In the first randomized trial of SABR (or SBRT) to the metastases of men who had 3 or fewer metastases detected via bone scan/CT, progression was delayed. This was primarily just a delay in PSA progression in the short-term (6 months) of follow-up, but there is a suggestion that the benefit may be maintained. A potential abscopal response was observed. There only seemed to be a benefit when all mets discovered on a PSMA PET scan were treated.
SABR to oligometastases slows progres... - Advanced Prostate...
SABR to oligometastases slows progression via immune response
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Tall_Allen
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This would not apply to one that has 5 or fewer metasisis and lymph node involvement also.
No. They included lymph node mets in the count of 3 or fewer mets. ( I originally wrote 5, but 3 is correct)
Got it...thanks for the info!
Great news tall Allen! Thank you. Dr. Scholls and his group have been recommending SBRT for a while now. As usual they are ahead of the curve. Interestingly, the guy I used, Told me he has a few guys that have come back and number of times to Zap new mets. It’s a bit like playing Whack a mole, But he says they seem to do well. Clearly getting the best imaging is critical given the all or nothing apparent results. Where are you at the recommending these days to get the best imaging on the west coast if you are able to pay out of pocket?
Schwah
You can get the Ga-68-PSMA-11 PET at UCLA for around $2700. Stanford is still offering the DCFPyL PET
They only treated synchronous mets (up to 3, all at once) - not metachronous (whack-a-mole). In fact, it was considered a treatment failure if any new mets popped up.
Do you believe the Stanford imaging is now substantially better than what’s being done at UCLA?
Yes. And it's free.
Thanks for the great news.
I think that the RT of metastasis did as much improvement to my condition as initial ADT + chemo. The only thing I wish could have gottent PSMA scan done before starting the second chemo. I could radiate those sites if anything is left. I wonder, if it is not too late to get PSMA scan if I had just one chemo.
• in reply tohenukit
I wonder too if it's to late for me to get a psma scan. My psa has been undetectable for for the last 9 months, so I wonder if a psma scan would show anything? I had the cancer that bone and pet scan showed, that being the pelvic bone met and the prostate/sv's. They did not radiate the lymph node...
• in reply to
"had the cancer radiated that the bone and pet scan showed"
Thanks for posting this. Good news!
I chose EBRT over SBRT, however. In this manner I and my RO feel we might not have to hit the same general area in 3 or so years when the next PET/CT shows additional mets. We shall see. I am due for the next PET in 2 weeks and will update my profile.
SBRT provides better local control:
pcnrv.blogspot.com/2019/08/...
Tests in mice suggest a moderate SBRT dose maximizes the abscopal effect:
You are beginning to see the light Allen!
This is also a commentary by Dr. Phillips from Johns Hopkins, discussing the results, and shortcomings:
practiceupdate.com/C/89651/...
I just read up on the design of the Phase II that you hyper-linked:
ncbi.nlm.nih.gov/pmc/articl...
I agree with two shortcomings: sample size, and 6month PSA primary endpoint. The authors disclosed their type2 (85%) and type1(5%) errors which is commendable.
Looking forward to the bigger RCT results. In the mean time, "oligo" patients should be doubly encouraged to discuss these results with their MOs/ROs.
I have always seen the light. In fact, I have always recommended it to patients. I think you perhaps mistook my hesitancy to recommend forgoing or delaying systemic therapy - Until there is more data, I wouldn't do that. This is in contrast to those who see oligometastatic treatment as a way of delaying systemic therapy.
TA,
If I understood you correctly,you say delaying ADT and going after treating oligometastatic is not a good idea? I have a rising PSA (.6)and I am trying to find where the cancer is to treat it and not starting ADT now. Please comment thanks.
Salvage ADT is not SOC unless there are detectable mets, rapid PSADT, or high PSA.
Thanks TA.
2 months ago, Dr. Zelefesky told me he will not recommend starting ADT at this time and he will not treat a suspicious 4 mm met on pelvic bone that did not show up on a psma scan done at NIH but showed UP as suspicious on an MRI
He said , repeat MRI in 6 months.
Makes sense - low PSA, low PSADT, no known mets
Just replace Officer Krupke's name with Doctor Zelefesky's name...
He didn't smile when I did it......
youtube.com/watch?v=j7TT4jn...
Good Luck, Good Health and Good Health.
j-o-h-n Wednesday 09/18/2019 1:40 PM DST
I guess me, Tango65, and George71 are the Jets...
youtube.com/watch?v=c9z33la...
When you're a Jet, you stay a Jet....
Don Pescado
• in reply toNPfisherman
Then there's the NY Mets. A name we've grown to fear?
It was in jest Allen -
No....George71, tango65, and I saw the light....
youtube.com/watch?v=xtolv9k...
Since you have been here....you know the truth...
Don Pescado
An important finding of this study:
"Patients randomized to the SABR arm (n=36) received radiation to all lesions detected by conventional imaging. However, they also underwent PSMA PET scans prior to and 180 days after treatment. The results of those scans were not made available to the physicians developing their treatment plans; they were used only for further analysis and comparison of cancer growth.
What they showed, said Dr. Phillips, was that patients with no additional untreated lesions detected by the PSMA PET scan at baseline (a state referred to as total consolidation) were significantly less likely to develop new metastatic lesions at six months (16% vs. 63%, p=0.006) than those whose PSMA PET scan showed at least one additional lesion at baseline (a state referred to as subtotal consolidation). Patients with total consolidation of lesions also had significantly better (4.8 times greater) progression-free survival than patients whose PSMA PET scans showed additional lesions.
What this suggests, said Dr. Tran, is that the high-dose radiation treatments are not just destroying the tumors targeted by SABR, but they are changing the course of metastatic disease.
Importantly, patients with subtotal consolidation had more new lesions,” he said. “It isn’t just that the untreated lesions are continuing to grow. This phenomenon suggests that treating macroscopic metastatic disease alters the natural history of the disease; that existing macroscopic metastases can influence the non-visible or microscopic disease development into new visible metastases.”
astro.org/News-and-Publicat...
This other study done in patients diagnosed oligometastatic using Ga 68 PSMA PET/CT and with all metastases treated, was severely criticized in this forum::
ascopubs.org/doi/abs/10.120...
Some of the comments by TA:
" By ablating the metastases with more hormone-resistant clones, one is left with only micrometastases that do not put out as much PSA. There is no "reversion." The cancer responds to ADT just as it always did, but it wasn't apparent, because hormone-resistance was judged by rising PSA.
In short, all the authors accomplished is "treating PSA" rather than treating the underlying cancer (which would require systemic therapy). They would have to look at the effect on survival to reach a conclusion that it was beneficial."
healthunlocked.com/advanced...
In summary: it seems that they were not treating only the PSA after all.
I was reading in an article recently about the (new?) theories of colonization (metastasis). Metastasis sites are not static, isolated locations. They proposed that there are "cross seeding" between colonies, which tends to preserve and enhance mutation load at each side, and make them more resistant to treatments. It does not surprise me that by reducing the number of these sites as is done here , PCa cells would become "weaker". (I'm looking for the article and can post when I find it).
Yes, there is certainly met-to-met spread. The open question is about mets one can't see. Hopefully, the immune enhancement can delay that.
Very interesting. I read something similar. I hope you will find the article.
The activation of T cells by SBRT treatment of metastases does not mean that there is an effective attack on the cancer by the immune system.. There are vaccines like Prostvac which activates T cells and generates antibodies against PSA producing cells that failed to treat castration resistant cancer.
Best of luck
I agree. T cell activation is a necessary but not a sufficient condition for an immune response. I am troubled by the small trial at COH where Provenge did not significantly lengthen PFS among those getting SBRT to a single metastasis.
sciencedirect.com/science/a...
Still, the T-cell response observed in ORIOLE is a positive finding. The question remains, is survival lengthened at all by such treatment? I certainly hope so.
Once again, you, me, and George71 were on the right side of this issue
Don Pescado
Good to know I was on the right side. But we'll have to see if survival increases. The CORE RCT has finished recruiting.
Do you know how many times you told me, George71, and tango65 that you did not believe this worked or only in localized disease?? You even said you talked to Dr Tran and he agreed with you.
Don Pescado
You misunderstood. I said, I didn't know if it worked, which is an entirely different thing. I still don't know if there is any net survival benefit. The fact that metastasis-free survival lengthened among men who had all mets treated in this small study is encouraging, as is the observed T-cell response. I don't think anyone should delay SOC ADT based just on this. Dr Tran agreed that better evidence was needed. This small study was a step in the right direction.
I wanted to add my opinion that the two most important findings here were (1) there is an abscopal effect of SBRT treatment (this was suspected from early lab studies).and (2) radiographic and not just PSA progression-free survival was delayed in those men in whom all discernable (by PSMA PET) mets were treated. It is trivial to treat PSA. Whether this will eventually translate into a survival increase won't be known for a long time. Meanwhile, if it is safe to do so, why not?
The never ending battle of getting insurance companies to pay for these scans and radiation treatments will limit how many patients can take advantage of them..My RO zapped a single met on T-10 of my spine 2.5 years ago and wrote it up as pain control to get insurance coverage..I have lots of bone mets now but T-10 is still clean !
In my experience, MOs are usually savvy about getting insurance coverage for this. If not, I hope they will read your post 
RO's get SBRT, not MO's... my MO was not involved...
Don Pescado
MOs order scans of metastases.
Is SBRT a scan of metastases? No !!! The RO orders scans prior to getting SBRT--Just FYI
Don Pescado
PSMA PET is a scan of metastases, so is bone scan/CT. In this study all men had detected mets discovered by those. The bone scan/CT was required for study entrance. Usually ordered by an MO.
I guess you think that is why MO's are so savvy at getting insurances to pay for SBRT... They don't...
Don Pescado
My RO’s response to this study TA:
I am well aware of this study. Keep in mind nobody was on hormones with the radiation (and the study was small). So the question remains does radiation add to the standard of care (which is hormones). Nobody knows...
I think that is an important point ... or both: hormones systemically and SBRT to mets. With their very short f/u (6 months) in this trial, and the endpoint which was mostly PSA-PFS, salvage ADT was not an issue. But we cannot ignore the possibility that adjuvant ADT (given with the SBRT) might extend survival (which was not proved by this trial). Some investigators believe that SBRT to mets allows a patient to defer salvage ADT. I think that is a potentially dangerous presumption, until there is more testing.
If I recall, this is basically the management strategy championed (loudly) by Gert de Meerleer at ASCO GU.
He puts his guys on a combination of ADT and SBRT for Oligometastatic recurrence, treating all sites, and letting the system therapy do the rhoomba vacuuming through the system.
There have been a good handful of retrospective studies over the past two years that are drawing the conclusion that Oligo M1 recurrence treated with SBRT and ADT is kind of like nodal recurrence treated with salvage EBRT and long-term 18-36 month ADT - a bunch of guys don’t recur by study end date of 3-4 years once re-whacked, about a quarter of them come back with polymets and a quarter of them need additional radio.
I agree that SBRT on its own doesn’t seem to be enough. Even a paper co-authored by Eugene Kwon that came out this year uttered a phrase like “putting into question the Oligometastatic state...” where the Mayo control strategy was whack a mole without systemic therapy, and 80% of the guys relapsed with new mets at 2 years, which isn’t great.
Some of the work being done at Hopkins by the ORIOLE trial guys seems to be a little more advanced in their use of combining interventions, and they’re getting better outcomes.
The most interesting curiosity for me has been the presumption that de novo metastatic guys always do worse than oligo recurrent, looking at the SEER data and a bunch of retrospective studies.
It was a pleasant surprise to see on multivariate analysis for the Hopkins paper the find that newly diagnosed guys treated curatively actually fared better than recurrent guys - that 80% progression free survival at 3 plus years with return of testosterone while hormone sensitive is a really really great number.
If I were to wonder what’s different about these guys, I’d say up until a few years ago it was bananas to treat the primary and secondaries ablatively in a metastatic setting and oncs weren’t stratifying treatments based on high volume vs low volume. Even for oligo guys 5 years ago it was just a chemical dance - Adt, Enza, abi... this new cohort however got the kitchen sink, primary secondaries and systemic.
Now if you think about that data and look at the Progression Free Survival data for SBRT + systemic for oligo recurrent guys (3 years no new mets median), you’re potentially buying 7 years without second line treatment. That’s a good number.
And then you look at the data from TITAN this year where Apa + ADT got metastatic guys like 4 years pfs median not reached, I think the space is changing and Radio guys are talking to the MOs a little more frequently, and I would bet (because anyone really who chases down Oligometastatic theory in practice has to have a gambler’s mentality), that 10 year survival rate for low volume metastatic guys treated multi modally is going to rise significantly once all the data matures.
Now with the data from Oriole you’ve got the immuno guys’ attention and you can bet you’ll see a bunch of SBRT + checkmate (ipi + nivo) trials pop up like mushrooms in the next year.
To Note: Some of this radio data also identified duration of ADT as a significant factor for progression free survival - the longer the better (but too long is a thing too!).
It’s amazing since my diagnosis last spring how much this landscape has changed, how quickly things are moving!
There actually have been no studies prior to this that found a benefit compared to what would have happened. Even here, the "benefit" was limited to reduced PSA only. The most interesting part of this study was the finding of T-cell activation, which may, down the line, delay actual progression (and not just PSA progression). There were only 6 months of f/u.
Agreed! Hit it with everything early. Very interestingly the study design criteria used the “C” word. Cure.
I am interested in this line of treatment I have just the one bone met in pelvic area but having had radiation after my prostatectomy I’m unsure if this is feasible without a prostate and of the further complications caused by another bout of radiation my consultant seems indifferent to this line of treatment but happy to refer me on to another chosen consultant in UK who specialises in this treatment
Been there, done that. I had a prostatectomy and the eight weeks of radiation to the prostate bed. The recurrence, then SBRT to a met in the hip along with ADT.
The SBRT is focused just on the single met. Three to five zaps and you're done. I would suggest a sensitive and specific scan (PSMA PET or similar) if you have not already done so just to confirm the met(s) and then go to a center where they have experience with SBRT and do it.
Yes, a pelvic bone met should be a safe place to shoot. Talk to a radiation oncologist.
Thanks for the advice I have been pondering on this for some time, it’s not yet approved as a line of treatment in UK so I will have to fund treatment myself. While all is stable at present on Zytiga Zolodex and prednisone, I feel any thing that prolongs my time before chemotherapy is worthwhile and this recent update seems to prove there are other advantages.
I had my last PSMA in Feb 2018 when the met was hi lighted and recent cat scan and bone scan this year does not identify any additional Mets
Unfortunately, they are no longer recruiting for the clinical trial at Royal Marsden. If you can get treated on the other side of the channel, there is an ongoing randomized trial in France:
clinicaltrials.gov/ct2/show...
If you just had the single met, chemo probably won't provide the benefit you need (although I disagree in general with your attitude about chemo). With a single met, radiation of your prostate and the met is probably a good idea.
That’s great! So the sbrt I had to two bone mets imaged by PSMA ctpet may have been effective after all!
Who's on first... Abbot and Costello--they at least had a sense of humor.... and could recognize a jest..
youtube.com/watch?v=kTcRRaX...
Don Pescado
Tall_Allen thanks for sharing. Are you aware, are there any studies similar to this one that the population of men have been on hormone therapy or chemo? I'm hoping to present a case to my dad's oncologist for targeted radiated but since the men in this study have all had radiation/surgery and my dad has had chemo/hormone therapy, I'm afraid that he'll reject the suggestion!
I doubt there is any benefit if the prostate has not been treated, since the prostate is the main source of oligometastases. There is a survival benefit to prostate treatment in such cases:
pcnrv.blogspot.com/2018/09/...
And while they do that, they can also treat the entire pelvic LN field.
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