Stampede: RT for M1 PCA—> OS benefit

[Palex80]

ESMO | Press Release | STAMPEDE prostate radiotherapy Parker | ESMO

11% OS benefit and HR of 0.68 (Abi was 0.63) for patients with limited mets.

Game changer!

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[thecarbonionangle]

Can we create just one post for anything important to know out of Astro/esmo? Post big studies please

 

[MegaVoltagePhoton]

Can we create just one post for anything important to know out of Astro/esmo? Post big studies please

Disagree. Then major findings will get diluted and sidetracked. It's not like this board has a million active topics, not hard to follow the major updates.

 

[Palex80]

Full paper published in the Lancet (open access):

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32486-3/fulltext

 

[thaddeus]

Full paper published in the Lancet (open access):

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32486-3/fulltext

The skeptic (read: med onc) may note that the trial was negative for its primary endpoint, and the OS benefit was only seen on exploratory subgroup analysis for patients with limited mets. In my mind, this data is enough to recommend RT in patients with limited mets, but don't expect the referrals to come rushing in. Will be interesting to see whether NCCN incorporates this data.

 

[MegaVoltagePhoton]

The skeptic (read: med onc) may note that the trial was negative for its primary endpoint, and the OS benefit was only seen on exploratory subgroup analysis for patients with limited mets. In my mind, this data is enough to recommend RT in patients with limited mets, but don't expect the referrals to come rushing in. Will be interesting to see whether NCCN incorporates this data.

They're prespecified, though, and the interaction term is highly significant. That's very different than an exploratory post-hoc analysis.

 

[MegaVoltagePhoton]

"Our subgroup finding meets all criteria proposed by Sun and colleagues to assess credibility of subgroup effects: low metastatic burden status was determined from scans taken before randomisation; the hypothesis—including the direction of the effect—was specified a priori; only a few hypothesised subgroup effects were tested; the interaction test suggested a low likelihood that the apparent subgroup effect could be accounted for by chance; the subgroup effect was independent of other assessed variables; the size of the subgroup effect was large (HR 0·68 for low metastatic burden and HR 1·07 high metastatic burden); and the interaction was consistent both with other related outcome measures in STAMPEDE (eg, failure-free survival) and with the interaction reported on number of bone metastases in the HORRAD trial (less than five bone metastases, HR 0·68; five or more bone metastases, HR 1·06). It also seems plausible that the effect of local radiotherapy would be diminished in patients with a greater burden of metastatic disease. There is, therefore, good reason to accept that prostate radiotherapy improves survival of men with a low metastatic burden and that it should now be a standard treatment. Unlike many other new interventions for metastatic cancer, prostate radiotherapy does not require regulatory approval and is readily available at modest cost in most parts of the world."

 

[seper]

I wonder what that means for ultra-high risk localized prostate cancer (e.g. GS 8, PSA 50). I'm usually hesitant to radiate thinking it is futile.

 

[BobbyHeenan]

...So in light of Stampede and SABR-COMET....

You've got a guy with prostate cancer with two asymptomatic bone mets.

You radiating just the prostate or the bone mets too with SABR?

 

[ramsesthenice]

...So in light of Stampede and SABR-COMET....

You've got a guy with prostate cancer with two asymptomatic bone mets.

You radiating just the prostate or the bone mets too with SABR?

In my part of the country that is not really the important question. I have slowly convinced the urologists and the other radiation oncologists at my institution that we should be more aggressive treating the prostate in patients who present with limited metastatic disease. People used to laugh at me and say that the NCDB and QOL analyses were biased and flawed. But my practice for years has been to do a 3-4 month test of ADT. If they have a good response then it is obvious to me that local control of the primary is a big deal. Suprapubic catheters, perforated rectums...none of these things are pleasant and we have all seen them when neglected primaries are allowed to grow unchecked.

In my mind, the biggest thing to come out of this study isn't that we should be treating the mets, its that it confirms that we should be aggressively treating the primary tumor.

 

[medgator]

I wonder what that means for ultra-high risk localized prostate cancer (e.g. GS 8, PSA 50). I'm usually hesitant to radiate thinking it is futile.

I've treated a guy with Gleason 9 and psa 223 with +nodes and negative scans at Dx several years ago with 28 months of adt. He's now >5 years out, ned, psa undetectable. Sometimes it's the regional nodes making that high psa

 

[ramsesthenice]

I wonder what that means for ultra-high risk localized prostate cancer (e.g. GS 8, PSA 50). I'm usually hesitant to radiate thinking it is futile.

Im with Gator. I have more than a handful of these cases that have turned out well. The people that scare me are the ones with a higher GS than PSA.

I would also question what you think is futile? I presume your assumption is that they will eventually met out and you don't think they would benefit from the radiation to the prostate. If they are not castrate resistant they will probably live more than long enough to get into trouble from local progression. Multiple institutional and population-based studies have convincingly shown that definitive dosing to the prostate probably improves QOL for patients with low burden metastatic disease. At least one NCDB showed that surgery and RT were both associated with improved OS. People appropriately argued that reflected selection bias and to some extent it had to. But if you think about it, is it that crazy of a thought? Cytoreductive surgery improves OS for patients with metastatic RCC. Why is it so far fetched that definitive RT or surgery could improve OS for low-burden metastatic prostate cancer patients?

The other question I would have is what is the alternative? Do you think they are better off getting surgery and save radiation for a salvage option? If your concern is they are high risk for distant failure I think it is hard to argue the specific modality chosen for local therapy is going to matter. Heck, at least with RT they would be getting ADT and some form of systemic therapy upfront.

 

[thaddeus]

They're prespecified, though, and the interaction term is highly significant. That's very different than an exploratory post-hoc analysis.

Totally agree on the merits. Just making the point that many med oncs will read the read the one-line interpretation of the study and conclude it was a negative trial, without getting into the weeds of the subgroup analysis and whether it was prespecified. It is incumbent on us to promote this study to our colleagues and make sure everyone is aware of the results for properly selected patients.

 

[thecarbonionangle]

Disagree. Then major findings will get diluted and sidetracked. It's not like this board has a million active topics, not hard to follow the major updates.

Megavoltagephoton has spoken. MY BAD.

 

[Palex80]

Interstingly in the full paper the authors note that symptomatic local progression was the same among the two groups (those with RT or not).
Symptomatic progression is of course not the same as progression per se, but: Stampede is probably the randomized large phase III trial pointing out that treating the primary tumor in the metastatic setting with RT can alter the course of the disease. Pretty much what the surgeons had with nephrectomy for two decades (although their evidence was clearly less solid and the reason why everyone got nephrectomy for metastatic RCC had also to do with the fact that the med-oncs pretty much had nothing to treat metastatic RCC with...)

What we are seeing in STAMPEDE is possibly through
a) inhibition of further microseeding from the primary or
b) killing off more aggressive subparts of the tumor that area already present in the prostate (think of small cell / neuroendocrine subtypes of PCA, which pop up later during the course of the disease and are resistant to ADT) or
c) mediating the "famous" abscopal effect of RT

A nice side "gain" for us as radiation oncologists from this trial IMHO will pop up 3-5 years from now. By then pretty much every PCA patient will PSMA-PET-CT from primary staging if they have high-risk localized disease. A sizable amount of these patients will then be upstaged to metastatic in lymph nodes or bones or whatever. Mets will pop up that were not visible on "classic" CT-staging.
The surgeons WILL NOT have a randomized trial by then showing a benefit through surgery, so what's left? RT. And since 55 / 2.75 is not that far off from 60 / 3, we may as well treat those patients with hypofractionated RT, which will by then be s.o.c.

 

[MegaVoltagePhoton]

Megavoltagephoton has spoken. MY BAD.

wasn't trying to be a dick dude. Just saying, easier to segregate topics. look how much discussion just stampede and sabr-comet respectively generated....

 

[seper]

Yes, my thinking used to be that very high risk prostate cancer always has undetectable metastases, and they will invariably fail after local therapy (prostatectomy data). Dose escalation that my group uses (brachy or 80 Gy) is toxic. Why take a risk of radiation cystitis if mets will happen anyway? STAMPEDE data changes this logic IMO.

Im with Gator. I have more than a handful of these cases that have turned out well. The people that scare me are the ones with a higher GS than PSA.

I would also question what you think is futile? I presume your assumption is that they will eventually met out and you don't think they would benefit from the radiation to the prostate. If they are not castrate resistant they will probably live more than long enough to get into trouble from local progression. Multiple institutional and population-based studies have convincingly shown that definitive dosing to the prostate probably improves QOL for patients with low burden metastatic disease. At least one NCDB showed that surgery and RT were both associated with improved OS. People appropriately argued that reflected selection bias and to some extent it had to. But if you think about it, is it that crazy of a thought? Cytoreductive surgery improves OS for patients with metastatic RCC. Why is it so far fetched that definitive RT or surgery could improve OS for low-burden metastatic prostate cancer patients?

The other question I would have is what is the alternative? Do you think they are better off getting surgery and save radiation for a salvage option? If your concern is they are high risk for distant failure I think it is hard to argue the specific modality chosen for local therapy is going to matter. Heck, at least with RT they would be getting ADT and some form of systemic therapy upfront.

 

[ramsesthenice]

Yes, my thinking used to be that very high risk prostate cancer always has undetectable metastases, and they will invariably fail after local therapy (prostatectomy data). Dose escalation that my group uses (brachy or 80 Gy) is toxic. Why take a risk of radiation cystitis if mets will happen anyway? STAMPEDE data changes this logic IMO.

Sounds reasonable. I have been doing hypofrac for these guys (2.5 to 70) so that they are not getting palliative RT for 2 months. I really don't see much toxicity with this so I like to think that I help more people than I hurt. I can see where you were coming from. I hope more people have a similar interpretation of STAMPEDE.

 

[evilbooyaa]

Can we create just one post for anything important to know out of Astro/esmo? Post big studies please

I think having a specific thread for each big study is beneficial, because it keeps discussions on-topic.

...So in light of Stampede and SABR-COMET....

You've got a guy with prostate cancer with two asymptomatic bone mets.

You radiating just the prostate or the bone mets too with SABR?

Yes. Everything. I have to read the SABR-COMET protocol at some point, but at least for the Gomez trial, the primary needed to have definitive treatment (either surgery, SBRT, or hypofractionated 45-60/15) as well.


I agree that if you're treating metastatic disease, hypofrac to the primary. I think what we're seeing is preventing re-seeding of mets from the large primary.

OK - read through the SABR-COMET trial protocol (Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): Study protocol for a randomized phase II trial) - The primary had to be controlled with treatment at least 3 months ago, so it couldn't be newly diagnosed oligometastatic patients. But yes, per STAMPEDE and SABR COMET, I'd argue there's a benefit of definitively treating everything you see in an oligometastatic prostate/lung/CRC patient.

 

[Haybrant]

From what I understand sabr-comet is patients who developed distant oligomet recurrence after primary therapy that was initially thought to be curative. Gomez on the other hand was metastatic at prez and you started with chemo then decided how to act. Fundamentally these are different patient groups. Tbh I think the Gomez population is a bit more of a reach but ya it seemed to have worked. Also I think all brain mets are considered a single site so it’s not like 2 brain mets are 2 sites.

 

[evilbooyaa]

From what I understand sabr-comet is patients who developed distant oligomet recurrence after primary therapy that was initially thought to be curative. Gomez on the other hand was metastatic at prez and you started with chemo then decided how to act. Fundamentally these are different patient groups. Tbh I think the Gomez population is a bit more of a reach but ya it seemed to have worked. Also I think all brain mets are considered a single site so it’s not like 2 brain mets are 2 sites.

You're mostly correct in regards to oligorecurrent in SABR COMET vs upfront oligometastatic (or more precisely, up to 3 sites of active metastatic disease after chemo, meaning they could've started with 5+ but if they had a complete response to chemo that's cool) .

However, in regards to the bolded, each brain met was counted as individual lesion. Gomez allowed those to be treated prior to chemo, but they counted towards the total number of 3 (meaning if you SRS'd 2 brain mets prior to chemo, you could only have one active site of metastatic disease after chemo to be eligible). SABR COMET just had a limitation of no more than 3 lesions in one organ (lung, brain, liver, etc.), but each lesion counted towards the relevant number.

 

[Haybrant]

You're mostly correct in regards to oligorecurrent in SABR COMET vs upfront oligometastatic (or more precisely, up to 3 sites of active metastatic disease after chemo, meaning they could've started with 5+ but if they had a complete response to chemo that's cool) .

However, in regards to the bolded, each brain met was counted as individual lesion. Gomez allowed those to be treated prior to chemo, but they counted towards the total number of 3 (meaning if you SRS'd 2 brain mets prior to chemo, you could only have one active site of metastatic disease after chemo to be eligible). SABR COMET just had a limitation of no more than 3 lesions in one organ (lung, brain, liver, etc.), but each lesion counted towards the relevant number.

Thanks evilB, good info. Just to clarify in sabr comet what do you mean the limitation was no more than 3 lesions in one organ, Like if you have 4 lung mets then you are disqualified? But in total you could have up to 5 mets throughout the body to be on protocol? I know overall tho they said majority had 1-2 mets.

Also I had a head and neck discussed in Tumor board that got definitive chemo/rt hpv+ then 6 months later came back with like 9 lung mets. Nothing right now would say ok put him on chemo or immuno and if he has a great response with just 3 mets remaining that we should consider giving him sbrt?

 

[evilbooyaa]

Exactly. The protocol says you could have say 2 lung and 2 liver mets, but not 4 lung mets.

The real data is for 1-3 mets. The number of patients who had 4 or 5 mets was incredibly low and I wouldn't directly use SABR-COMET to justify anything unless I was treating 3 or less given that the trial didn't have any real perecentage of patients who had 4 or 5 mets. SABR COMET 10 (phase III they are starting) will evaluate 4-10 oligomets and SBRTing everything.

 

[Haybrant]

Anyone talking about how this data somewhat does vindicate the urologists? Over the last year I’ve been more appreciative of young guys going to surgery for high risk disease. The reason is that after I give them RT and they recur the young guys are in a pretty terrible situation esp when they have local/regional recurrence

 

[seper]

I disagree. 55 Gy of XRT is pretty non-consequential but prostatectomy mutilates a fair amount of patients.

Anyone talking about how this data somewhat does vindicate the urologists? Over the last year I’ve been more appreciative of young guys going to surgery for high risk disease. The reason is that after I give them RT and they recur the young guys are in a pretty terrible situation esp when they have local/regional recurrence

 

[evilbooyaa]

Anyone talking about how this data somewhat does vindicate the urologists? Over the last year I’ve been more appreciative of young guys going to surgery for high risk disease. The reason is that after I give them RT and they recur the young guys are in a pretty terrible situation esp when they have local/regional recurrence

I think comparing oligometastatic and non-metastatic high risk are completely different question. I'm not sure what in this data suggests prostatectomy is better than RT. I'm not aware of any data suggesting that patients who get prostatectomy with or without adjuvant or salvage RT do better than patients getting definitive RT + ADT.

The main thing the urologists are going to extrapolate this to, IMO, is doing prostatectomy in oligometastatic prostate cancer. "Since RT is clearly inferior (in their opinion) and definitive local therapy to the prostate improves survival in oligometastatic, clearly the best (citation needed) local therapy will improve survival. Clearly"

 

[Chartreuse Wombat]

I think comparing oligometastatic and non-metastatic high risk are completely different question. I'm not sure what in this data suggests prostatectomy is better than RT. I'm not aware of any data suggesting that patients who get prostatectomy with or without adjuvant or salvage RT do better than patients getting definitive RT + ADT.

The main thing the urologists are going to extrapolate this to, IMO, is doing prostatectomy in oligometastatic prostate cancer. "Since RT is clearly inferior (in their opinion) and definitive local therapy to the prostate improves survival in oligometastatic, clearly the best (citation needed) local therapy will improve survival. Clearly"

From the discussion of the STAMPEDE paper...
"It is possible that other forms of local treatment—such as radical prostatectomy—might also be effective. If the benefit of radiotherapy is mediated by local tumour eradication, one would expect surgery to be at least as effective. However, radiotherapy might be effective via other mechanisms (eg, immune modulation), so the role of surgery in men with metastatic prostate cancer remains unproven. The feasibility of prostate surgery in this setting is being tested in the g-RAMMP trial (NCT02454543) and the TROMBONE feasibility study."
Of course if you don't need evidence and can't read then the point is moot.

 

[evilbooyaa]

From the discussion of the STAMPEDE paper...
"It is possible that other forms of local treatment—such as radical prostatectomy—might also be effective. If the benefit of radiotherapy is mediated by local tumour eradication, one would expect surgery to be at least as effective. However, radiotherapy might be effective via other mechanisms (eg, immune modulation), so the role of surgery in men with metastatic prostate cancer remains unproven. The feasibility of prostate surgery in this setting is being tested in the g-RAMMP trial (NCT02454543) and the TROMBONE feasibility study."

Of course if you don't need evidence and can't read then the point is moot.

My personal experience with urologists is generally the bolded, FWIW.

 

[Haybrant]

.

 

[Haybrant]

I think comparing oligometastatic and non-metastatic high risk are completely different question. I'm not sure what in this data suggests prostatectomy is better than RT. I'm not aware of any data suggesting that patients who get prostatectomy with or without adjuvant or salvage RT do better than patients getting definitive RT + ADT.

The main thing the urologists are going to extrapolate this to, IMO, is doing prostatectomy in oligometastatic prostate cancer. "Since RT is clearly inferior (in their opinion) and definitive local therapy to the prostate improves survival in oligometastatic, clearly the best (citation needed) local therapy will improve survival. Clearly"

Yes I know there is nothing in the study to suggest that. But do you really believe this has nothing to do with local control. It should give one pause to think what the surgeons are saying has some validity. In a pt w very high risk dz removing the prostate provides a benefit. If you see the young guys that recur locally after radiation and the world of hurt they are in and the morbidity that they experience at attempts at local control it makes more sense. Now this data shows survival benefit to local RT in pts w mets. If the patients w mets or oligomets are on the same continuum then don’t be surprised if their studies show benefit to high risk patients and that does become soc for young pts w very high risk dz

 

[Palex80]

Yes I know there is nothing in the study to suggest that. But do you really believe this has nothing to do with local control. It should give one pause to think what the surgeons are saying has some validity. In a pt w very high risk dz removing the prostate provides a benefit. If you see the young guys that recur locally after radiation and the world of hurt they are in and the morbidity that they experience at attempts at local control it makes more sense. Now this data shows survival benefit to local RT in pts w mets. If the patients w mets or oligomets are on the same continuum then don’t be surprised if their studies show benefit to high risk patients and that does become soc for young pts w very high risk dz

Local control is not the "driver" for the OS benefit shown in Stampede. In fact both patient groups (with/without RT) experienced the same rates of local progression requiring intervention, mostly TUR-P.
Two effects are the driver:
1. Killing of ADT-resistant cell subpopulations in the prostate (surgery can do the same by removing them).
2. Abscopal (surgery can't do that).

 

[Haybrant]

Local control is not the "driver" for the OS benefit shown in Stampede. In fact both patient groups (with/without RT) experienced the same rates of local progression requiring intervention, mostly TUR-P.
Two effects are the driver:
1. Killing of ADT-resistant cell subpopulations in the prostate (surgery can do the same by removing them).
2. Abscopal (surgery can't do that).

How can you say abscopal effect? Was there some difference between the sbrt and hypofrac arm? We’re these people not on systemic therapy? Also even if the rates of TURP ultimately were the same the timing was different

 

[Palex80]

How can you say abscopal effect? Was there some difference between the sbrt and hypofrac arm? We’re these people not on systemic therapy? Also even if the rates of TURP ultimately were the same the timing was different

I was referring to STAMPEDE. RT to the prostate may have unleashed an abscopal effect.

 

[Haybrant]

I was referring to STAMPEDE. RT to the prostate may have unleashed an abscopal effect.

Also referring to stampede. What in the results even minimally suggests abscopal effect? If there is a difference bt the sbrt arm and more prolonged course arm then maybe there is something to that. Are the authors claiming abscopal effect?

 

[Palex80]

Also referring to stampede. What in the results even minimally suggests abscopal effect? If there is a difference bt the sbrt arm and more prolonged course arm then maybe there is something to that. Are the authors claiming abscopal effect?

I am sorry, but the 6 x 6 Gy arm once per week was not SBRT. This is a British trial. The 6 x 6 Gy was planned and executed just like the 55 / 2.75 arm, merely dose per day and fractionatio were altered.

The abscopal effect can of course not be proven but it's one of the possible explanations why the trial turned out positive. I am not claiming that all the benefit resulted from an abscopal effect, however part of it may have.
And this is what surgery cannot deliver.

 

[RO2019]

We shouldn’t bring up abscopal because the study was not at all designed to show it. Abscopal is a very specific definition - that other areas of disease got smaller after treating the primary.

The much more clear explanation for less distant disease (both here or in the Gomez and COMET studies) is that by destroying areas of known disease, there is then less disease to go and seed other metastatic sites.

 

[ramsesthenice]

Yes I know there is nothing in the study to suggest that. But do you really believe this has nothing to do with local control. It should give one pause to think what the surgeons are saying has some validity. In a pt w very high risk dz removing the prostate provides a benefit. If you see the young guys that recur locally after radiation and the world of hurt they are in and the morbidity that they experience at attempts at local control it makes more sense. Now this data shows survival benefit to local RT in pts w mets. If the patients w mets or oligomets are on the same continuum then don’t be surprised if their studies show benefit to high risk patients and that does become soc for young pts w very high risk dz

You could be right but you are making a few assumptions. Even the most pro-surgery papers consistently show that biochemical failure or need for secondary treatment is higher for patients treated with upfront surgery. This is usually buried and you have to dig for the data, but it is there. This somewhat undermines the argument that at least with surgery we have a salvage option. Thats good to know because they are also more likely to need it. While guys with a local failure after RT end up in a world of hurt and you probably are helping some of them with upfront surgery, we also know they are a minority of patients and we can say with near 100% confidence that post-op RT greatly increases the incidence of long-term symptomatic toxicity compared to either modality alone. I can see where you are coming from but I am concerned this logic is setting a lot of men up for multimodality treatment and there is a real chance the balance of people helped vs people hurt may not be favorable as you think.

All that being said, its still fair to say we dont' know which, if either, is the better treatment. Its a very personal choice with pro's and con's to each. Everyone, even physicians, are entailed to their own opinions as long as they are not dependent upon exceptionally flawed data or based on demonstrably false claims.

 

[Palex80]

We shouldn’t bring up abscopal because the study was not at all designed to show it. Abscopal is a very specific definition - that other areas of disease got smaller after treating the primary.

Abscopal can also happen in the microscopic level. You do not need to "see" remission of a metastatic site on imaging because of an abscopal effect.
Abscopal effect can also mean that a collection of 100 cells, which are going to become a visible metastasis "down the road" are being eradicated by the immune system because you treated either the primary or some other metastatic site.

The much more clear explanation for less distant disease (both here or in the Gomez and COMET studies) is that by destroying areas of known disease, there is then less disease to go and seed other metastatic sites.

Says who? Can you prove it? It could also be abscopal as well.


Actually one way of finding this would be to look into patterns of progression in the STAMPEDE trial in both arms.

If you look at the supplementary material, you will see that
8% of the progressions in the s.o.c. arm were new distant metastases (63 out of 758 patients progressing), while this rate was 12% in the RT arm (85 out of 685 patients progressing).
This observation does not show any trend in favor of less new metastases appearing in patients with RT, so the theory that RT to the primary leads to less new metastatic seeds can at least not be supported by this data. Bear in mind that the numbers are small.
Stampede did not include routine imaging while the patients were still not progressing, so we won't be able to see any abscopal effects (at the macroscopic level).

 

[Palex80]

You could be right but you are making a few assumptions. Even the most pro-surgery papers consistently show that biochemical failure or need for secondary treatment is higher for patients treated with upfront surgery. This is usually buried and you have to dig for the data, but it is there. This somewhat undermines the argument that at least with surgery we have a salvage option. Thats good to know because they are also more likely to need it. While guys with a local failure after RT end up in a world of hurt and you probably are helping some of them with upfront surgery, we also know they are a minority of patients and we can say with near 100% confidence that post-op RT greatly increases the incidence of long-term symptomatic toxicity compared to either modality alone. I can see where you are coming from but I am concerned this logic is setting a lot of men up for multimodality treatment and there is a real chance the balance of people helped vs people hurt may not be favorable as you think.

All that being said, its still fair to say we dont' know which, if either, is the better treatment. Its a very personal choice with pro's and con's to each. Everyone, even physicians, are entailed to their own opinions as long as they are not dependent upon exceptionally flawed data or based on demonstrably false claims.

A very good paper on exactly this issue in my humble option. In an ideal world it should be shown to any patient presenting with locally confined but agressive disease...

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy.

Carried out in Johns Hopkins, so probably not the ... worst urologists.
Less than 5% chance to remain free of biochemical progression at 10 years after primary surgery for pT3b or GS8 or pN1...

Imagine a urologist telling all his biopsy proven GS8 - patients that surgery will lead to a 5% chance of them staying recurrence free at 10 years...

 

[nkmiami]

Regarding abscopal effect- certainly possible that radiation may just lead to slower distant disease progression. In the 2 provenge trials, no difference in PSA or radiological response, but there was in overall survival, and the agent was approved.

 

[evilbooyaa]

Good discussion points. I don't think it's black and white FWIW.

I get that salvage after definitive RT is difficult. However, in the metastatic setting, are we really going to do prostatectomies, and then in 95% of patients who develop bPFS (good find Palex), radiate the fossa? I think not.

What I always remember is that surgery + salvage RT as necessary rates of bPFS are generally equal to RT alone rates of bPFS, which is why I don't feel that young patients are better served by getting surgery. Local salvage after fossa RT is a pain too.

 

[Haybrant]

Good discussion points. I don't think it's black and white FWIW.

I get that salvage after definitive RT is difficult. However, in the metastatic setting, are we really going to do prostatectomies, and then in 95% of patients who develop bPFS (good find Palex), radiate the fossa? I think not.

What I always remember is that surgery + salvage RT as necessary rates of bPFS are generally equal to RT alone rates of bPFS, which is why I don't feel that young patients are better served by getting surgery. Local salvage after fossa RT is a pain too.

I’m not sure why anyone is evening mentioning abscopal. These guys are all on systemics. Like if you brought up at abscopal at tumor board in this setting i feel that is going to make you look pretty bad. Am I wrong, maybe I don’t understand abscopal well

Second, these are metastatic patients right and they were treated as metastatic patients, meaning long term adt and systemics etc. the need to radiate the bed for BFS is not this patient group like it is a group of patients with high risk local dz that are not of any systemics bc of who knows what ridiculous reasons surgeons don’t use adt in those settings.

 

[nkmiami]

I’m not sure why anyone is evening mentioning abscopal. These guys are all on systemics. Like if you brought up at abscopal at tumor board in this setting i feel that is going to make you look pretty bad. Am I wrong, maybe I don’t understand abscopal well

Second, these are metastatic patients right and they were treated as metastatic patients, meaning long term adt and systemics etc. the need to radiate the bed for BFS is not this patient group like it is a group of patients with high risk local dz that are not of any systemics bc of who knows what ridiculous reasons surgeons don’t use adt in those settings.

That type of rational was good enough for provenge approval by the fda. No radiological or psa difference, just os.

 

[medgator]

That type of rational was good enough for provenge approval by the fda. No radiological or psa difference, just os.

Doesn't mean anyone actually used it in clinical practice, but the point still stands. Hard thing to convince patients to do without some kind of surrogate to monitor

 

[nkmiami]

Doesn't mean anyone actually used it in clinical practice, but the point still stands. Hard thing to convince patients to do without some kind of surrogate to monitor

thats always been the issue with provenge, but like radiation it is relatively non-toxic, so why not get it if you are a pt?

 

[Palex80]

I’m not sure why anyone is evening mentioning abscopal. These guys are all on systemics. Like if you brought up at abscopal at tumor board in this setting i feel that is going to make you look pretty bad. Am I wrong, maybe I don’t understand abscopal well

Well, look:

Abscopal effect is defined as the remission of a non-irradiated tumor site, due to the irradiation of another tumor site.
So you treat one bone lesion and another one become sclerotic. The effect is believed to happen by antigen release due to damage to the irradiated cells, allowing the immune system to recognize and attack the cancer cells at the other non-irradiated sites too. Also changes in the micro-milieu within the irradiated lesion seem to enhance the immune response on site.

Originally this effect was seen without the use of systemic therapy.

However in recent years abscopal was seen in patients with systemic therapy, especially with immunotherapy. Now, how does one separate between abscopal effect and effect of systemic therapy? In many of the reported cases remission happened in the non-irradiated sites during systemic therapy while disease was actually progressing. Which means that a patient went on immunotherapy, showed progression at some point, then one metastatic site was irradiated and a until-that-point progressive lesion (which was not irradiated) suddenly showed response too.

So the idea is that in stampede two things happened:
1. Less metastatic seeding due to treating the primary, killing of stem cells and potentially more malignant, higher-gleason subpopulations, which never then had the chance to spread.
2. Abscopal effect by triggering the immune system to look into the irradiated prostate, recognize malignant cells and attack them at metastatic sites.

 

[Haybrant]

Anyone have a resource that shows the dose constraints for prostate 275 x 20 like they did in this study or other hypofrac prostate constraints (not SBRT). Thank you!

 

[Sheldor]

Anyone have a resource that shows the dose constraints for prostate 275 x 20 like they did in this study or other hypofrac prostate constraints (not SBRT). Thank you!

I've been using this:

http://ascopubs.org/doi/pdf/10.1200/JCO.18.01097

Summarizes a lot of the constraints from other trials. If someone had the specific Stampede constraints though, that could be helpful!

 

[evilbooyaa]

This is from the CHhiP protocol supplement:

 

[dieABRdie]

I was going to start a new thread but found this previously posted....

Just curious... have people been able to get this approved? I have a patient with GS8 primary and one single sacral met.

Evicore is reviewing... so I know there's no way it will be approved. But was curious as to other's experiences....