ASTRO Congress News

[Mandelin Rain]

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Scar, honest question.... where in the patient's body do you think the post-R0 resection PSA of 1.0 and subsequent rise to 2.0 is coming from? Where are the cells producing this PSA? Urologist did a hemi-prostatectomy? Pathologist missed a large involved margin? 2 consecutive lab errors?

Looking at the most recent Stephenson update, if you gave this guy XRT alone, he'd have a 10-year control rate of about 15% without factoring in a PSA DT of 1 month at all. I think that's pretty accurate, though I'd be slightly more pessimistic. Worth treating? Sure, I'd treat the guy if he wanted to be AGGRESSIVE. Worth calling it a big mistake to treat him with ADT alone? Not sure I'd go that far. He got both opinions. He went with the ADT.

 

[scarbrtj]

Scar, honest question.... where in the patient's body do you think the post-R0 resection PSA of 1.0 and subsequent rise to 2.0 is coming from? Where are the cells producing this PSA? Urologist did a hemi-prostatectomy? Pathologist missed a large involved margin? 2 consecutive lab errors?

On of the best medical philosophies I know of is here and came from a guy who's obviously not a doctor. That said, you asked for my opinion, and here's my opinion in order of likelihood re: the source for the R0 PSA(s) here.
1) He only had two nodes dissected.
2) He could have a positive margin. Pathologists are human.
3) PSA testing, at least in the scenario here where the mean PSA is 1.5 based on two values of 1 and 2, is a bit of a black box.
4) He could have extrapelvic disease.
#1-3: Pascal's wager again.
EDIT: I once had a patient with a PSA of something like 5 or 6 after "R0" prostatectomy. All imaging negative. Long story short, I get planning MRI on all postop and intact prostate patients. I discovered significant amount of what looked like seminal vesicles on the MRI which I couldn't really believe but hard to ignore. After a lot of detective work on my part, discovered the (academic) urologist had decided to leave the seminal vesicles in during that particular case on that particular day.

 

[medgator]

, discovered the (academic) urologist had decided to leave the seminal vesicles in during that particular case on that particular day.

Happens more often than anyone likes to admit.

After being out in practice for several years, I'm shocked at how much sv tissue I can see on a planning CT let alone MRI in post RP patients

 

[Mandelin Rain]

Shouldn't cause a PSA of 5-6

 

[scarbrtj]

Shouldn't cause a PSA of 5-6

There are so many things that go into a "shouldn't." Remember that episode of House where the woman asked him, "Sitting on a toilet seat shouldn't get you pregnant, right?" And House said, "If there were a man between you and the toilet seat, it could."

 

[Palex80]

Stampede included high risk non metastatic pts

Not the same scenario.
They included non-metastatic patients WITH an intact prostate.
They did not include post-operative "PSA-rise-only" patients without macroscopic metastasis, unless they had very high PSA-values (PSA > 20 ng/ml).

These patients should not get ADT + Xtandi. It's not indicated, not with the evidence we have nowadays.

You could advocare to give him ADT alone and wait until PSA rises again. Then perform imaging and (most probably) not find anything again, in which cases he would be castration resistant non-metastatic prostate cancer and thus eligible for Enzalutamide, Apalitamide or Daralutamide.

 

[Palex80]

Well, see, he had a PSA rise of 1 point, from 1 to 2. That means he has metastatic disease. It’s really unfortunate. If only his docs had “believed” the initial PSA of 1 and not repeated it a month later. Reminds me of those people whose birthdays are Dec 31st and who say “If I’d been born one day later I’d be a whole year younger.”

I also think that he most probably has micro-metastatic disease, but that's not the group of patients the trials were run with.
It's simply not the same. He needs to have macrometastatic disease or a high PSA to be eligible for escalation of systemic treatment beyond ADT.

Almost any patient with a Gleason Score 5+5=10 and a pT3a/b has micro-metastatic disease too. Do we ommit adjuvant/salvage radiation therapy in all of them, because they most probably have micro-metastatic disease? Do we treat all of them with ADT and Chemo / Abiraterone in the postoperative setting with low PSA and non-detectable macroscopic metastases? Nope.
Why? Because (here as well) there is no evidence for that.

 

[scarbrtj]

Shouldn't cause a PSA of 5-6

Btw hadn’t realized you were citing me a paper here. The rest of the story is had another urologist TRUS bx what “SV” he could see, against his skepticism that it would be positive. It was positive. Anecdotes!

 

[thesauce]

I love this debate and the thought you guys have put into it

I will reiterate once again that evidence-based medicine is not intuitive. The question I had was whether salvage RT would be beneficial, not whether or not patient has micrometastatic disease.

This case of a patient with a fast PSA DT has been shown to receive perhaps the most benefit from salvage RT. The data is more compelling for it for this factor than with a positive margin (and no one would argue giving RT in the setting of a positive margin). I don’t know why this benefit would be seen in the setting of micromets, but that’s just the way it is.

If all we had to do was what makes sense, this job would be way easier. You wouldn’t have to run expensive trails or publish studies, you wouldn’t have to read them, and we wouldn’t need a decade of medical training.

 

[Mandelin Rain]

I love this debate and the thought you guys have put into it

I will reiterate once again that evidence-based medicine is not intuitive. The question I had was whether salvage RT would be beneficial, not whether or not patient has micrometastatic disease.

This case of a patient with a fast PSA DT has been shown to receive perhaps the most benefit from salvage RT. The data is more compelling for it for this factor than with a positive margin (and no one would argue giving RT in the setting of a positive margin). I don’t know why this benefit would be seen in the setting of micromets, but that’s just the way it is.

If all we had to do was what makes sense, this job would be way easier. You wouldn’t have to run expensive trails or publish studies, you wouldn’t have to read them, and we wouldn’t need a decade of medical training.

I didn't pull up the whole paper that was cited earlier in this thread in reference to PSA DT. However, I do know that that paper compared No Salvage to XRT with or without ADT. My guess is that the rapid doubling time patients were more likely to have ADT added to XRT than slow PSADT patients and also the typical retrospective study caveats that the guys who received No Salvage were likely sicker/co-morbid/old/whatever. It did not compare XRT+/- ADT to ADT alone.

Without reading the whole manuscript, I can't guarantee this is the case, but I'm guessing it is.

I definitively wouldn't advocate No Salvage for your patient and I likely would have recommended exactly as you did, while doing my best to temper expectations.

 

[deleted1002574]

I know it’s apples to oranges, but we very easily offer RT/Chemo to GBM for minute chance of cute... without hesitation, people give 6 weeks for RT ... to the brain ... for patients with median survivals of 9-20 months.

Attempt salvage. Understand it probably won’t work.

 

[evilbooyaa]

I know it’s apples to oranges, but we very easily offer RT/Chemo to GBM for minute chance of cute... without hesitation, people give 6 weeks for RT ... to the brain ... for patients with median survivals of 9-20 months.

Attempt salvage. Understand it probably won’t work.

Bingo. People want to talk about the 'futility' or prostate RT then go 60/30 a biopsy only MGMT-non methylated GBM.

The argument is that there is a survival advantage of the RT in GBM which isn't known in this prostate population.

To reiterate - this patient should be given salvage RT but his risk for metastatic failure is high.

 

[westcoastonc]

Sounds like Frosty is intimidated by Spratt or has some personal beef. Weird, as I met Spratt on a rotation and he is really nice. The residents love him.

Nguyen said Spratt’s study was super strong and that he himself will think hard before giving ADT reflexively.

The whole point of Spratt’s talk was that PSA is a predictive biomarker. Nguyen confirmed all the harms of ADT. Great interview on quadshot.

I went to ASTRO this year and thought it was one of the most important talks and guidelines are going to change I am told to better enforce shared decision making, and given RAVES data.

Spratt showed the credibility criteria even and Nguyen agreed it was a very robust secondary analysis.

Considering the author line is comprised of most of the nations prostate experts I think it was an NRG team effort that Spratt was the 1st author of. Criticism is being made to most of the GU experts like Sandler and Shipley.

I bet if Frosty messaged him on twitter he would happily discuss as he seems to respond to everyone. I messaged him about jobs and he helped out.

I wouldn't believe Spratt over Nguyen. I have no affiliation with either of their centers, but one of those two talks with his emotions on his sleeve, guns ablaze; and the other is a kind, mild-mannered person. I know which one of them is prone to distort his viewpoint.

BTW, your post-hoc analysis argument would also mean that we may have had to stop giving TNBC hypofrac after results of the Whelan trial. And yet...

Also, regarding Albain...surgeons' blind faith in that post hoc analysis lead to them cutting on way too many people when the clearly better answer is to save the pt of any post-op M&M, and give the powerful agent known as durva thereafter. Can't do all that if you cut because you put all your faith in a post hoc analysis.

 

[FrostyHammer]

Sounds like Frosty is intimidated by Spratt or has some personal beef. Weird, as I met Spratt on a rotation and he is really nice. The residents love him.

Nguyen said Spratt’s study was super strong and that he himself will think hard before giving ADT reflexively.

The whole point of Spratt’s talk was that PSA is a predictive biomarker. Nguyen confirmed all the harms of ADT. Great interview on quadshot.

I went to ASTRO this year and thought it was one of the most important talks and guidelines are going to change I am told to better enforce shared decision making, and given RAVES data.

Spratt showed the credibility criteria even and Nguyen agreed it was a very robust secondary analysis.

Considering the author line is comprised of most of the nations prostate experts I think it was an NRG team effort that Spratt was the 1st author of. Criticism is being made to most of the GU experts like Sandler and Shipley.

I bet if Frosty messaged him on twitter he would happily discuss as he seems to respond to everyone. I messaged him about jobs and he helped out.

Never met the guy, nothing personal but I have heard many stories exactly the opposite about him. Please see the complete discussion above including Scar's excellent eloquence on this topic, which I believe much more than Spratt's biased guns-ablazing logic. If I had Twitter, I would also directly tell him; I'm sure you can help out with that if desired.

 

[westcoastonc]

Funny that you keep saying guns a blazing when all I saw was a great presenter trying to help patients. Not sure why you take the results so personally unless you have some COI with bicalutamide.

Regardless, I did my masters in biostats so I get compelled to respond given the confusion on this thread.

As Spratt said in the quadshot interview, there is no magic cut point. PSA is a continuous variable and it is predictive across the spectrum of the trial. However to show a Kaplan Meier curve you have to pick a cutpoint for 2 groups. The most rigorous cutpoint is obviously the stratification variable used in the trial.

As he said, getug16 has longterm follow up now with no OS benefit. Furthermore, the MFS benefit is suspect given it was posthoc and retrospectively collected. Watch the ASCO discussant. Nguyen even said this that there is no real MFS benefit in getug if you watch it again.

Furthermore 50% of patients had PSA over 0.3. What Spratt asked them to do in the ASTRO talk was show their results by PSA. Same for Rtog 0534, which still hasn’t shown an MFS difference. If those trials prove him wrong great. If they don’t, he obviously was right.

So overall not sure why ppl are so Pro hormones here. No data to suggest survival or Mets benefit for low PSAs.

Regardless, sounds like Frosty should have a 1 on 1 with him and clear the air. Seems odd to flame ppl who you have never met who are spending their careers trying to move the field forward, like all of us. Fine to disagree with the data, but to try to invalidate data based on some insecurity you have is odd.

Happy to post on twitter. Message me your name so he can contact you.

Never met the guy, nothing personal but I have heard many stories exactly the opposite about him. Please see the complete discussion above including Scar's excellent eloquence on this topic, which I believe much more than Spratt's biased guns-ablazing logic. If I had Twitter, I would also directly tell him; I'm sure you can help out with that if desired.

 

[FrostyHammer]

Funny that you keep saying guns a blazing when all I saw was a great presenter trying to help patients. Not sure why you take the results so personally unless you have some COI with bicalutamide.

Regardless, I did my masters in biostats so I get compelled to respond given the confusion on this thread.

As Spratt said in the quadshot interview, there is no magic cut point. PSA is a continuous variable and it is predictive across the spectrum of the trial. However to show a Kaplan Meier curve you have to pick a cutpoint for 2 groups. The most rigorous cutpoint is obviously the stratification variable used in the trial.

As he said, getug16 has longterm follow up now with no OS benefit. Furthermore, the MFS benefit is suspect given it was posthoc and retrospectively collected. Watch the ASCO discussant. Nguyen even said this that there is no real MFS benefit in getug if you watch it again.

Furthermore 50% of patients had PSA over 0.3. What Spratt asked them to do in the ASTRO talk was show their results by PSA. Same for Rtog 0534, which still hasn’t shown an MFS difference. If those trials prove him wrong great. If they don’t, he obviously was right.

So overall not sure why ppl are so Pro hormones here. No data to suggest survival or Mets benefit for low PSAs.

Regardless, sounds like Frosty should have a 1 on 1 with him and clear the air. Seems odd to flame ppl who you have never met who are spending their careers trying to move the field forward, like all of us. Fine to disagree with the data, but to try to invalidate data based on some insecurity you have is odd.

Happy to post on twitter. Message me your name so he can contact you.

Not doubting that he's a good presenter or takes patient care seriously. What I abhor about him is the way he delivers his message. As if his strong views are the only thing that's right in the world. There is one thing to state your opinion, but there is another that imposes your opinion on others. And the latter is wrong.

I'm glad you have a masters in biostats, but surely you must know that because there is no precise cutpoint, the results by definition need to be taken cautiously. If you actually read the discussion above, that's why post-hoc analyses are dangerous... because the person can manipulate any threshold to argue whatever he wants. See the discussion on hypofrac for TNBC. We rightfully chide surgeons for operating on IIIA lung based on Albain study post-hoc analysis, which hasn't been recapitulated by other similar randomized trials. There are examples of this littered all over the literature.

By the way, I'm sure your MS in biostats also taught you that, regarding getug and other randomized trials, the endpoint being nonsignificant with time isn't a big deal. Why? Endpoints are specified and powered for a particular time point. Getug's PEP at the specified time point was reported by the Lancet Oncology pub. If you don't believe me, believe that no one will be changing their practice based on the negative longer term results of eortc 22922 despite the positive findings in the NEJM paper. If you still don't believe me, check out the famous Mack Roach editorial reply to Tony D'Amico on his RTOG trial stating the importance of the primary endpoint being for a particular time point.

 

[evilbooyaa]

Sounds like Frosty is intimidated by Spratt or has some personal beef. Weird, as I met Spratt on a rotation and he is really nice. The residents love him.
I messaged him about jobs and he helped out.

I mean, I don't know either of these two folks (Frosty or Spratt) separately, but sounds like he just disagrees with Spratt's interpretation of the data. You seem to be projecting, somewhat, in that regard.

Maybe you're just white knighting for Spratt since you messaged him and he helped you out? Do you see the path to that conclusion when you go after somebody for their opinion as simply being 'anti-Spratt' as if Dan Spratt ****ed Frosty's girlfriend/boyfriend or peed in his/her cereal, and that's why Frosty doesn't 'like' Spratt?

Again, not knowing Spratt, he presents what are, to some extent, his opinions, as facts, like the applicability of a post-hoc analysis. All the time. He's very vocal about his opinions and does not qualify any statements with "I know there are multiple ways to evaluate this but I believe...." Not saying he's necessarily wrong but one of the most important things about this field is understanding the difference between variation in practice and malpractice.

That's OK for him to do that, and it's OK to disagree with him for having that personality trait without it coming off as "lol you just don't like Spratt".

 

[Palex80]

You know what is really sad besides the fact that this thread has become kind of a "with Spratt" / "against Spratt" debate?

The fact that the single abstract / presentation of this years ASTRO congress that apparently is causing all this discussion and debate (regardless of how it was presented) was a post-hoc subset analysis of a randomized trial run in the 90s...
This speaks volumes on the quality and significance of what is being presented at ASTRO...

 

[scarbrtj]

You know what is really sad besides the fact that this thread has become kind of a "with Spratt" / "against Spratt" debate?

The fact that the single abstract / presentation of this years ASTRO congress that apparently is causing all this discussion and debate (regardless of how it was presented) was a post-hoc subset analysis of a randomized trial run in the 90s...
This speaks volumes on the quality and significance of what is being presented at ASTRO...

 

[medgator]

You know what is really sad besides the fact that this thread has become kind of a "with Spratt" / "against Spratt" debate?

The fact that the single abstract / presentation of this years ASTRO congress that apparently is causing all this discussion and debate (regardless of how it was presented) was a post-hoc subset analysis of a randomized trial run in the 90s...
This speaks volumes on the quality and significance of what is being presented at ASTRO...

I've said for years that anything oncologically significant gets published in the JCO and presented at ASCO...

Hopefully ESTRO does better?

 

[westcoastonc]

So funny that some of you pretend you know how to do any of this better. Or how you criticize presenters who all of you say you don’t even know the guy, but make comments as if you know him and how that has anything to do with the validity of the data. I never got the impression that he thinks his opinion is fact. Sounds like you may have insecurities to create some persona for a random guy you don’t know. I guess I have never assumed the personality traits of experts in our field I don’t know.

Remind me, are any of you GU experts like Spratt, Sandler, Feng, Shipley, Pisansky, etc who did that work? NRG stats with Dignam is an expert but I am sure you know more about stats then him. Easy to repeat words like, posthoc, and ignore the credibility criteria of subset analyses

I agree that it would be great if ASTRO had better trials. I think we all agree on that. I do think you will be surprised at how many will not be using as much ADT if the published paper shows the same thing.

I always need to see the full paper to assess the stats as you never see enough in an abstract or talk. Just the highlight reel.

I agree that if it ends up in PRO it likely has major stats probs. If in Lancet Onc, Jama Onc, or JCO likely more credible.

I mean, I don't know either of these two folks (Frosty or Spratt) separately, but sounds like he just disagrees with Spratt's interpretation of the data. You seem to be projecting, somewhat, in that regard.

Maybe you're just white knighting for Spratt since you messaged him and he helped you out? Do you see the path to that conclusion when you go after somebody for their opinion as simply being 'anti-Spratt' as if Dan Spratt ****ed Frosty's girlfriend/boyfriend or peed in his/her cereal, and that's why Frosty doesn't 'like' Spratt?

Again, not knowing Spratt, he presents what are, to some extent, his opinions, as facts, like the applicability of a post-hoc analysis. All the time. He's very vocal about his opinions and does not qualify any statements with "I know there are multiple ways to evaluate this but I believe...." Not saying he's necessarily wrong but one of the most important things about this field is understanding the difference between variation in practice and malpractice.

That's OK for him to do that, and it's OK to disagree with him for having that personality trait without it coming off as "lol you just don't like Spratt".

 

[scarbrtj]

So funny that some of you pretend you know how to do any of this better. Or how you criticize presenters who all of you say you don’t even know the guy, but make comments as if you know him and how that has anything to do with the validity of the data. I never got the impression that he thinks his opinion is fact. Sounds like you may have insecurities to create some persona for a random guy you don’t know. I guess I have never assumed the personality traits of experts in our field I don’t know.

Remind me, are any of you GU experts like Spratt, Sandler, Feng, Shipley, Pisansky, etc who did that work? NRG stats with Dignam is an expert but I am sure you know more about stats then him. Easy to repeat words like, posthoc, and ignore the credibility criteria of subset analyses

I agree that it would be great if ASTRO had better trials. I think we all agree on that. I do think you will be surprised at how many will not be using as much ADT if the published paper shows the same thing.

I always need to see the full paper to assess the stats as you never see enough in an abstract or talk. Just the highlight reel.

I agree that if it ends up in PRO it likely has major stats probs. If in Lancet Onc, Jama Onc, or JCO likely more credible.

Can definitely trust an article (and by extension, change or not change your clinical practice) based on in which journal it's published. I kid, I kid!