonishingly successful yet.
Okay I'm thinking out loud here and you didn't ask for my opinion. I'm facing resistance sooner or later and wondering what can be done.
There was a trial adding apalutamide to abiraterone plus ADT you might find interesting:
>Adding apalutamide (Erleada) to abiraterone acetate (Zytiga) and prednisone reduced the risk of radiographic progression or death by 30% in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) receiving androgen deprivation therapy (ADT), according to the final analysis from the phase 3 ACIS study presented during the 2021 Genitourinary Cancers Symposium.
onclive.com/view/apalutamid...
Thanks DS! This trial report you shared is very interesting, combining ADT, ARPI and ARi together against PCa. Scary high level of adverse events though. And you do get more time. But not that much more. You still need to "get your affairs in order", except that with the fatigue, including mental tiredness, that becomes more and more difficult 😃. It would be great to see if progress could be made to the point that metastatic prostate cancer (and for the also hormone-driven breast cancer) becomes "chronic" and you can just live with it. This was achieved with HIV amazingly; let's do it with hormone cancers too.
As for me, I take a few not-crazy supplements but more importantly I'm focused on exercise. My exercise program is based on the theory that the right balance, quantity and type of exercise is an anticancer therapy all by itself. It's hard to do. (I've written about this elsewhere here.)
look for ovm 200 trial and osteodex trial…. I am sure you will like them…
Can you provide links/references to these trials?
sciencedirect.com/science/a... it seems that they are waiting for some patent before moving on to phase 3
and this one:
Great advice, thanks. Exercise and resistance work, alternating cardio/resistance has worked for me as well. In addition, I've been on an exact regimen of microdosing of magic mushrooms along with lupron/erleada. It has increased mental clarity by removing brain fog. Don't think we'll ever see medical research on this however. 4 days/wk microdose, 3 off for 4 weeks. Then 2 weeks off. Keeps the body from building up a tolerance. PSA has stayed undetectable even though I still have a prostate. Don't expect to feel any "buzz" however since the dosage is tiny.
I'm not ready for magic mushrooms yet, even micro-dosing. I'm assuming it's only about cognition? And nothing about PCa directly?
It just lifts brain fog. Nothing about PC, just about side effects of lupron/erleada.
I am interested in the mushroom microdosing. Can you clarify the regimen: microdose 4 days/wk, 3 off for 4 weeks then 2 weeks off. Also, what is the formula for microdosing you use? Thanks very much!
maoi.org/health/stamets-stack/
Above is the link to the Paul Stamets site. It's the regimen I follow.
I know is worrisome but they shouldn't do anything different until there is evidence of radiographic progression of the cancer.
I was in a similar situation and it took one year and a PSA around 7 to show radiographic progression.
Continue to enjoy your life. It will take a while to change plans.
As to the fatigue, ‘John in the middle’ is right. Exercise, especially resistance training, decreases fatigue, increases muscle mass despite zero T, and is proven yo fight cancer in and of itself. Studies have actually shown more cancer fighting T-cells in your system post workout.
Schwah
Almost everyone experiences fatigue on Lupron. Aggressive weight-training is the standard answer.
My PSA is also rising post treatment, and, when indicated, I propose to start on high-dose transdermal Estradiol vs. Lupron to achieve castrate levels of T. Far more tolerable array of SEs, in terms of fatigue, hot flashes, brain fog, depression, emotional lability.
Creates gynecomastia. I don't care. I'd rather deal with it than spend my limited time on Earth in tears, wishing I were dead.
I started taking THC gummies last year before bed. Went from sleeping in 1-3 hour intervals to a full 7+. Start slow. It's amazing how it's helped me sleep. I take the type with CBD which is supposed to also fight cancer cells.
hellopharmacist.com/drug-he.... I also wish to take CBD gummies. Just thought make aware of enzyme CYP3A4. Abiraterone & CBD share this enzyme, which may altar the way Abi is assimilated.
Interesting, I stopped abi because I'm also dealing with Parsonage-Turner syndrome and was hoping my nerve pain would decrease. MY PTS is better so looking to start back up on Abi later this month.
My MO refuses to talk MCRPa timelines, but he gave me this on PSA ( I am on Lupron/abi) - I asked how the criteria of “has stopped working” works - and I got this - “We want to declare a therapy no longer effective when PSA is clearly going up. We look for 0.3 to 0.6 among the patients who are scared. 2.0 to 4.0 among the relaxed. We should wait for a PSA doubling time of less than 9 months. In either case we don’t care about number 2 or 3 places after the decimal. Anything less than0.3 is not useful unless looking for relapse after radical. Remember NCCN protocol is to start enzalutamide or apalutamide if PSA clearly rising.”
I was diagnosed in April, 2016 with metastatic prostate cancer. PSA 133. Spread to bones and some lymph nodes. Was told I probably had 5 years left. 8 years later, psa is undetectable and I feel pretty good. Treatments included radiation, of course Firmagon and later Lupron, Zyriga and Xtandi. The Zyriga worked good for several years but finally fizzled out as predicted. Xtandi didn’t work at all for me, but everyone is different. After that, clinical trials were proposed to me. First trial didn’t work. Psa went to 22. Then I entered another trial using a weekly infusion of an immunotherapy drug called Amgen 509. The results were amazing. Psa rapidly dropped to undetectable. There were some minor side effects like rashes that were easily treated. I finally got a form of vasculitis that got quite nasty. The Dr was concerned that the trial drug contributed to this so I was removed from the trial after one year. Now, one year after stopping the trial, my psa is still undetectable and scans are stable. This doesn’t surprise the pharmaceutical company although they don’t know how long that will last. It’s a trial. Bottom line is this: there is so much research and new treatments available that I don’t think you need to worry about getting you affairs in order although you should even if you didn’t have this disease. Some hospitals and doctors have much more to offer than others. The hospital I use is big in clinical trials. Good luck!
Thank you for your input. It's funny how these predictions for how long we have are thrown at us with no real data to back them up. My PSA at diagnosis was 260 and I was told I have a year or maximum two, to live, if I didn't do anything. That actually might have been correct, we'll never know. If you don't mind sharing: 1. What was the drug in the first, unsuccessful clinical trial? 2. What was your AP at diagnosis? 3. What was the lowest value of your PSA when on Amgen 509 and how long did it take to get there?
1). The first trial (that didn’t work) used a combination of Xtandi and Tazemetostat. 2) I don’t know what “AP” is. That term was never used by either of my two oncologists. They described the level of progression by Gleason score. Mine was eight. 3). I started the Amgen 509 in Jan. 2022. PSA then was 24.6. PSA test on March 2, 2022 was undetectable and still is undetectable.
Thank you very much for your answers. AP is Alkaline Phosphatase. It is mesured with blood test and indicates cancer has spread to the bones. Mine was 1200 at diagnosis, went down to a couple of hundred after 6 round of Docetaxel and I believe is still there, but starting to creep up again. My PSA never went to undetectable. The lowest was 0.04. I was told < 0.02 is undetectable.
thank you for the clarification on AP. Yes, I did have that test during initial diagnostic phase. Now, my Dr puts more into this with scans (ct, bone and PSMA) than PSA number although he still watches that too.
I have been on Lupron 3 month shot since November 2018 with several breaks. It kept my PSA under control until July 2023. Then my cancer became castrate resistance shown by PSA increase while on Lupron and imaging (PET/CT scan). Now, I am on continuous Lupron and Abiraterone 1000mg + Prednisone 5 mg.
I have usual hot flushes, fatigue, and mood swing that comes with ADT. I find these side effects annoying but tolerable. I can live with that as long my cancer is under control.
Now, I have to deal with coronary artery disease with 60% to 70% LAD calcified stenosis. One day I would probably die from heart disease with prostate cancer under control. I try to live one day at a time without health problems taking control of my life.
I may almost be there. I will find out in my next Oncology appointment. The fatigue from the meds (abiraterone) has been substantial. I have gone on disability because of a nerve injury to my leg from an SBRT treatment for a bone lesion on my left femur and the fatigue. I would love to still be working but I found myself falling asleep at my desk and experiencing memory issues. This could literally be a disaster as a professional in building design, so I decided to hang up my shingle.
I don't know that it gets any better but Pluvicto may have less side effects. Good luck and keep us posted.
Thank you for sharing your story. I might be in denial, but still feel I can work, although not at the same pace as before. Memory issues are relatively minor, although more frequent lately. Sleepiness at work is also intermittent. I still feel I can do work, perhaps not as interesting and exciting as years ago, but still enjoyable. Let us know what your oncologist says, And share what you do in your spare time, if you decide to throw the towel. I dread the moment and partially because of that try to keep going.
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