ASCO GI & ASCO GU

[sirspamalot]

And they say breast is the worst, I'd argue emphatically its prostate.. especially considering the side effects.

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[DoctwoB]

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?

 

[sirspamalot]

Ask the patient, hope they can parse and come to a rational decision. Sometimes, there is no right answer.

 

[Palex80]

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.

 

[communitydoc13]

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.

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.

We will see how surgery impacts low volume metastatic disease soon enough. I am biased of course, but sx has yet to demonstrate the same synergy with ADT as XRT.

 

[Palex80]

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.

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.

Also bear in mind, that the trials will be designed in a way to maximize the chance that micrometastatic patients enter. They will not ask for PSMA-PET staging fpr instance, merely a negative CT and bone scan.

 

[evilbooyaa]

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?

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.

 

[sirspamalot]

"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..

 

[DoctwoB]

I 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.

 

[Palex80]

"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..

This will become also more easy, once the oral LHRH antagonists are proven in combination with RT.

 

[sirspamalot]

I think we could probably take any group of sick-ish people, and do a PIVOT like trial and basically show minimal impact.

And 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).

 

[medgator]

And 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).

My preferred video(s) regarding bicalutamide

 

[sirspamalot]

My preferred video(s) regarding bicalutamide

 

[sirspamalot]

I 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.

Follow 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..

 

[Chartreuse Wombat]

Follow 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..

Update in 2020

Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)

Very long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain.To determine long-term effects of surg…

www.sciencedirect.com

 

[DoctwoB]

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?

 

[NotMattSpraker]

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?

Ive had a mix, but when it is not the company has helped work with our specialty pharmacy to cover the medication.

ADT is so squishy I dont think repeat trials would add a lot to recommendations.

 

[Palex80]

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.

 

[sirspamalot]

You think breast is the worst? Look at the voting record from these guys on the other side of the water.

Honestly, if anyone knows what the "right" thing to do for any given UIR or HR patient is.. depending on the PSMA PET... they're blowing smoke.

I once again declare prostate to be the worst. But boy oh boy does it generate that cash.

 

[medgator]

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?

Question is whether men are actually compliant with several pills a day... Vs a 3-6 month shot in the office

 

[Fpg1245]

Question is whether men are actually compliant with several pills a day... Vs a 3-6 month shot in the office

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

 

[evilbooyaa]

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?

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.

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

Fair number of advantages - up to you to decide whether they matter or not. Not really a downside to Relugolix besides its cost.

 

[Fpg1245]

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.

Fair number of disadvantages. Compliance and cost being two.

 

[DoctwoB]

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.

 

[IonsAreOurFuture]

It's purely anecdote, but my patients on 6 months relugolix seem to be able to return to sexual function whereas the 6 month depot patients don't.

 

[evilbooyaa]

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.

Sure, can await future f/u data, but comparing gross numbers when Relugolix group had twice as many patients seems a little backwards. Guess it's early vs late adopter.

Previous GNRH antagonist (Degarelix) has shown similar reductions in heart issues compared to multiple other GnRH Agonists: Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice

There's a lot of information in the discussion that I won't pretend to be an expert on but explains why Agonists seem to be worse than antagonists

Fair number of disadvantages. Compliance and cost being two.

Compliance - sure maybe not the best option for those who aren't good about taking daily pills.

Cost - depends - if its covered, then it's usually not that bad. Obviously the fact it's not fully covered is more of the issue. But, it's a one time attempt from my end with counseling patient about potentially prohibitive cost - if they check back in at following OTV and say it went fine, then cool. If it didn't, then Lupron it is.