Good video for those interested in Salvage Radiation

[GeorgeGlass]

I got this share from someone, Tallallen maybe. It is recent and based on the Oriole study. Thought some of you might be interested if you think you are Oligometastatic. urotoday.com/video-lectures...

[Fanger1]

Thank you for the video link.

[GeorgeGlass in reply to Fanger1]

you're welcome Fanger.

[Tall_Allen]

Here's an article about the ORIOLE trial. It really didn't show much of anything - only 6 months of follow-up.

prostatecancer.news/2019/09...

[GeorgeGlass in reply to Tall_Allen]

in the video they referenced it and said there were differences between those who were radiated and those who weren't. I just read through the prostatecancernews articles. Sounds promising for those that can treat all of their tumors. More of an effect other than just lowering psa temporarily.

[Tall_Allen in reply to GeorgeGlass]

Well, what it actually showed was that PSA was reduced for 6 months following MDT. It's called "treating PSA." Maybe there is a real benefit, but that study doesn't make that claim.. It's a common misinterpretation. You can read about here:

prostatecancer.news/2020/07...

[GeorgeGlass in reply to Tall_Allen]

It may be a little early to know for sure but these doctors are aware of the temporary PSA effect and are saying, " the strong T-cell response found by this study suggests that there may be a true delay in progression and not only a delay in PSA. Also, the fact that distant metastases were delayed by almost 2 years among those who had all of their PSMA-detected metastases irradiated, suggests a true response." Thus, a suggestion or anecdotal evidence isn't proof, but there appears to be a decent chance that it has a greater effect than just psa.

[Tall_Allen in reply to GeorgeGlass]

A T-cell response is certainly encouraging, but most immunotherapies (like Keytruda, Prostvac, and several other immunotherapies) do elicit an initial T-cell response but have been proven to have no effect on survival. In fact, there is a synergy between MDT (not necessarily oligometastatic) and immunotherapy that may be absent when either is used alone:

prostatecancer.news/2016/08...

I think that quote misinterprets the data. Dr Tran's discovery that distant metastases were not delayed when there were more metastases discovered via PSMA PET/CT puts a necessary limit on any possible benefit: only those men with oligomets discovered via PSMA PET/CT may benefit, if there is a benefit. It does not show a benefit - there would have to be a randomized comparison (to patients with oligomets discovered by PSMA PET/CT but not treated with MDT) for that. See the difference?

[GeorgeGlass in reply to Tall_Allen]

Ya, I understand what you are saying. It's hard to make a definitive benefit statement without a control measure or something to compare it to. How would one know if they are happy if they don't know what it's like to be sad. MDT synergy is definitely promising but it's hard enough to get one specialty doc to pick up the phone and call the other. I'd love to know if there are any good hospital treatment centers who are particularly good at combining therapies and teamwork amongst radiation, medical, urology, immunology etc. Many places say they are good at this but they aren't nearly as good at it as they think they are.

[GeorgeGlass in reply to Tall_Allen]

Another question would be, what are the negatives for those that get this radiation treatment?

[Tall_Allen in reply to GeorgeGlass]

The negatives are these:

(1) safety - it is not safe to direct radiation to the mediastinum, or if detected metastases are too close to enteric tissue.

(2) withholding of systemic therapy - we know that systemic therapies (ADT with chemo or second-line hormonals) have a significant proven benefit in men who are metastatic and hormone-sensitive. Withholding those therapies just because PSA has been treated is dangerous.

If a man is oligometastatic and is using adequate systemic therapy, and MDT of his oligomets is safe, I think it is a good idea to have them zapped. If nothing else, there may be a placebo effect by doing something about the more obvious sites of cancer. I don't kid myself that there is as yet any convincing known benefit. In several years, we will have a better answer from Phase 3 RCTs. Meanwhile, what is the harm of hedging one's bets?

[GeorgeGlass in reply to Tall_Allen]

Good points. My MO at Duke likes the idea of saving bullets in his belt and prefers to provide higher quality of life now, with less side effects. Maybe he's worried about my coronary artery plaque 30-40% in some areas. But to your point, if I added Nubeqa now with the ADT, I might get a couple years more total ADT effectiveness, with increased side effects....but nobody knows how light or bad the side effects would be. Maybe they wouldn't be that bad for me. You are definitely an advocate of using mass on the enemy all at once instead of firing a couple rifle shots per hour. There is no overwhelming impact on the cancer. I've seen some of the study results supporting the Zytiga and or Xtandi added to ADT early provides greater lifespan. One might argue though, that if the zytiga makes a guy sit on the couch all day and never exercise, then his bones get weak and he is in a wheelchair after 4 years, that all that might not be as good as someone on ADT alone who is going to the gym daily and having some fun and a good bone structure. That seems like a hard thing to compare. What do you think?

[Tall_Allen in reply to GeorgeGlass]

That is exactly why randomized comparison trials like STAMPEDE or LATITUDE are so valuable. When there are 2,000 men randomized to ADT+Zytiga or ADT alone, odds are that there are roughly equal numbers of inherent couch potatoes in the treatment and control groups. If ADT + Zytiga caused more men to become couch potatoes (compared to ADT alone) and that behavior caused more CV issues, then their decreased survival would be seen. But the opposite was seen - they lived longer, much longer.

It is a mistake to think that QOL is maintained better by long-term ADT vs the intensified therapy. What actually happens is that pain and organ function decline more rapidly when intensified therapy is not used. Contrary to your hypothesis, quality of life was not decreased by the intensified therapy. For apalutamide, for example:

urotoday.com/conference-hig...

[GeorgeGlass in reply to Tall_Allen]

Thats good information. So, do you think Erleada would be the most logical drug to add first for adt sensitive people, or Nubeqa?

[Tall_Allen in reply to GeorgeGlass]

There's never been a comparative study. Nubeqa doesn't activate GABAA, so it may cause less fatigue. So far, it is only approved for non-metastatic CRPC.

[GeorgeGlass in reply to Tall_Allen]

why wouldn't they approve it for metastatic? I guess they can give it to me because they dont have any soc evidence of metastasis. whats better, nubeqa or erleada?

[Tall_Allen in reply to GeorgeGlass]

Because they only have test results so far for non-metastatic CRPC. There are no comparative studies.

[GeorgeGlass in reply to Tall_Allen]

this is a pretty good article. I might ask my doctor if I can add Erleada and then if I have trouble with adverse effects I could switch to Nubeqa. fiercepharma.com/pharma/cha...

[GeorgeGlass in reply to Tall_Allen]

I don't know how I missed this info two years ago. The adverse reactions look pretty low except for rash and hypothyroidism:

What does the % mean when they show a % and then a decimal? I presume the second % is the percentage of all the people who took the erleada. Is that correct? If so, then what does the first % (not in parenthesis) describe?

ADVERSE REACTIONS

Adverse Reactions — The most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.

Laboratory Abnormalities — All Grades (Grade 3-4)

Hematology — anemia ERLEADA™ 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA™ 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA™ 41% (2%), placebo 21% (2%)

Chemistry — hypercholesterolemia ERLEADA™ 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA™ 70% (2%), placebo 59% (1%); hypertriglyceridemia ERLEADA™ 67% (2%), placebo 49% (0.8%); hyperkalemia ERLEADA™ 32% (2%), placebo 22% (0.5%)

Rash — Rash was most commonly described as macular or maculo-papular. Adverse reactions were 24% with ERLEADA™ versus 6% with placebo. Grade 3 rashes (defined as covering > 30% body surface area [BSA]) were reported with ERLEADA™ treatment (5%) versus placebo (0.3%).

The onset of rash occurred at a median of 82 days. Rash resolved in 81% of patients within a median of 60 days (range: 2 to 709 days) from onset of rash. Four percent of patients treated with ERLEADA™ received systemic corticosteroids. Rash recurred in approximately half of patients who were re-challenged with ERLEADA™.

Hypothyroidism was reported for 8% of patients treated with ERLEADA™ and 2% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA™ and 7% of patients treated with placebo. The median onset was day 113. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted.

[Tall_Allen in reply to GeorgeGlass]

The first number is the percent of patients who had any grade (1-4) toxicity. The second number is the percent of patients who had serious or life-threatening (Grade 3 or 4) toxicity. It's easier to read if you look at page 3 of the prescribing info:

janssenlabels.com/package-i...

[GeorgeGlass in reply to Tall_Allen]

I'm concerned about these figures because I have very low HDL and 30-40% blockage in my coronary arteries so I certainly would not want high ldl, triglycerides, and blood sugar. Laboratory Abnormalities — All Grades (Grade 3-4)

Hematology — anemia ERLEADA™ 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA™ 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA™ 41% (2%), placebo 21% (2%)

Chemistry — hypercholesterolemia ERLEADA™ 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA™ 70% (2%), placebo 59% (1%); hypertriglyceridemia ERLEADA™ 67% (2%), placebo 49% (0.8%); hyperkalemia ERLEADA™ 32% (2%), placebo 22% (0.5%)

The overall PSA progression free survival difference was 68% vs. 47.5% so that is a decent amount of difference, so it might be worth it to try and see how it affects my chemistry and hematology. If it screwed me up, I could just stop taking it.

[jimk_mb in reply to Tall_Allen]

Thanks for this post TA. I am will be starting Zytiga in the next couple of days and this info gives me a little better feeling about taking it. I will look up those 2 trials.

[Tall_Allen in reply to jimk_mb]

They will be doing a trial of Zytiga ± a PARP inhibitor at COH that may be of interest

clinicaltrials.gov/ct2/show...

[jimk_mb in reply to Tall_Allen]

Appreciate it, will discuss with Dr. Lam at next visit.

[Tall_Allen in reply to GeorgeGlass]

It was 6 months of follow up, so how can you possibly glean from that that there was anything more than a temporary effect on PSA?