ASTRO Congress News

[Chartreuse Wombat]

Awaiting full paper. Potentially enough of an effect to change OM but I doubt they have the power. Paul Nguyen did a great job comparing GETUG to 9601. The ASCO update had median FU just shy of 10 years (112 months). 9601 publication median FU was 13 years. All about the number of informative events. The baseline rate of PCSM must be higher with 9601 (stage/grade migration and higher preRT PSA) and I bet the effect of ADT will be smaller as well.

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[Krukenberg]

I share the same bias.

Two additional RCTs are relevant to the question: RTOG 0534 (plenary at ASTRO 2018) and GETUG (update presented at ASCO 2019).

Both of these studies were more contemporary than 9601 and the range of preRT PSA was much lower. GETUG median 0.3 IQR 0.2-0.5 RTOG 0534 median 0.34 with 95% below 1.0

I won't change my practice until a hard endpoint like DM, PCSM or OM are changed.

0534 is too premature
GETUG update reported improvement in distant metastases at 10 years. (verbatim below from abstract)
"Metastatic free survival (MFS) is significantly improved in the combined arm (HR = 0.73 [CI95% = 0.54-0.98] ; p =
0.034) with 69% [CI95% = 63-74] versus 75% [CI95% = 70-80] of MFS at 10 years for RT alone and RT+HT, respectively."

So there are hints that STADT will move the needle on a hard endpoint with lower PSAs but we need to wait for more events.

Did Nguyen bring up the GETUG update showing DMFS benefit to ADT? Seems very pertinent given the assertions spratt is making about low pre-rt psa.

 

[Chartreuse Wombat]

Yes and provided a nice slide comparing the timeline of 9601 presented at ASTRO 2010 with DM improvement resulting in OM improvement in 2017.

Dan was the discussant at ASCO 2019 when the GETUG update was presented. Basically he said "meh" no survival advantage no need to change practice. That is a defensible position but it is a high bar. Lots of what we do doesn't have OM evidence

 

[evilbooyaa]

Yes and provided a nice slide comparing the timeline of 9601 presented at ASTRO 2010 with DM improvement resulting in OM improvement in 2017.

Dan was the discussant at ASCO 2019 when the GETUG update was presented. Basically he said "meh" no survival advantage no need to change practice. That is a defensible position but it is a high bar. Lots of what we do doesn't have OM evidence

The extreme of 'ADT in low PSA should be avoided in all costs' bias, IMO.

Metastatic prostate cancer sucks. DMFS is a more than sufficient end-point for me to change practice. That abstract, and the full paper that will follow it, will likely change my practice to offer 6 months of ADT to all, regardless of PSA.

 

[FrostyHammer]

Yes and provided a nice slide comparing the timeline of 9601 presented at ASTRO 2010 with DM improvement resulting in OM improvement in 2017.

Dan was the discussant at ASCO 2019 when the GETUG update was presented. Basically he said "meh" no survival advantage no need to change practice. That is a defensible position but it is a high bar. Lots of what we do doesn't have OM evidence

Again, I won't trust Spratt and his guns-ablazing opinions. How many things can you think of in prostate cancer that don't have a survival advantage that we do routinely? Ever heard of bPFS? I agree with evilbooyaa's point above about DMFS.

 

[Krukenberg]

Again, I won't trust Spratt and his guns-ablazing opinions. How many things can you think of in prostate cancer that don't have a survival advantage that we do routinely? Ever heard of bPFS? I agree with evilbooyaa's point above about DMFS.

To be fair Spratt bashes bPFS all the time as an endpoint. It’s the whole basis of his critique of combined ebrt +brachy.

 

[Palex80]

Whether or not DMFS is a valid endpoint is a good question. A debate has been going on amond medical oncologists as well, after the three randomized trials testing new agents for non-metastatic castration resistant prostate cancer looked into DMFS as an endpoint.
The other "problem" with DMFS is that it is "evolving" over time due to better imaging. It's not a "hard" endpoint like OS (you are either dead or not), it's a more "fluid" endpoint which has to do a lot with a) how often you perform imaging and b) what kind of imaging you are performing.
Is a 5mm bone lesion picked up by PSMA-PET-CT a surrogate marker for OS? Noone knows...

 

[evilbooyaa]

Again, I won't trust Spratt and his guns-ablazing opinions. How many things can you think of in prostate cancer that don't have a survival advantage that we do routinely? Ever heard of bPFS? I agree with evilbooyaa's point above about DMFS.

Spratt has a slide in his brachy boost talk presented at ASTRO 2019, which focuses on poo-pooing the concept of brachy boost in its entirety, saying DMFS, but not local recurrence (like clinical recurrence) is a surrogate for OS.

For him to say from the GETUG data that DMFS is no longer sufficient and only OS matters is hypocritical.

Spratt has a tendency to speak out of both sides of his mouth depending on the scenario. He flip flops worse than John Kerry did.

BTW, IIRC, it was posted when he was having a spat with Zelefsky (his prostate mentor at MSKCC when he was a resident) that his NRG-GU006 primary end-point is..... bPFS. The same bPFS he rails against the brachy community for supporting, the same bPFS he doesn't believe in with ADT in low-PSA salvage patients.

He has strong opinions but is not consistent with his opinions which is why it's difficult for me to take him serious sometimes.

 

[FrostyHammer]

To be fair Spratt bashes bPFS all the time as an endpoint. It’s the whole basis of his critique of combined ebrt +brachy.

He bashes it when convenient, and follows it when also convenient. Welcome to the future of rad onc, med students...

 

[Gfunk6]

ESMO 2019: Largest ever trial in postoperative prostate cancer patients confirms that men can be spared radiotherapy after surgery

Men with prostate cancer can be spared radiotherapy after surgery, according to late breaking results from a study presented at the ESMO Congress in Barcelona.

www.icr.ac.uk

what do you guys make of this?

practice changing or already consistent with what you're doing ?

It looks like inclusion criteria for post-op XRT included pre-op PSA > 10 and GS 7 (on surgery or biopsy). Neither is an indication for PORT in US - so may have contaminated results.

 

[evilbooyaa]

ESMO 2019: Largest ever trial in postoperative prostate cancer patients confirms that men can be spared radiotherapy after surgery

Men with prostate cancer can be spared radiotherapy after surgery, according to late breaking results from a study presented at the ESMO Congress in Barcelona.

www.icr.ac.uk

what do you guys make of this?

practice changing or already consistent with what you're doing ?

Correlates well with the RAVES data despite the differences noted by GFunk above.

I mean I wasn't routinely getting consults for adjuvant radiation anyways, but honestly I'd be happy to get involved in post-op surveillance in patients that would've met high-risk criteria if the Urologists want me to. 50% treatment rate in the obs arm in RAVES isn't bad. Not sure what it is in RADICALS as I didn't go to ESMO.

 

[BobbyHeenan]

I’m more convinced now to avoid adjuvant (except in the worst of the worst like a G9 with a +margin)....

The challenge in my neck of the woods is getting urology to refer when that first + PSA occurs....I get patients 2-3 years later with a PSA of now like 0.8 and I’m like where TF was this referral 2 years ago? Why did we just decide to recheck PSAs for 2 years?

 

[Mandelin Rain]

I've been routinely offering early salvage for all but the worst cases (as above, margin always being the tie breaker) for years.

It's a pain seeing a guy you haven't (may not) treat every three months and discussing primarily his surgery induced incontinence and impotence, but I figured it was the right thing to do.

Upside is I can spare a healthy percentage of guys XRT. Downside is I give most of the ones I do treat short-term ADT.

 

[xrthopeful]

I've been routinely offering early salvage for all but the worst cases (as above, margin always being the tie breaker) for years.

It's a pain seeing a guy you haven't (may not) treat every three months and discussing primarily his surgery induced incontinence and impotence, but I figured it was the right thing to do.

Upside is I can spare a healthy percentage of guys XRT. Downside is I give most of the ones I do treat short-term ADT.

if you're following them fairly closely, I feel like you can still avoid ADT. The 0.08s etc.

 

[FrostyHammer]

if you're following them fairly closely, I feel like you can still avoid ADT. The 0.08s etc.

Here we go with the Spratt logic again...

 

[xrthopeful]

Spratt logic?

Wait are you routinely giving ADT for -ANYONE- who you are giving salvage to?

Um.

 

[FrostyHammer]

Spratt logic?

Wait are you routinely giving ADT for -ANYONE- who you are giving salvage to?

Um.

With PSA of 0.2+, yes.
PSA detectable but <0.2 is historically not called salvage.

 

[medgator]

With PSA of 0.2+, yes.
PSA detectable but <0.2 is historically not called salvage.

I consider it salvage if a psa is or isn't detectable post op and the surgeon waited for it to rise before sending it to me. I've also heard a definition defined by at least 6 months postop being the cut off. Imo any detectable psa fits the salvage definition. PSA should be undetectable after RP

 

[xrthopeful]

With PSA of 0.2+, yes.
PSA detectable but <0.2 is historically not called salvage.

I don’t care about history. This is 2019. You should be advocating with your referring to see these early salvage cases when PSA is rising, ideally well before 0.2.

 

[FrostyHammer]

I don’t care about history. This is 2019. You should be advocating with your referring to see these early salvage cases when PSA is rising, ideally well before 0.2.

Hahaha. Good luck advocating that to any urologist in the real world. Great thought in principle though.

 

[FrostyHammer]

I consider it salvage if a psa is or isn't detectable post op and the surgeon waited for it to rise before sending it to me. I've also heard a definition defined by at least 6 months postop being the cut off. Imo any detectable psa fits the salvage definition. PSA should be undetectable after RP

That's fine. Remember though that RAVES labels "early salvage" as 0.2. Just going by the data regardless of semantics. Radicals uses 0.1 so perhaps when that's published this issue can be revisited.

 

[xrthopeful]

Hahaha. Good luck advocating that to any urologist in the real world. Great thought in principle though.

I mean that's where all the data is.

This paper in the JCO shows that outcomes with salvage are worse past 0.2 compared to less than 0.2 Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy. - PubMed - NCBI

also, RTOG 0534 itself used 0.1 as an entry point criteria for enrollment. In 2005.

0.2 is old old old old old news.

 

[xrthopeful]

anyways I am sure practice patterns are different in different places and you are not yet getting referrals before 0.2, I hope you are.

But my initial post you replied to was directed to Mandelin Rain - who IS getting undetectable referrals and then is appropriately treating them only when PSA is rising. My point to him was that he didn't necessarily have to give them all ADT. Since he's seeing them, and following their PSAs, he's likely catching tons of people with 0.06s and 0.11s who don't need ADT really.

 

[FrostyHammer]

I mean that's where all the data is.

This paper in the JCO shows that outcomes with salvage are worse past 0.2 compared to less than 0.2 Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy. - PubMed - NCBI

also, RTOG 0534 itself used 0.1 as an entry point criteria for enrollment. In 2005.

0.2 is old old old old old news.

That's fine, I see your point, just saying that many people are waiting for trials to get published rather than rely on retrospective data like what you cited above. 0534 hasn't been completely published and so what I said above about the publication of radicals also applies. I hope that this discussion happens meaningfully in the field once they get published. In the meantime, urology society recommendations and guidelines all still state to refer for 0.2+.

 

[medgator]

I don’t care about history. This is 2019. You should be advocating with your referring to see these early salvage cases when PSA is rising, ideally well before 0.2.

I've had urologists in 2018-2019 watch a node+ pt post RP and wait to send it to me until the PSA started rising

 

[evilbooyaa]

Here we go with the Spratt logic again...

C'mon man. It's not 'Spratt' logic to blanket not give ADT to everybody getting salvage. Neither RAVES nor RADICALS used ADT for their early salvage patients.

 

[BobbyHeenan]

I mean that's where all the data is.

This paper in the JCO shows that outcomes with salvage are worse past 0.2 compared to less than 0.2 Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy. - PubMed - NCBI

also, RTOG 0534 itself used 0.1 as an entry point criteria for enrollment. In 2005.

0.2 is old old old old old news.

I agree, but even "well read" urologists at Mayo wait to send according to twitter hearsay below. I'm going to talk to my urologists about OK to not send every adjuvant case, but PLEASE send me first + PSA they pop and don't sit on it. We'll see...

 

[medgator]

C'mon man. It's not 'Spratt' logic to blanket not give ADT to everybody getting salvage. Neither RAVES nor RADICALS used ADT for their early salvage patients.

I do plenty of salvage without it. Why would I give someone with low volume 3+4=7 disease with a slow PSA-DT and a +margin ADT?

Wouldn't do it for intact disease with xrt, so he doesn't need it now

 

[RadOncDoc21]

Damn, I haven’t had a prostate cancer patient in over 2 yrs. The urology group here has their own urorad and there are no other urologists in the area. I am enjoying the discussion and picturing what I would do.

Sorry, carry on...

 

[xrthopeful]

I do plenty of salvage without it. Why would I give someone with low volume 3+4=7 disease with a slow PSA-DT and a +margin ADT?

Wouldn't do it for intact disease with xrt, so he doesn't need it now

Here we go with the Spratt logic again.....

 

[medgator]

Here we go with the Spratt logic again.....

Seems like plain old logic to me. Why does that pt need ADT at all?

 

[xrthopeful]

Seems like plain old logic to me. Why does that pt need ADT at all?

I guess the joke didn't land. Scroll back up and see what Frosty said.

 

[medgator]

I guess the joke didn't land. Scroll back up and see what Frosty said.

I still don't get it. Whatever

 

[xrthopeful]

I still don't get it. Whatever

basically FrostyHammer would see your post and call it Spratt Logic.

 

[medgator]

basically FrostyHammer would see your post and call it Spratt Logic.

I still don't understand how that's funny or related to spratt, granted I don't know spratt at all, he's probably younger than I am lol

 

[xrthopeful]

I still don't understand how that's funny or related to spratt, granted I don't know spratt at all, he's probably younger than I am lol

It's not funny really.

I said what you said that not all salvage patients need ADT, and Frosty called that 'Spratt' logic. see above

You said (which I agree with) that not all salvage patients need ADT, so I just replied with what Frosty said.

anyways the Spratt thing came from an ASTRO plenary where he did a post-hoc analysis of 9601 showing that patients with PSA below 0.7 may actually be more harmed than helped by ADT in salvage setting.

people have issue with the stats of what he did.

My point is really independent of the Spratt analysis - it's fairly common sense stuff to think that someone getting salvaged with a PSA of 0.08 and a positive margin doesn't need ADT.

 

[deleted1002574]

It’s really hard to stomach that this guy gets a “logic” named after him, even if that means “shoddy logic”.

 

[xrthopeful]

 

[Chartreuse Wombat]

Technically RADICALS-RT did not meet the prespecified NI criterion, but if the data support your bias to hell with the hypothesis.

I prefer not to treat men that don't need it and have recommended early salvage for years. Nationwide the utilization of adjuvant RT is very low regardless of what the guidelines recommend.

Will be interesting to see what happens with patterns of care with the change in ADT recommendations in the latest update.

 

[evilbooyaa]

Technically RADICALS-RT did not meet the prespecified NI criterion, but if the data support your bias to hell with the hypothesis.

Correct in all aspects. I'm cognizant of my bias and taken with the results of RAVES makes me strongly consider SRT rather than ART in this patient population.

 

[scarbrtj]

I saw this. I haven't really thought much about it yet. Someone may wanna wax eloquent about how RADICALS addressed different questions than ARO 9602 did which seemed, to me, to show adjuvant RT (aka aRT) was significantly better than salvage (aka eSRT). But maybe I'm mis-seeing the studies' aims/outcomes. If I'm not, then no @RealProstateDoc, I wouldn't say it's *the* standard of care (aka SOC). Maybe *a* SOC. Whereas before I thought there was *one* SOC, aRT, there's now two SOCs, aRT & eSRT.

it's fairly common sense stuff to think that someone getting salvaged with a PSA of 0.08 and a positive margin doesn't need ADT.

"Common sense?" Risk vs benefit re: duration of the hormone therapy, many many arrows pointing toward anti-androgen (aka AAT) benefit as a class solution (perhaps AAT is a radiation sensitizer and provides radiation synergistic effects). There's no reason AAT+RT would be less oncologically effective than RT alone and optimizing its duration may be key... a Goldilocks approach if you will where detriment doesn't outweigh benefit, even in the PSA<0.1 aRT setting. Maybe RTOG 9601's 2y of AAT is the-porridge-is-too-hot amount of AAT (for all-comers).

"Don't let the idea of immediate adjuvant treatment go away too soon, keep America great!" - Donald Trump*, M.D.
*real guy

 

[xrthopeful]

I don’t see the argument at all for adjuvant with this preponderance of data.

If you’re getting the adjuvant consults, that’s good, you can catch them at early salvage and avoid unnecessary RT for others

 

[FrostyHammer]

C'mon man. It's not 'Spratt' logic to blanket not give ADT to everybody getting salvage. Neither RAVES nor RADICALS used ADT for their early salvage patients.

BTW, not sure if people understood, but my definition of "Spratt logic" as contextualized above means creating a random a priori threshold and using it as absolute justification to do a particular course of action, especially when not putting it in context of other salient factors. The post above was referring to an arbitrary PSA value of 0.08 whether to give it not, hence my reply as such.

 

[thesauce]

Just want to throw out something interesting: I had a patient sent to me pre-surgery with low intermediate risk disease (3+4 in low volume, PSA 6, cT1c). decided to go for surgery and was found to have pT2N0 disease with negative margins, etc.

4 weeks post-op, his PSA was 1.0. Repeat a month later was 2.0. BS and CT was negative. I recommended salvage RT. Patient went to an academic center and they said it was metastatic and start on ADT and Xtandi. Said savage RT would not be helpful because margins were negative.

So I looked it up and there are 5 studies that look at the benefit of salvage RT. Only 2 of the 5 found margin status to be a significant predictor of the benefit of salvage RT. One factor that was consistently seen as a predictor for the benefit of salvage was PSA doubling time and clearly his was short.

I just found this interesting. I heard from I don’t know how many people that margin status was all that mattered, but turns out it isn’t as important as one of the clear factors that he had which wasn't mentioned once...

 

[BobbyHeenan]

Just want to throw out something interesting: I had a patient sent to me pre-surgery with low intermediate risk disease (3+4 in low volume, PSA 6, cT1c). decided to go for surgery and was found to have pT2N0 disease with negative margins, etc.

4 weeks post-op, his PSA was 1.0. Repeat a month later was 2.0. BS and CT was negative. I recommended salvage RT. Patient went to an academic center and they said it was metastatic and start on ADT and Xtandi. Said savage RT would not be helpful because margins were negative.

So I looked it up and there are 5 studies that look at the benefit of salvage RT. Only 2 of the 5 found margin status to be a significant predictor of the benefit of salvage RT. One factor that was consistently seen as a predictor for the benefit of salvage was PSA doubling time and clearly his was short.

I just found this interesting. I heard from I don’t know how many people that margin status was all that mattered, but turns out it isn’t as important as one of the clear factors that he had which wasn't mentioned once...

Did they at least check an Axumin PET?

 

[scarbrtj]

Just want to throw out something interesting: I had a patient sent to me pre-surgery with low intermediate risk disease (3+4 in low volume, PSA 6, cT1c). decided to go for surgery and was found to have pT2N0 disease with negative margins, etc.

4 weeks post-op, his PSA was 1.0. Repeat a month later was 2.0. BS and CT was negative. I recommended salvage RT. Patient went to an academic center and they said it was metastatic and start on ADT and Xtandi. Said savage RT would not be helpful because margins were negative.

So I looked it up and there are 5 studies that look at the benefit of salvage RT. Only 2 of the 5 found margin status to be a significant predictor of the benefit of salvage RT. One factor that was consistently seen as a predictor for the benefit of salvage was PSA doubling time and clearly his was short.

I just found this interesting. I heard from I don’t know how many people that margin status was all that mattered, but turns out it isn’t as important as one of the clear factors that he had which wasn't mentioned once...

This is the one situation I find closest to being a Pascal's wager. There's (likely) no way to prove to any level of satisfaction right now the man has either local disease or metastatic disease. Assuming RT at this point would leave him with few if any side effects, and also would not preclude also proceeding onward with AAT+xtandi, subsitute "God exists" with "localized disease" and "no God" with "metastatic disease" and the "What to do with your life" with "pursue local RT."

 

[thesauce]

Did they at least check an Axumin PET?

Yes and it was negative

 

[thesauce]

This is the one situation I find closest to being a Pascal's wager. There's (likely) no way to prove to any level of satisfaction right now the man has either local disease or metastatic disease. Assuming RT at this point would leave him with few if any side effects, and also would not preclude also proceeding onward with AAT+xtandi, subsitute "God exists" with "localized disease" and "no God" with "metastatic disease" and the "What to do with your life" with "pursue local RT."

This is what he wants to do, but the academic center med onc said post-op RT would be “highly toxic” and said no benefit with negative margins

 

[scarbrtj]

This is what he wants to do, but the academic center med onc said post-op RT would be “highly toxic” and said no benefit with negative margins

So I hope he (the patient) does what he wants to do. And he saw a med onc? Seeing a med onc when you have, or could have, localized prostate cancer is in and of itself a risk for iatrogenicity.

 

[Mandelin Rain]

I hate that I'm now going to incorporate Pascal's Wager into consultative visits.

Best sentence to combat what academic med onc said... "Do you want to be aggressive with your cancer treatment?" People usually respond immediately to that question.

I would tell the guy flatly, it's likely that he has disease elsewhere and the chance of successful salvage is low, but it's not 0%. If he wants to be AGGRESSIVE, it is his only potential pathway to cure, with the understanding that there is also a non-0% chance of side effects.