I suspect that you are right that they are trying to hit the cancer as hard as they can with a souped up adjuvant hormone therapy. Given the impressive survival benefit for mHSPC, and the recent discovery of benefit in non-metastatic PSA-recurrent patients using it as part of an intermittent ADT protocol (below), there is every reason to believe it is beneficial in high risk patients receiving RT as well.
MSK is the lead investigator of the AASUR trial, which gives Zytiga and Erleada to very high risk men receiving RT. The results are expected in May, but they may already be aware of a benefit;
Great, let us know what he says. I think there is no right answer, because we had ADT + Z adjunctive to Brachy, which is exclusionary to the major trials. Thus, statistically speaking, we can't really infer anything from them.
No, I didn't say they did. But they do suggest a benefit to adjuvant abiraterone when used earlier. Given that the OP feels good and was somehow able to obtain adjuvant abiraterone, why would he forgo that opportunity? As I said, the doctors at MSK will have access to the most relevant data.
He might forego that opportunity to use Zytiga now, and save it for later if he had an unfortunate recurrence, which is the population studied in link #1.
There's really no hard, statistically relevant data on folks that have had prior Brachy, because all the major trials exclude it.
I definitely do not subscribe to the philosophy of "save it for later." He is attempting a curative therapy, not something that he knows now will have to be treated later. Resistance evolves more slowly when used earlier. God willing, he will never need another therapy if this one kills off all the cancer cells. If it doesn't work, later, there will be other other therapies.
The reason the trial excludes brachy boost therapy is because they hope that by going heavy on the adjuvant hormone therapy, they can prevent the relatively high level of late-term urinary toxicity caused by the boost. Maybe he doesn't need the extra Zytiga, but if he is feeling great, why would he not take it?
Rhetorically: If Westof is M0 and in primary tx, why bank a decision to use Zytiga on studies that were done either for recurrent patients or studies on M1 metastatic patients like CHAARTED that support the kitchen sink approach? The OS benefit cited applies to those groups. He doesn't fit either one.
Are there any studies that show Zytiga adds to OS for M0 patients as primary tx?
Because, with no data, we still have to make treatment decisions. If we see a trend in greater benefit when used earlier, it is reasonable to suppose the trend will continue. No evidence of benefit is not the same as evidence of no benefit. Of course it may be wrong, but for now, that is the best guess.
I have been trying to sort out “hitting it hard” vs treatment related emergent resistance.
Seems there are two related phenomenon I have read via our groups discussions.
1. The lower Gleason Pca cells are in some balance with the higher Gleason Pca cells.
2. Pca is a dynamic system and will adapt, presumably via mutation, to treatment pressure and become resistant to that pressure.
I remember discussions that intermittent treatment doesn’t result in improved results. However, the paper on “evolutionary “ designed intermittent therapy seemingly solves this problem by applying the treatment to knock PSA back to original levels and the stopping and constantly repeat this “mowing of the grass” strategy, forestalling treatment resistance and not killing off the weaker Gleasons to retain the weak/ strong balance.
I understand in this case the strategy is hopefully curative, thereby ending the problem. Does this all imply a probability risk/reward assessment in deciding whether to use this strategy.
You say “resistance evolves more slowly when used early”. Did I misunderstand the above resistance mechanisms - how does this slow resistance emergence fit?
Given the above, is treatment resistance also proportional to drug dosage?
You have to be careful about information you think you are getting from discussions on this site- there is a LOT of misinformation here and I don't have time to review it all.
(1) It has nothing to do with Gleason score.
(2)Cancer cells do adapt to selection pressure BUT that is not the only reason they become castration resistant
(3) Every indication is telling us that early reduction of the NUMBER of clones has a greater effect than selection pressure.
(4) Castration resistance takes exactly the same time to appear with Intermittent ADT as with continuous ADT
I was using hi /low Gleason as shorthand for a more or less aggressive Pca cell — but I guess the idea that in a tumor the low aggressive Pca cells have some form of controlling/balancing influence on hi aggressive Pca cells is an invalid concept
You're doing great AJ, glad you worked out the insurance with the help of your supportive wife. I'm also benefiting from my wife's insurance as I'm a retired CPA and she is a medical researcher. Anyway, best of luck with your upcoming appointment, will be interesting to see what they say.
I was offered this trail about 2 years ago at MSK and declined to receive it. I am not sure if I did the right thing on not based on what TA has said above.
Westof: that's the the million-$ question I'm trying to figure out, i.e. whether to restart Zytiga after dropping it in August due to high BP midway through IMRT.
I discussed this with my local Uro, who prescribes to the thought that Zytiga adds to OS. I mentioned to him that the trials supporting ADT + Z didn't really apply to me as T3N1M0 +SV on several counts, (1) the big one is that prior Brachy tx is exclusionary for all these trials (because Brachy could be curative ex-ante), and (2) the trials were top-heavy with G> 8, M1 metastatic participants. He sort of nodded to all of these, but said the trials still were suggestive that Zytiga adds to OS even in nmHSPC. Added to the above is the 2018 Aagarwal study showing Zytiga is associated with a risk of "treatment-emergent" small-cell NE PCa in mCRPC, which poses the question, does it pose the same risk for nmHSPC?
So, I've pretty much decided not to risk going back on Zytiga-- I don't like the added toxicity of high BP when I've had heart palpitations in the past. I will discuss with my MO in March, and get some more feedback then. Meanwhile, it's eight more months of Lupron which seems to be doing the job, as my PSA continued to drop from 0.03 in August when I dropped Zytiga, to <0.01 now.
By bp went up and I hit with meds then it moved up so I doubled it and I’m back to 120/70. I’m glad I’m going off the Zytiga soon. I’m tired.
In the non-metastatic setting, prostate cancer that is considered high-risk and meeting 2/3 criteria: T3 or T4 primary (yours was T3 by MRI), PSA >40 (yours 25), Gleason 8 or higher (your 9),
Qualify and live longer when treated with zytiga and radiation/leuprolide per Stampede trial.
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