Good morning all! I have Gleason nine, stage four prostate cancer, with four known small, skeletal metastases, diagnosed in 2019.
I was on Zytiga and prednisone for 2 1/2 years, with undetectable PSA during that time, down from a high of only four.
I’ve been on a Zytiga holiday, for 10 months now. My hot flashes have been decreasing and my strength and endurance and libido have been coming back gradually. I felt really sick and awful on Zytiga and feel much better now.
Except for one thing… My hands are getting so terribly stiff. Has anyone else had this side effect after going off Zytiga and steroids?
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Sitano1
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Prednisone is a corticosteroid, commonly prescribed for muscle and joint pain. It’s been masking your arthritis. I went on a holiday and had been taking dexamethasone with Zytiga (abi). It had been effectively masking my degenerative osteo arthritis in my hips, which I knew I had, and a bunch in my hands and other joints which apparently developed over the years while on ADT.
Your prednisone is merely a replacement for the cortisol loss caused by the zytiga. Stopping it should be no different than never taking it. I doubt that that the small dose you took could mask arthritis. I've been on vacation for 6 months and my hands are stiffer than they were 6 months ago. I attribute that to being 6 months older. I expect more of that the older I get.
5 mg of prednisone is quite effective in rheumatoid arthritis and it is known that this dose has side effects of diminished immunity, easy bruising, ect. I think 4 mg is closer to exact replacement although there is evidence of side effects down to 2.5 mg in a recent paper. In these patients, however, we are assuming prednisone itself completely suppressed endogenous steroid production and maybe it does not. If it is osteoarthritis the hands will be stiff on the morning but usually loosen up within 30 minutes.
IMO, both he and you have been deceived by MDT into thinking your cancer has been controlled, when, in fact, you have only tampered with your PSA. There are no clinical trials that show iADT+Zytiga is equivalent to cADT+Zytiga. It is a risk both of you are taking without data.
A major clinical trial was not able to say if intermittent ADT was non-inferior to continuous ADT in men with metastases. They found that, with 90% confidence, intermittent ADT, mortality of men using iADT was 10% worse than for men using cADT, but the range (with 90% confidence) was 1% better to 23% worse.
TA, FYI I do not think my cancer has been controlled, just slowed down. I think I am in uncharted territory with this incurable disease, and being incurable no standard treatments have been curative so why not mix it up a bit? I think, being a high risk cardio patient, the holiday could benefit that condition. Also there are many here who have lived well for many years (10+) going on and off ADT. There is no one I’ve encountered on this site with my non-soc treatment history. I have been in uncharted territory for quite a while.
I meant controlled enough to take vacations from systemic treatment without harm. "so why not mix it up a bit?" - You are certainly free to take whatever risk you want with your body and your life. But it is a risk. "Also there are many here who have lived well for many years (10+) going on and off ADT." And many have died, so they aren't on here. That's why patients should not make decisions based on anecdotes. That's why the iADT trial is cautionary - more patients (all with their own anecdotes) did worse than did better with iADT.
”Also there are many here who have lived well for many years (10+) going on and off ADT. ”
There is a very prevalent confirmation bias in this group about longevity… supported with statements like yours.
The problem with that is that yes, there may be many here who’ve outlived the models/expectancy, but all those who haven’t aren’t here to post things like “I died at 4 years” to offset the bias.
Personally I cringe every time I read something about “the statistics are wrong because I’m still here…”. You guys who post that are the lucky ones, the unlucky ones aren’t here posting.
????!! I don’t see your point. I don’t believe the statistics are wrong. Each of our stage IV mPCa are very unique. No one size fits all. I’m navigating my own situation as I think appropriate. I was given 18 months to live by my urologist who did my prostate biopsy. I’m very thankfull I’m going on 5 years now asymptomatic. Why do you think I’m saying “the statistics are wrong”?
Hey how did I get in the middle of this lol. I understand there’s risk to IADT. You are 100% wrong however to say I’ve been “deceived by MDT into thinking your cancer has been controlled..”. I get that MDT may or may not benefit my longevity and it clearly by itself doesn’t control my cancer. Dr. Scholz and Dr. Lam however, do not believe my IADT will significantly shorten my life span over CADT. . They may be wrong. Like you say there’s no trial comparing IADT plus Zytega to CADT plus Zytega. Therefore even you must admit IADT plus Zytega could be found to extend survival over CADT .
I do trust Scholz and Lam tho. They were right to give me the triplet therapy at my first sign of metastasis……long before that became standard of care and was proven to extend survival greatly. They also helped me to use Provenge while still castrate sensitive. My point is I’m making my decisions with my eyes wide open. You’ve been incredibly helpful making those decisions with your vast array of information TA. For that I thank you profusely. But I do find it insulting to insinuate my decisions are based upon being “deceived”. Nothing I’ve said in our private conversations or my public comments here can be found to show that to be true.
You are using PSA to make your decision about a vacation. That is the deception, as I said. You have treated PSA by using MDT on the visible metastases. Then you are using PSA to decide when to end your vacation. It is circular reasoning. I'm not saying it doesn't work. I'm saying there is no evidence. I actually encourage MDT as long as its used together with systemic therapy. We know systemic therapy works. We do not know if there is any benefit to MDT. You are forgoing systemic therapy because you are deceiving yourself by relying on PSA that your cancer is controlled. I have no idea why you find that truth insulting.
BTW- you did not get triplet therapy the way it was proved to work, de novo, that is.
Hey T/A, are you saying we are relying too much on just PSA values versus PSA and scans while on vacation? I went off “the shot” one year and three months ago and off Zytiga six months ago after being on both for three years. I just had my scans in November and still all clear. So I guess my question is while on vacation, how often should I have scans provided my PSA remains undetectable? I’m still getting my PSA checked every three months.
" We do not know if there is any benefit to MDT ". I assume you mean radiation to bone spots? If so, I disagree--this is valuable therapy as it's important to save bones from tumors so we don't become crippled, especially the spine.
Yes, there is certainly relief from bone deterioration and pain, but some use MDT to oligometastases as a way of slowing progression, which is what I was responding to in 6357axbz's post.
interesting reasoning TA. But I still think it’s flawed. I understand that the unknown long term impact of MDT is still not fully understood. Here is what actually happened in my case. At my first sign of metastasis about 4 years ago, I did do MDT to my three mets. However, I also did the triplet therapy at around the same time. I continued the triplet therapy for about 30 months. My PSA was .02 for the last 24 months of that systemic therapy. Then I began vacation # 1.
Are you suggesting that perhaps my PSA was still undetectable some 2.5 years after MDT solely because of the MDT and I was fooled into thinking the systemic treatment was working better than it actually was? I am pretty certain my PSA was undetectable that long primarily because of the systemic triplet therapy and that I wasn’t being “deceived” into thinking that thinking. If in fact MDT alone can keep your PSA undetectable for two and a half years, it may be more effective than we think
Now, vacation two was after only a year of Lupron and Zytega. But I only had one very small met that had MDT. I doubt that MDT to that one met would lower me to undetectable PSA for over a year. Again I’m pretty certain it was the systemic treatment and that I wasn’t fooled into that thinking.
Finally, I’m confused by your last comment that my triplet therapy wasn’t at “de novo”. It was done right after I was diagnosed with the three metastasis. Isn’t that de novo? Or is de novo only for men first diagnosed at all with PC and they are already in stage 4?
As always I appreciate and respect your thoughtful response
(1) It may help you understand what is going on if you took some time to understand exponential curves. Such curves are prevalent in biology -growth of cells, bacteria, viruses, cancer, spread of disease, etc. I made up one to illustrate (data are not real). As you can see, very few metastases in early years are detectable, and new ones become detectable only very slowly. If you use a more sensitive detector (like a PSMA PET scan) you shift your position on the curve to the left, but you are still riding the same curve (this is called "lead-time bias").
I stress "detectable" because there are thousands of metastatic cells systemically (all over one's body), but only a few are large enough to be detectable. Even the most sensitive PET scan cannot detect tumors smaller than 4 mm. Remember, each tumor is also going through exponential growth - very slow at first.
(2) In men who are PSA-recurrent after prostatectomy, it takes a median of 8 years for the first metastasis to become detectable. After that, I've seen that more than a year can go by between the detection of the first metastasis and the next one. Some researchers, who should know better, observed that in their patients who had early metastases treated with radiation, new metastases did not occur for a long time. They attributed the delay to the treatment rather than the natural history of metastatic progression It is impossible to know if there was a delay in progression without a randomized clinical trial.
What is really happening during this extended time period? The accepted theory is called "seed and soil." There are millions of cancer "seeds" in the serum, the lymph, around nerves, and hiding in various tissue reservoirs (mainly in bone tissue). While they appear to be quiescent, they are in fact changing the "microenvironment" of the tissue they are in. They are transforming the tissue to make it more conducive to prostate cancer growth, building networks of collagen, fat, blood vessels and nerves, influencing healthy cells to become cancerous, and preventing the immune system from destroying the new nests.
Because it takes such a long time to build up the metastases to the point that they are detectable by even our most sensitive PET/CT scan (the tumor detection limit is about 4 mm - millions of cells), it seems that there is little there and even less going on. This is called "oligometastatic" cancer. It seems like all the cancer can be picked off by playing whack-a-mole -- zapping the few detected metastases with intense radiation (called SBRT) as they are detected. In fact, it is well-established that SBRT provides excellent "local control." "Local control" means that the metastases are usually completely annihilated by just one or two "zaps". Because the detected metastases are the source of almost all the PSA, PSA can fall to undetectable levels after such treatment of oligometastases. But the cancer is far from cured - the PSA has been treated, but the cancer is still micrometastatic and systemic.
(3) This is why I can only shake my head when you make such statements as, "If in fact MDT alone can keep your PSA undetectable for two and a half years, it may be more effective than we think" and "I doubt that MDT to that one met would lower me to undetectable PSA for over a year. Again I’m pretty certain it was the systemic treatment and that I wasn’t fooled into that thinking."
You have made the mistake of thinking that treating PSA is equivalent to treating your cancer. All of your PSA comes from the tumors that have grown large enough to generate their own blood supply. No blood supply, no PSA. So if you eliminate the metastases that have their own (leaky) blood supply, you eliminate PSA.
Chemo, hormonals, immunotherapies, and radiologicals eliminate many metastases systemically, but not all of them, unfortunately (unless the cancer is still locoregional). The most resistant ones will always grow and spread exponentially.
EXTEND is a Phase II randomized basket trial for multiple solid tumors testing whether the addition of MDT improves PFS for patients with oligometastatic cancer. PFS was prespecified to be independently assessed and reported at 41 progression events, which occurred after a median follow-up of 22.1 months. “This study shows that the combination of metastasis-directed radiation and intermittent hormone therapy significantly improved progression free-survival, with manageable toxicities, for patients with oligometastatic disease,” Tang said. “I am encouraged that this data, combined with knowledge gained in future trials, will allow us to safely preserve a man’s quality of life following this diagnosis.”
I don’t recall the trial but I remember a positive correlation between PFS and OS.
That is circular reasoning. PFS is predominantly PSA. So they proved that by treating PSA, they can lower PSA.
When they treat PSA, they cannot use a PSA-based endpoint. They can only use the appearance of new metastases or overall survival. There are several trials that attempt to measure that, which we will have in a few years.
Schwah, I’m guilty of getting you into this discussion. TA made the comment, “I've never heard of someone "on holiday" from Zytiga”. I reminded him that he was aware of at least two people that were on holiday from Zytiga. You and I. My apologies for dropping your name.
You didn’t say the statistics are wrong, but you did say ‘many’ men here have lived well for 10+ years off and on ADT. It’s a statement that can seem comforting, but it also can mislead those looking to vacations for relief that for ‘many’ either have no effect or don’t last long enough make much of a difference before having to return to ADT.
Hopefully you are improving your cardiovascular fitness to benefit the cardio issues and not looking to drug holidays to do the job, which is far less effective.
I switched from trelstar to 3 estradiol patches , .1mg per week in Feb2019 to reduce the cardio and orthopedic side effects of SOC ADT. (Prior to that I was on iADT which was ineffective. )
This past March I added Xtandi, 80 mg as psa started to rise. It’s been undetectable since. I’m Gleason 9 with oligomets in bones in the past. Going on 10 years since diagnosis.
Wow...a very good thread. Sorry I am getting in so late.
I have been on ADT (Lupron/Zytiga) for 2.5 years. CT/Bone scan did not show any definite metastasis. PSMA PET showed "possible" metastasis in 4 spots around ribs. "Indeterminate" was the radiologist's wording. I had Gleason 8/9 with a PSA of only 1.89 (on Finasteride). Treated aggressively due to possible Stage 4. PSA and testosterone immeasurable currently. Had 25 rounds radiation of prostate of primary tumor last year.
I've been recently consulting with MSK as a 2nd opinion. They usually allow ADT "vacations". However, they are saying that there was no definitive determination that I have any metastasis. But before going off ADT, they recommended radiation of the pelvis and lymph nodes (as one was enlarged). I just started 25 rounds of radiation to the pelvic region in hopes for a cure.
Questions:
1. What PSA limit should I go back on ADT if I am not cured?
2. If the PSA starts sky-rocketing, how quickly do I need to act to get back on ADT? I'll be getting testosterone/PSA tests every month as I have been doing to keep on top of it.
3. PSA will go up anyway to some low level even if no metastasis. Any idea what level that could be?
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