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And they say breast is the worst, I'd argue emphatically its prostate.. especially considering the side effects.
If they enroll the right patients to reveal signal here, they are enrolling patients that I think would be better served by XRT as local therapy.Of course none of us thinks it is wise to offer adjuvant systemic therapy to these patients.
HOWEVER the trials are already running.
There are randomized trials enrolling high-risk postoperative patients (pT3a and GS>7 and R1 or pN1) with undetectable postoperative PSA and randomizing them to ADT+ARSI vs. Surveillance (with the option of salvage RT upon PSA progression). Endpoint is MFS and guess what, salvage RT is not as effective as ADT+ARSI in preventing metastasis in these high-risk patients, many of wno are already micrometastasized,
We are basically screwed, however it will take 5+ years likely, till these trials read out.
Important point: Those trials will pickup MFS/OS benefits if they enroll the right patients.
Our adjuvant/salvage trials enrolled prettx much everyone with a risk factor (you could get randomized in Radicals if you had a GS7 as a sole risk factor!). We did that, because we did not have the money/resources to be selective. Pharma doesn‘t have this problem, they open 500 sites and find the interesting patients with multiple risk factors.
Depending on the endpoint. If the endpoint is PSA progression from local recurrence at the prostatic fossa, then perhaps yes. But many of these patients already carry micronetastatic disease at the point of surgery.If they enroll the right patients to reveal signal here, they are enrolling patients that I think would be better served by XRT as local therapy.
Agreed. Things like this are what makes medicine an art as much as a science. Is more toxicity now worth it to lower the probability of life long systemic therapy later? Is it worth it to prevent or delay the QOL impact of metastatic disease? What do you do with the 82 year old with GG4 disease who is probably not going to have his life extended by local therapy, watch him and then kick yourself if he's miserable at 90 due to bone mets? How do we value the time-value of QOL, like is 6 months of ADT for a sexually active 65 year old may be more impactful then 3 years in an 85 year old with a baseline T of 100? Or is that ageism/projection of our own values?
This will become also more easy, once the oral LHRH antagonists are proven in combination with RT."here's the side effects, and generally speaking, particularly if you're gonna live more than 10 years, here's the benefit of ADT. if you can't manage the ADT after a first injection, we can always stop it and eventually the side effects will fade out most likely back to baseline over months after the end of the duration of effect"
I guess thats one way to do it... Most of my patients are "out of service" anyway, so its really just the misery of hot flashes..
My preferred video(s) regarding bicalutamideAnd as to the other comment: Casodex.. nah. I don't prescribe it (warning, just, well, warning if you don't have a sense of humor anyway).
Follow up article: https://www.nejm.org/doi/full/10.1056/nejmoa1615869I also try to keep in mind the PIVOT trial, namely that half the folks we think have a 10 plus year life expectancy are dead in 5 years
*** May not apply to non-veterans.
Update in 2020Follow up article: https://www.nejm.org/doi/full/10.1056/nejmoa1615869
I guess it is what it is with PSA only low risk disease. But that ain't gonna stop the machines from printing..
I try to avoid projection by discussing during the first visit that we are going to be in a scenario of 'shared decision making' where whatever choice they make between those options above (or say surgery vs RT) they are making the right one for them.
I give the numbers, info, and answer questions. I only tell them what I would do (or want for my family) if they ask.
At the end of the day, I would rather treat things when they are curable with the least amount of therapy. If I thought the 82yo had a chance to hit 92, I'm going RT + ADT up to 18-24 months as tolerated. 3 month Lupron. If he has cardiac history, Relugolix. There is much more to pCA than OS. You can be alive with horrible quality of life due to bone mets.
The second question is more interesting - someone who is UIR needs treatment, IMO, now. If excessively concerned about sexual toxicity, then skip the ADT. Especially if they're 65. They're unlikely to make it to 85 (assuming no treatment) if they do nothing for 20 years with 'just' high-risk disease.
Your payers are approving Relugolix? I have not been so lucky.
As an aside about Relugolix, do you folks believe that 6 months Relugolix = 6 months lupron? Or realistically is 6 months lupron more like 9 months of androgen suppression due to slow recovery? Do we need to re-run the trials? Or does it not matter since castration is more of a threshold so a "recovering" T of 100 might as well be 400?
Very good points. That was my impression too from the ASCO GU abstract.As an aside about Relugolix, do you folks believe that 6 months Relugolix = 6 months lupron? Or realistically is 6 months lupron more like 9 months of androgen suppression due to slow recovery? Do we need to re-run the trials? Or does it not matter since castration is more of a threshold so a "recovering" T of 100 might as well be 400?
Question is whether men are actually compliant with several pills a day... Vs a 3-6 month shot in the officeYour payers are approving Relugolix? I have not been so lucky.
As an aside about Relugolix, do you folks believe that 6 months Relugolix = 6 months lupron? Or realistically is 6 months lupron more like 9 months of androgen suppression due to slow recovery? Do we need to re-run the trials? Or does it not matter since castration is more of a threshold so a "recovering" T of 100 might as well be 400?
Question is whether men are actually compliant with several pills a day... Vs a 3-6 month shot in the office
Your payers are approving Relugolix? I have not been so lucky.
As an aside about Relugolix, do you folks believe that 6 months Relugolix = 6 months lupron? Or realistically is 6 months lupron more like 9 months of androgen suppression due to slow recovery? Do we need to re-run the trials? Or does it not matter since castration is more of a threshold so a "recovering" T of 100 might as well be 400?
We have a rep that comes by. We are getting it approved. I don’t really see the advantage. Why can’t ADT be like it is for birth control where there are literally tons of options? Pills Depo Shots, patches etc
For the bolded - Not 100% of the time, but happy to attempt it in those who are interested in it. It's wild that it, at least seems, like it is better across the board compared to Lupron from the HERO trial, but alas, here we continue with insurance companies driving medical care. Would encourage a man who needs ADT, had relugolix denied by his insurance, and then has a heart attack to then sue his insurance company. Will take a few years though.... anyways, not the point of the post. I recommend it more so in the long term ADTers rather than the patients getting 4-6 months given HERO was about a year of ADT, but all who need ADT are candidate sfor Relugolix.
Second question - I currently treat them as equivalent on timing. I'd rather err on the side of 'lower duration of ADT' as much as I can, but I understand that is not really EBM. I do not think it is worth giving Relugolix longer to 'make up' for the extra length of Lupron effect. I also don't really think it's worth re-running ADT trials when there are better and more interesting things to do in prostate cancer. Maybe a stratification on future large scale trials may be worthwhile.
Fair number of advantages - up to you to decide whether they matter or not. Not really a downside to Relugolix besides its cost.
I remain a bit skeptical about the cardioprotective effects of relugolix. Partly Based on a small number of events over a 1 year period (18 in relugolix group vs 19 in lupron, but relugolix group was 2x the size) and partly due to lack of convincing mechanism. Would love to see confirmatory or long term data.
Certainly I’m happy to use it. But convinced enough to fight insurance for every patient? Not there yet.
Compliance - sure maybe not the best option for those who aren't good about taking daily pills.Fair number of disadvantages. Compliance and cost being two.