Race to the bottom

[Ray D. Ayshun]

"I didn't want prostate cancer to slow me down. I wanted prostate cancer treatment to do it."

Are people SBRTing the SVs, or 5x5?

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Members don't see this ad.

 

[radonc17]

Here's one of the first pages in my most recent New Yorker

NYC marketing game is unreal. Been an issue for years! Illuminating NYT article from 2009

Cancer Center Ads Use Emotion More Than Fact (Published 2009)

Advertisements for cancer centers can get away with statements that would be off-limits to drug makers.

www.nytimes.com

This ad is from Winthrop hospital, aka Cyberknife U, following merger with NYU

winthrop been doing shady ads for years

Cornell, MSKCC, LIJ, Sinai not much better unfortunately

 

[Radonky]

POP-RT benefitted from PSMA. Patients likely truly had microscopic disease that would benefit from ENI. Distant disease would have been weeded out. Without PSMA, it likely would be a negative trial.

 

[FrostyHammer]

I don't understand the hesitation people are having with SBRT for high risk disease. No we dont have long followup data but we have medium followup data that it is safe and effective. Do people really think the failures in high risk disease are because the PTV margin was tight as opposed to out of field recurrences?

Aren't people using similar margins with modern IMRT anyway?

My main beef is what to do with nodes. Not enough good quality data on 5x5 or other approaches. I have no problems with those "lower" high risk cases where nodal risk is lower, but would I really want to omit nodes for a 5+4 cT3b cancer?

 

[medgator]

My main beef is what to do with nodes. Not enough good quality data on 5x5 or other approaches. I have no problems with those "lower" high risk cases where nodal risk is lower, but would I really want to omit nodes for a 5+4 cT3b cancer?

Even a urologist is going to sample them (many of them are skipping lymphadenectomy now in low/int risk cases)

 

[thecarbonionangle]

Even a urologist is going to sample them (many of them are skipping lymphadenectomy now in low/int risk cases)

Urologists come in all shapes and forms, like a beautiful tamarind. Some do a “lympadenectomy” and take out 3 nodes. Some take out 40-60, you just never know!!!

 

[ramsesthenice]

My main beef is what to do with nodes. Not enough good quality data on 5x5 or other approaches. I have no problems with those "lower" high risk cases where nodal risk is lower, but would I really want to omit nodes for a 5+4 cT3b cancer?

now you are talking about the guys even I treat nodes in. These dudes also tend to have pretty high volume disease too. My preference is to go for combo EBRT HDR for these folks. The data for an SBRT boost is getting a little interesting too.

 

[drewdog1973]

Urologists come in all shapes and forms, like a beautiful tamarind. Some do a “lympadenectomy” and take out 3 nodes. Some take out 40-60, you just never know!!!

The imagery is fantastic. Well played!

 

[RadOncG]

That's been the case for decades This guy had some great radio ads back in the day ...

Gil Lederman's Dubious Career - Nymag

When the notorious cancer doctor Gil Lederman cadged an autograph from a dying George Harrison, the world was appalled.But as Lederman scrambles to salvage his reputation, the very nature of his experimental practice has come under attack.

nymag.com

Now all academic centers are Gil Lederman at a much higher price. Academic centers are visionaries with their PROMISE service lines. Gil Lederman a quack.

Both well ahead of the data. Hopefully it turns out to be evidence based eventually. Our careers depend on it.

 

[FrostyHammer]

now you are talking about the guys even I treat nodes in. These dudes also tend to have pretty high volume disease too. My preference is to go for combo EBRT HDR for these folks. The data for an SBRT boost is getting a little interesting too.

What do you make of the ASCENDE RT data then, which was barely significant but with inadequate ADT duration in the high risk patients, so unclear overall?

 

[ramsesthenice]

What do you make of the ASCENDE RT data then, which was barely significant but with inadequate ADT duration in the high risk patients, so unclear overall?

Not sure yet. My main interest is local control. Local failures can be disastrous and with better systemic options it will probably continue to become more important. I struggle to rationalize why a higher BED in the primary would give better distant control. I mean, people argue that primary failures lead to distant failures so there should be a correlation. It’s not immediately clear to me how valid that argument is as local only failures after RT are the exception and not the rule. At this point I am not convinced HDR (or SBRT) boosts will give better systemic control. But I do think you get better in gland control with no to minimal increased toxicity with HDR (as opposed to LDR).

 

[thesauce]

The general concern is with the tight margins and limited SV coverage we use with SBRT. Hypothetically high risk patients have a higher risk of microscopic extension which might not be adequately covered. It has nothing to do with biologic responses to treatment. Its all technical. I bet it eventually turns out to be bull**** too. That said, the only high risk folks I use SBRT on are those with low volume disease.


The people that trained me trained at Harvard and were pretty against nodal coverage as well. I rarely treat nodes myself (though I do it more than they do).

How much of the SVs do you cover with SBRT?

 

[ramsesthenice]

How much of the SVs do you cover with SBRT?

No more than 1 cm

 

[RickyScott]

No more than 1 cm

Extent of almost all sv invasion is within .3cm of prostate. Sbrt may very well be legit for high risk prostate, but it will mean that almost all prostate can be treated in 5 fractions and that many pts can travel to large centers for treatment, centralizing treatment to some extent. Sheer hypocrisy to push prostate sbrt and residency expansion.

 

[ramsesthenice]

Extent of almost all sv invasion is within .3cm of prostate. Sbrt may very well be legit for high risk prostate, but it will mean that almost all prostate can be treated in 5 fractions and that many pts can travel to large centers for treatment, centralizing treatment to some extent. Sheer hypocrisy to push prostate sbrt and residency expansion.

Wait wait wait. Are you implying you don’t think the big centers will disclose that SBRT isn’t going to be any more effective, that it could actually be done at many community centers, and that on the whole traveling far away for 5 treatments might actually take more time than a hypofrac course locally?

I’ve gotta be honest, I have seen a lot less patient interest in SBRT than I would have expected. For low and favorable IR folks I thought it was going to kill my HDR volume but that has not really happened. Some patient specifically come looking for SBRT, MR, CK, protons, etc but the patients who are truly indifferent walking in the door have not been clamoring for SBRT. I’m sure it has to do with the sell. I guess if I tried saying thing like “why would you do 20-30 treatments when I could do 5” maybe I could drum up more business.

 

[RickyScott]

Wait wait wait. Are you implying you don’t think the big centers will disclose that SBRT isn’t going to be any more effective, that it could actually be done at many community centers, and that on the whole traveling far away for 5 treatments might actually take more time than a hypofrac course locally?

I’ve gotta be honest, I have seen a lot less patient interest in SBRT than I would have expected. For low and favorable IR folks I thought it was going to kill my HDR volume but that has not really happened. Some patient specifically come looking for SBRT, MR, CK, protons, etc but the patients who are truly indifferent walking in the door have not been clamoring for SBRT. I’m sure it has to do with the sell. I guess if I tried saying thing like “why would you do 20-30 treatments when I could do 5” maybe I could drum up more business.

Closing the sale at big centers involves subtlety implying that local center is not sophisticated enough to deliver 5 fractions (and do you really want to be treated by someone who is not on the cutting edge) or that local center is greedy and incentivized to fractionate for $.

 

[RadOncG]

For low and favorable IR folks I thought it was going to kill my HDR volume but that has not really happened.

HDR when active surveillance preferred treatment? Overkill?

 

[TheWallnerus]

The answer to why rad oncs use SBRT to treat prostate is the punchline to that old George Carlin joke “Why does a dog lick his...”

 

[ramsesthenice]

HDR when active surveillance preferred treatment? Overkill?

Everyone gets AS as an option (and preference if life expectancy considerations) and most people pick it. We are only talking about people who refuse AS.

 

[drewdog1973]

Everyone gets AS as an option (and preference if life expectancy considerations) and most people pick it. We are only talking about people who refuse AS.

We literally get almost zero low risk patients referred

 

[ramsesthenice]

We literally get almost zero low risk patients referred

We don’t get many. Almost all of the older patients opt for AS with urology and that is that. We mostly get younger patients who refuse surgery or people who want treatment and know someone who either had a good experience with RT or a bad experience with surgery. Typically they had a dad or uncle who got “seed treatment” and had no trouble. Or they had surgery and piss a little every time they swing too hard with the driver ☹️

Not urology bashing here. My best friend is a urologist and they get the opposite patients too.

 

[RadOncG]

Everyone gets AS as an option (and preference if life expectancy considerations) and most people pick it. We are only talking about people who refuse AS.

Sorry my question was more how do you treat these low riskers. HDR alone or EBRT + HDR boost

 

[ramsesthenice]

Sorry my question was more how do you treat these low riskers. HDR alone or EBRT + HDR boost

Ohhhh. Mono therapy only. No boost for these guys. I only boost patients with high volume UFIR or HR disease.

What I meant was I would have thought SBRT as an alternative would make more people reconsider undergoing an invasive (albeit outpatient) procedure but it really hasn’t.

 

[RadOncG]

Ohhhh. Mono therapy only. No boost for these guys. I only boost patients with high volume UFIR or HR disease.

What I meant was I would have thought SBRT as an alternative would make more people reconsider undergoing an invasive (albeit outpatient) procedure but it really hasn’t.

Thanks. Makes sense.

I was going to say I'm surprised you're volume wasn't down as well if the treatment was EBRT+Brachy for low riskers.

 

[ramsesthenice]

Thanks. Makes sense.

I was going to say I'm surprised you're volume wasn't down as well if the treatment was EBRT+Brachy for low riskers.

Sadly, if I were the unscrupulous type, I could probably get away with it. I have little to no competition in the immediate vicinity and have the advantage of being at the state institution. Fortunately I am not an @ss. Well, at least not that kind of @ss 🙃

 

[evilbooyaa]

Lots of strong opinions in this thread, stated as fact.

1) I think most would do ENI for VHR patients. Where the threshold to do ENI on HR patients is variable. Some are comfortable doing 5Gy x 5 with SBRT to the nodes. I am not and would not personally offer 5Gy x 5 to somebody, but I don't think it's overtly unreasonable.
2) The OP's case, as described, as long as patient is recommended for long-term hormones, is not completely unreasonable.
3) No data to suggest spaceOAR shouldn't be done in Gleason 9 patients.
4) People talking about POP-RT don't realize the significance of 80% of those patients getting a PSMA-PET in interpreting the results. Yes it looks 'too good to be true' but Rad Oncs love poo pooing even good things, so alas, here we are.

 

[ramsesthenice]

4) People talking about POP-RT don't realize the significance of 80% of those patients getting a PSMA-PET in interpreting the results. Yes it looks 'too good to be true' but Rad Oncs love poo pooing even good things, so alas, here we are.

There is a bit of a logic flaw here with the weight given to the use of PSMA PETs in this study. You are arguing the key is their improved sensitivity to rule out patients with occult distant Mets who are unlikely to benefit from regional therapy. I can get behind you so far. Here is where it gets tricky. If regional nodal RT affords you a profound improvement over Prostate only RT in men who are N0 after PET staging, we have to conclude PETs are not good at detecting occult regional disease. If they were, regional RT wouldn’t be able to add much. So are we to conclude PSMAs are simultaneously great at detecting occult distant disease but crappy at detecting occult regional disease?

Look, a little cynicism is a good thing. Are there enough differences between this study and all of it’s predecessors to account for the differences in outcomes? Maybe. I just don’t personally find them compelling enough to say the issue is resolved and ignore mountains of earlier data. Like you said above, for most of us there is a continuum of when to include nodes. I suppose there are some people that always or never include nodes for high risk patients, but I have to assume more people are somewhere in the middle.

 

[Radonky]

There is a bit of a logic flaw here with the weight given to the use of PSMA PETs in this study. You are arguing the key is their improved sensitivity to rule out patients with occult distant Mets who are unlikely to benefit from regional therapy. I can get behind you so far. Here is where it gets tricky. If regional nodal RT affords you a profound improvement over Prostate only RT in men who are N0 after PET staging, we have to conclude PETs are not good at detecting occult regional disease. If they were, regional RT wouldn’t be able to add much. So are we to conclude PSMAs are simultaneously great at detecting occult distant disease but crappy at detecting occult regional disease?

Look, a little cynicism is a good thing. Are there enough differences between this study and all of it’s predecessors to account for the differences in outcomes? Maybe. I just don’t personally find them compelling enough to say the issue is resolved and ignore mountains of earlier data. Like you said above, for most of us there is a continuum of when to include nodes. I suppose there are some people that always or never include nodes for high risk patients, but I have to assume more people are somewhere in the middle.

PSMA is able to detect regional and metastatic disease far better than bone scan and CT, so it would weed out patients with regional and distant disease (who otherwise would have been enrolled and failed without PSMA). The patients enrolled likely had microscopic disease and benefited from ENI. Some extra bonus points for treating to L4/L5 instead of L5/S1, but the money is in the PSMA.

 

[radtothebone]

There is a bit of a logic flaw here with the weight given to the use of PSMA PETs in this study. You are arguing the key is their improved sensitivity to rule out patients with occult distant Mets who are unlikely to benefit from regional therapy. I can get behind you so far. Here is where it gets tricky. If regional nodal RT affords you a profound improvement over Prostate only RT in men who are N0 after PET staging, we have to conclude PETs are not good at detecting occult regional disease. If they were, regional RT wouldn’t be able to add much. So are we to conclude PSMAs are simultaneously great at detecting occult distant disease but crappy at detecting occult regional disease?

Look, a little cynicism is a good thing. Are there enough differences between this study and all of it’s predecessors to account for the differences in outcomes? Maybe. I just don’t personally find them compelling enough to say the issue is resolved and ignore mountains of earlier data. Like you said above, for most of us there is a continuum of when to include nodes. I suppose there are some people that always or never include nodes for high risk patients, but I have to assume more people are somewhere in the middle.

PSMA PET is a great leap, but it’s not a panacea. Sensitivity of around 40% for staging in this recent study from Hopkins. But to your point that may be why pelvic RT helps here.

A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY) - PubMed

The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that ¹⁸F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of...

pubmed.ncbi.nlm.nih.gov

 

[communitydoc13]

4) People talking about POP-RT don't realize the significance of 80% of those patients getting a PSMA-PET in interpreting the results. Yes it looks 'too good to be true' but Rad Oncs love poo pooing even good things, so alas, here we are.

I think I need a lesson on the significance of PSMA-PET.

My understanding was that PSMA-PET reveals PSMA-PET threshold metastatic disease ~30% of the time in high risk patients, changing treatment strategies in these patients (I know this is a gross generalization.) The argument here seems to be that by excluding these patients (well most patients got PSMA in POP-RT) only regionally advanced patients were included and that these patients derived maximum benefit from regional RT.

However, what would happen if you didn't exclude these patients? Well, here is what happened in Stampede Trial low metastatic burden patients with evident metastatic disease on standard imaging and treatment to the prostate only. These curves are driven by biochemical failures.

Here, it is clearly demonstrated that the presence of higher than PSMA threshold metastatic disease outside of the treatment field does not eliminate the biochemical benefit of local therapy.

My problem with POP-RT is in the numbers themselves. These numbers are small to begin with and become quite small as the trial progresses. The censoring of the arms is not as expected by events and the events described are in my opinion "too good to be true". Fifteen to one pelvic failures with almost no biochemical failures without radiographically evident metastatic disease. Under what circumstance are almost all failures regional and manifested radiographically in the setting of PSA? Would you really expect 70% of high risk, high Gleason score prostate radiation only patients who progress to fail by radiographically evident pelvic disease and not by PSA?

 

[TheWallnerus]

I think I need a lesson on the significance of PSMA-PET.

My understanding was that PSMA-PET reveals PSMA-PET threshold metastatic disease ~30% of the time in high risk patients, changing treatment strategies in these patients (I know this is a gross generalization.) The argument here seems to be that by excluding these patients (well most patients got PSMA in POP-RT) only regionally advanced patients were included and that these patients derived maximum benefit from regional RT.

However, what would happen if you didn't exclude these patients? Well, here is what happened in Stampede Trial low metastatic burden patients with evident metastatic disease on standard imaging and treatment to the prostate only. These curves are driven by biochemical failures.

View attachment 331529
Here, it is clearly demonstrated that the presence of higher than PSMA threshold metastatic disease outside of the treatment field does not eliminate the biochemical benefit of local therapy.

My problem with POP-RT is in the numbers themselves. These numbers are small to begin with and become quite small as the trial progresses. The censoring of the arms is not as expected by events and the events described are in my opinion "too good to be true". Fifteen to one pelvic failures with almost no biochemical failures without radiographically evident metastatic disease. Under what circumstance are almost all failures regional and manifested radiographically in the setting of PSA? Would you really expect 70% of high risk, high Gleason score prostate radiation only patients who progress to fail by radiographically evident pelvic disease and not by PSA?

Werner Bezwoda says: “You ask too many questions.”

 

[evilbooyaa]

There is a bit of a logic flaw here with the weight given to the use of PSMA PETs in this study. You are arguing the key is their improved sensitivity to rule out patients with occult distant Mets who are unlikely to benefit from regional therapy. I can get behind you so far. Here is where it gets tricky. If regional nodal RT affords you a profound improvement over Prostate only RT in men who are N0 after PET staging, we have to conclude PETs are not good at detecting occult regional disease. If they were, regional RT wouldn’t be able to add much. So are we to conclude PSMAs are simultaneously great at detecting occult distant disease but crappy at detecting occult regional disease?

Look, a little cynicism is a good thing. Are there enough differences between this study and all of it’s predecessors to account for the differences in outcomes? Maybe. I just don’t personally find them compelling enough to say the issue is resolved and ignore mountains of earlier data. Like you said above, for most of us there is a continuum of when to include nodes. I suppose there are some people that always or never include nodes for high risk patients, but I have to assume more people are somewhere in the middle.

Regional RT is 45-50Gy and is likely not enough for gross nodal disease. Gross nodal disease was undercalled on CT scans in the past because of lack of sensitivity and use of size criteria for LNs. PSMA PET improves on identifying those with gross nodal disease that was previously occult.

I think terminology matters here - occult (IMO) is because the imaging study is not good enough, like CT and bone scan for nodal disease. I would call the POP-RT group to be at risk of having microscopic nodal disease (meaning no imaging study, ever, is going to be able to find it). This is too broad of a brush and there is some nuance, but just a concrete way to think about it with what we have right now.

If I had a patient who met inclusion criteria AND had a negative PSMA-PET, I would 100% treat LNs as per this trial. Given that the latter is NOT available in USA as of yet, it will always boil down to a discussion. Over half of the patients in that trial were VHR, which I would treat with nodal RT 100% of the time. They did see a uniform benefit regardless of HR vs VHR, but it's impossible to 'control' for the patients that were excluded to having a positive PSMA pet (the beignning of your first paragraph).

 

[ramsesthenice]

Regional RT is 45-50Gy and is likely not enough for gross nodal disease. Gross nodal disease was undercalled on CT scans in the past because of lack of sensitivity and use of size criteria for LNs. PSMA PET improves on identifying those with gross nodal disease that was previously occult.

I think terminology matters here - occult (IMO) is because the imaging study is not good enough, like CT and bone scan for nodal disease. I would call the POP-RT group to be at risk of having microscopic nodal disease (meaning no imaging study, ever, is going to be able to find it). This is too broad of a brush and there is some nuance, but just a concrete way to think about it with what we have right now.

If I had a patient who met inclusion criteria AND had a negative PSMA-PET, I would 100% treat LNs as per this trial. Given that the latter is NOT available in USA as of yet, it will always boil down to a discussion. Over half of the patients in that trial were VHR, which I would treat with nodal RT 100% of the time. They did see a uniform benefit regardless of HR vs VHR, but it's impossible to 'control' for the patients that were excluded to having a positive PSMA pet (the beignning of your first paragraph).

Terminology does matter and I think this is where we differ. What kind of distant disease do you think most people have? Most of them also have occult disease that the PET isn't going to pick up. The point I was making was I am unconvinced that PET-staging is doing as much to affect patient selection as you and others seem to think.

The much more plausible explanation is that what the PET-scans buy you has little to nothing to do with distant disease. I think where it much more likely to help you is to exclude patients who have macroscopic regional disease that wouldn't be adequately addressed with 45-50 Gy as you suggested. My suspicion has always been that the reason nodal RT fails it is isn't enough dose. If we really split hairs here the older studies were negative but close. The RTOG study showed an initial improvement in biochemical control that was lost over time. It does look like there is probably something there, just not enough. Whether it wasn't enough dose, we selected the wrong patients, or it just doesn't work we don't yet know. POP-RT strongly suggests the issue may have been patient selection. Like @communitydoc13 and @Chartreuse Wombat there are some specific issues with the data and design that give me pause from declaring this is it. I can't speak for others, but I think a better way of saying "too good to be true" is "too good to be repeated." That is too often the issue in all fields of medicine.

Fortunately, nodal RT is already an accepted SOC. People are free to practice how best they see fit based on their summary of the data. There are some things reasonable minds will just disagree on. Its when unreasonable minds (aka Evicore) get involved I want to rage.

 

[evilbooyaa]

Terminology does matter and I think this is where we differ. What kind of distant disease do you think most people have? Most of them also have occult disease that the PET isn't going to pick up. The point I was making was I am unconvinced that PET-staging is doing as much to affect patient selection as you and others seem to think.

The much more plausible explanation is that what the PET-scans buy you has little to nothing to do with distant disease. I think where it much more likely to help you is to exclude patients who have macroscopic regional disease that wouldn't be adequately addressed with 45-50 Gy as you suggested. My suspicion has always been that the reason nodal RT fails it is isn't enough dose. If we really split hairs here the older studies were negative but close. The RTOG study showed an initial improvement in biochemical control that was lost over time. It does look like there is probably something there, just not enough. Whether it wasn't enough dose, we selected the wrong patients, or it just doesn't work we don't yet know. POP-RT strongly suggests the issue may have been patient selection. Like @communitydoc13 and @Chartreuse Wombat there are some specific issues with the data and design that give me pause from declaring this is it. I can't speak for others, but I think a better way of saying "too good to be true" is "too good to be repeated." That is too often the issue in all fields of medicine.

Fortunately, nodal RT is already an accepted SOC. People are free to practice how best they see fit based on their summary of the data. There are some things reasonable minds will just disagree on. Its when unreasonable minds (aka Evicore) get involved I want to rage.

I think PSMA-PET is better at picking up macroscopic (meaning if you were physically in the belly you'd see or feel something off about the LN) disease that is otherwise occult because risk of overdiagnosis is too high (when evaluating LNs by CT for example) or the disease is in a location that simple CT and bone scan does not have the sensitivity necessary (like in bone, where one sees 'degenerative changes' on bone scan and 'bone islands' or 'subtle sclerosis felt to be reactive' on CT scan reports).

I think CT and bone scan were likely better than X-ray, and PSMA PET is simply the next thing that is better at identifying these areas on an imaging scan. I believe truly microscopic disease will not show up as positive. This is why (I think) sensitivity in the salvage setting is so low at low PSAs - not because there isn't anything there, but because the disease is microscopic in nature.

One thing we don't know is what number of patients were exlcuded by PSMA-PET prior to enrollment on trial because their PSMA-PET was positive.

I do understand the concern of 'too good to be repeated' which is true of most paradigm changing studies within all fields, especially oncology. I hope you're not SBRTing oligometastatic disease as per Gomez or SABR-COMET if you're sticking with the 'too good to be repeated' paradigm without phase III confirmatory data, as I would want you to be consistent in your thoughts about 'avoid treating by results that seem too good to be repeated, at least until the trial is repeated and confirmed'.

At end of the day, people are going to practice how they want. Without widespread adoption of PSMA-PET in the US, how to extrapolate these results really just ends up becoming dealer's choice, just like HR and VHR disease has always been.

The more we learn, the more things stay the exact same, and the more we end up with the exact same questions as we've always had. Mack Roach and Vedang Murthy - two brothers from separate mothers.

I don't think Evicore has started mandating when lymph nodes should be or should not be covered?

 

[ramsesthenice]

I don't think Evicore has started mandating when lymph nodes should be or should not be covered?

Of course not! But they are happy to mandate when we should do RT or not in plenty of other situations. I was implying at least this is a situation where either side of the fence is ok on that end.

 

[Chartreuse Wombat]

"I don't think Evicore has started mandating when lymph nodes should be or should not be covered?"

They are incentivizing pelvic LN treatment as they will allow >28 fractions only if treating the pelvis.

 

[ramsesthenice]

I do understand the concern of 'too good to be repeated' which is true of most paradigm changing studies within all fields, especially oncology. I hope you're not SBRTing oligometastatic disease as per Gomez or SABR-COMET if you're sticking with the 'too good to be repeated' paradigm without phase III confirmatory data, as I would want you to be consistent in your thoughts about 'avoid treating by results that seem too good to be repeated, at least until the trial is repeated and confirmed'.

Excellent points. I don't typically follow the SABR-COMET approach no but there are a lot of issues there that are pretty distinct from POP-RT. I think a more relevant comparison to POP-RT is probably ASCEND-RT. I do believe in using a brachy boost for people with high volume high risk disease and I do it. But not because of the trial. I am still a bit skeptical there will be a significant improvement in distant disease control or survival with longer follow up. But, I do think you get better in gland control and as long as you are using HDR toxicity really is not an issue. Since in gland failures can be fairly disastrous there is a clinical rationale to do it even if longer term oncologic outcomes don't pan out. Note the calculation: risk/benefit. I can easily understand who people who have only done LDR or have not done much brachy would look at the data and reach a different conclusion.

 

[evilbooyaa]

"I don't think Evicore has started mandating when lymph nodes should be or should not be covered?"

They are incentivizing pelvic LN treatment as they will allow >28 fractions only if treating the pelvis.

I have read about this but have not had it affect my practice as of yet. I would hope that a discussion of 'Patient was educated about higher risk of acute GI toxicity with a mod hypo regimen as per most recent consensus guidelines and chose the longer option' would suffiice on a p2p.

The one patient I've done conventional included LN coverage, I suppose.

 

[evilbooyaa]

Excellent points. I don't typically follow the SABR-COMET approach no but there are a lot of issues there that are pretty distinct from POP-RT. I think a more relevant comparison to POP-RT is probably ASCEND-RT. I do believe in using a brachy boost for people with high volume high risk disease and I do it. But not because of the trial. I am still a bit skeptical there will be a significant improvement in distant disease control or survival with longer follow up. But, I do think you get better in gland control and as long as you are using HDR toxicity really is not an issue. Since in gland failures can be fairly disastrous there is a clinical rationale to do it even if longer term oncologic outcomes don't pan out. Note the calculation: risk/benefit. I can easily understand who people who have only done LDR or have not done much brachy would look at the data and reach a different conclusion.

To me, the difference is that nobody doesn't believe the bPFS benefit seen in ASCENDE-RT (meaning, everybody believes the bPFS benefit). There are just strong arguments on either side of *whether* bPFS matters in the setting of that treatment scenario without a difference in PCSM/OS. Nobody is saying "Brachy boost does NOT provide a bPFS benefit in the patient population ASCENDE-RT studied!!"

What we have with POP-RT is people just completely dismissing the data (nodal RT does NOT improve OS in this specific patient population!) only because it doesn't go along with their own convictions. Those who don't treat LNs routinely see it as too good to be repeated and come up with whatever hand-wringing necessary to continue as they always have.

Those who do LNs see it as vindication of their practice after the assaults on nodal RT for the past 20 years.

But, people compare it to other trials evaluating HR patients like 9413 and miss so much that is different.

 

[medgator]

"I don't think Evicore has started mandating when lymph nodes should be or should not be covered?"

They are incentivizing pelvic LN treatment as they will allow >28 fractions only if treating the pelvis.

Despite what is clearly stated in ASTROs guidelines about moderate hypofx vs conventional in terms of acute toxicity... I actually was able to get conventional approved (pt requested) through a third party appeal via the payor when evicore only approved hypofx and i sent those guidelines in as part of it

 

[FrostyHammer]

Nobody is saying "Brachy boost does NOT provide a bPFS benefit in the patient population ASCENDE-RT studied!!"

Well, I'm not sure I believe even the bPFS benefit in high risk patients... The p value was barely significant, and the ADT was inadequate for high risk patients. Would it still have been significant if adequate ADT would be given? That's the unresolved question.

 

[ramsesthenice]

after the assaults on nodal RT for the past 20 years.

By assaults you mean multiple negative trials?

We are obviously just going to be far apart on this and that is cool. I find it interesting you bring up the convictions of people who question POP-RT when you were regularly treating nodes despite multiple negative trials on the topic prior to this publication. I don't doubt POP Rt because of my convictions. I doubt the robustness because of all the negative data that came before it. If this were the first, or even second nodal RT trial ever attempted I would not feel this way. Again, I know we don't see eye to eye on this one but I am not sold that the methodological differences are that substantial.

 

[evilbooyaa]

By assaults you mean multiple negative trials?

We are obviously just going to be far apart on this and that is cool. I find it interesting you bring up the convictions of people who question POP-RT when you were regularly treating nodes despite multiple negative trials on the topic prior to this publication. I don't doubt POP Rt because of my convictions. I doubt the robustness because of all the negative data that came before it. If this were the first, or even second nodal RT trial ever attempted I would not feel this way. Again, I know we don't see eye to eye on this one but I am not sold that the methodological differences are that substantial.

I don't treat nodes on most HR patients. I usually need the Partin nomogram to tell me it's like above like 35-50% for it to be a 'slam dunk' on telling patient they need nodes treated (and even that isn't evidence based), and if it's questionable (say 20-35%), I usually do shared decision making. Less than 20% I usually don't even mention nodes beyond a cursory "some would suggest treating LNs, but a trial (9413) told us that wasn't necessary".

My 'those' earlier was more of a general 'those', not 'those including myself who practice like this, how dare you question my practice!!'

I'm not going to be treating LNs in all HR patients even with POP-RT results, because I don't have access to PSMA PET. All I'm saying, is that if/when I do get full access to PSMA PET-staging, I will act as per the POP-RT trialists and include LNs for all HR patients.

I do treat LNs in all VHR patients.

That being said, we will have to agree to disagree on the bolded, because to me, nothing else makes sense as to why they would see those results.

Let's get on the same side by going off on a related tangent - some people treat LNs in some subset of UIR patients, and those people I just don't get at all.

Well, I'm not sure I believe even the bPFS benefit in high risk patients... The p value was barely significant, and the ADT was inadequate for high risk patients. Would it still have been significant if adequate ADT would be given? That's the unresolved question.

OK.

 

[ramsesthenice]

I don't treat nodes on most HR patients. I usually need the Partin nomogram to tell me it's like above like 35-50% for it to be a 'slam dunk' on telling patient they need nodes treated (and even that isn't evidence based), and if it's questionable (say 20-35%), I usually do shared decision making. Less than 20% I usually don't even mention nodes beyond a cursory "some would suggest treating LNs, but a trial (9413) told us that wasn't necessary".

My 'those' earlier was more of a general 'those', not 'those including myself who practice like this, how dare you question my practice!!'

I'm not going to be treating LNs in all HR patients even with POP-RT results, because I don't have access to PSMA PET. All I'm saying, is that if/when I do get full access to PSMA PET-staging, I will act as per the POP-RT trialists and include LNs for all HR patients.

I do treat LNs in all VHR patients.

That being said, we will have to agree to disagree on the bolded, because to me, nothing else makes sense as to why they would see those results.

Let's get on the same side by going off on a related tangent - some people treat LNs in some subset of UIR patients, and those people I just don't get at all.



OK.

All said and done, sounds like we practice more or less the same. You are always very thoughtful and well spoken on your practice and the literature. Nothing but love 🙂

 

[communitydoc13]

What we have with POP-RT is people just completely dismissing the data (nodal RT does NOT improve OS in this specific patient population!) only because it doesn't go along with their own convictions. Those who don't treat LNs routinely see it as too good to be repeated and come up with whatever hand-wringing necessary to continue as they always have.

I treat with ENI in high risk patients. I'd probably offer ENI to the vast majority of the patients in POP-RT. I'm confident that it provides a bPFS benefit. I'm also impressed by the SPPORT data. I think there is real toxicity to salvage therapy in the biochemical progression setting and the decision making in that scenario is very difficult. The toxicity of pelvic nodal radiation is not comparable to brachy boost. (I concede that a killer HDR program may make things different.)

Regarding POP-RT, the numbers are just small and weird, as discussed above. The statistics of small numbers are critical. P-values are just not that valuable when it comes to small trials. It is a bad trial and it is a shame that name brand radoncs didn't question this. (Maybe they did?) There are numerous aspects of their results that beg the question of reproducibility and are counterintuitive. (Counterintuitive is important, particularly if you are thinking in a Bayesian kind of way.) It is now a JCO paper so I got to read it.

Of concern:

1. almost nobody failed in the pelvic arm and total events were roughly 30% of what they predicted and what went into their power calculations

2. preferential pelvic failures with nearly no local failures when to my knowledge local failure is a predominant finding by PSMA-PET with biochemical failure after XRT

3. No quantification of PSMA restaging (I'm guessing must be close to 100%, because biochemical failure alone very rare in their cohort and traditional imaging not going to reveal disease in 90+ percent of PSA failures)

4. MOST IMPORTANTLY. Peculiarities in data with time (the number at risk are closely balanced between arms despite disparities in failures). This is very counterintuitive (the arm with more events should have a roughly proportional decrease in number at risk as time goes forward). They quote a median f/u of 68 months but very few patient with events after this time point and very few evaluable patients despite a 9 year trial run. (These peculiarities could be partially explained if there was a stagger in enrollment between the arms and nearly no one enrolled early in the trial.)

The arguments regarding PSMA finding just the right patients for POP-RT are interesting. I think @ramsesthenice alludes to this above. There is still plenty of micometastatic disease in very high risk PSMA negative patients and local management of any sort seems to impact natural history of limited burden metastatic disease (as demonstrated in Stampede). The idea that we cover all micrometastatic disease ever is probably antiquated.

If I was confident in POP-RT it wouldn't change my practice a bit. I can't get a PSMA PET locally and I do Axumin on occasion in setting of biochemical failure. I just don't like the rare RT trial in JCO being like this. The non-skeptical congratulations by prominent GU radoncs in the public sphere is concerning to me. Maybe I'm just not aware of push back.

As an aside. In my opinion, there is a peculiar irony of prostate cancer data that goes back a long time. The patients that you are least likely to cure (or at least obtain durable PSA control on) are the ones you are most likely to impact in terms of overall survival outcomes with XRT. Even before Stampede, this was evident in salvage data going way back (look at old Trock salvage paper from 2008). This holds to a limit, obviously high metastatic burden patients are not benefiting from local XRT.

 

[DoctwoB]

We don’t get many. Almost all of the older patients opt for AS with urology and that is that. We mostly get younger patients who refuse surgery or people who want treatment and know someone who either had a good experience with RT or a bad experience with surgery. Typically they had a dad or uncle who got “seed treatment” and had no trouble. Or they had surgery and piss a little every time they swing too hard with the driver ☹️

Not urology bashing here. My best friend is a urologist and they get the opposite patients too.

My AS uptake rates are very high. Almost too high. Some of the low volume GG2 patients who I bring it up as an option that I try to steer them away from jump all over it.

You are right though when it comes to surgery vs radiation you’ll never make an argument more convincing then “my uncle(friend, dad, etc) had X and did great (or horrible) so I want (or don’t want) that.

 

[medgator]

You are right though when it comes to surgery vs radiation you’ll never make an argument more convincing then “my uncle(friend, dad, etc) had X and did great (or horrible) so I want (or don’t want) that.

Yup! Just saw a self referral who pissed off the high volume robotic guy by refusing rp... Can't blame him though, older with a psa of 45, high volume G8 whose buddy had a good experience with radiation...

 

[ramsesthenice]

My AS uptake rates are very high. Almost too high. Some of the low volume GG2 patients who I bring it up as an option that I try to steer them away from jump all over it.

You are right though when it comes to surgery vs radiation you’ll never make an argument more convincing then “my uncle(friend, dad, etc) had X and did great (or horrible) so I want (or don’t want) that.

The conversation for GG1-2 is slightly different for us than you. If someone knows they want surgery no matter what the treatment won’t change if they progress to a higher risk group. If they are dead set against surgery and know they will go the RT route we have to talk a bit more about options because I can’t offer Brachy as a monotherapy for higher risk groups. I always stress that it’s (probably) no more effective than EBRT or combo options so I am completely fine with AS. But if they are specifically looking for it, and a decent number of folks are, it may be worth thinking about treatment now (assuming they have a decent life expectancy of course). For GG2 patients there is also the issue of ADT. Can avoid it now, but go any further and you will need it. That is a deal breaker for some guys. No matter how many different ways you try to explain you won’t have any sex drive, the thought of not being able to get an erection is truly unacceptable.

 

[DoctwoB]

The conversation for GG1-2 is slightly different for us than you. If someone knows they want surgery no matter what the treatment won’t change if they progress to a higher risk group. If they are dead set against surgery and know they will go the RT route we have to talk a bit more about options because I can’t offer Brachy as a monotherapy for higher risk groups. I always stress that it’s (probably) no more effective than EBRT or combo options so I am completely fine with AS. But if they are specifically looking for it, and a decent number of folks are, it may be worth thinking about treatment now (assuming they have a decent life expectancy of course). For GG2 patients there is also the issue of ADT. Can avoid it now, but go any further and you will need it. That is a deal breaker for some guys. No matter how many different ways you try to explain you won’t have any sex drive, the thought of not being able to get an erection is truly unacceptable.

Good point, and one that I should probably raise more. Would also be interested to see if there is data for higher rates of salvage xrt for delayed treatment rather then up front for GG2, which wouldn’t surprise me.

I’m not a huge fan of AS for GG2 in general, rates of progression to active treatment extremely high and rates of progression to Mets low but higher then I’m comfortable with. I only really push it for the men who are on the borderline of treatment vs watchful waiting and only need true surveillance for a few years.

Incidentally this is the one area where I could see focal therapy playing a role, which I’m not too optimistic about in general. Not so much as a “definitive treatment” but as a way of lowering progression to active treatment on AS from 50-60% to something lower.

 

[evilbooyaa]

Good point, and one that I should probably raise more. Would also be interested to see if there is data for higher rates of salvage xrt for delayed treatment rather then up front for GG2, which wouldn’t surprise me.

I’m not a huge fan of AS for GG2 in general, rates of progression to active treatment extremely high and rates of progression to Mets low but higher then I’m comfortable with. I only really push it for the men who are on the borderline of treatment vs watchful waiting and only need true surveillance for a few years.

Incidentally this is the one area where I could see focal therapy playing a role, which I’m not too optimistic about in general. Not so much as a “definitive treatment” but as a way of lowering progression to active treatment on AS from 50-60% to something lower.

I hate AS for GG2/Gleason 3+4=7 (I hate the name GG btw, but am trying to be more open for change)

I just hate all focal therapies. Prove it has a benefit without insane toxicity and then let's go ahead and move forward. All the publications have crazy bad control rates and/or crazy bad toxicity compared to SOC