Until recently, there has been very little data supporting non-cranial stereotactic body radiotherapy as metastasis-directed therapy. However, in 2019 the SABR-COMET study was published in The Lancet.1 This randomized, open-label Phase II study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia that randomized 99 patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus stereotactic body radiotherapy to all metastatic lesions (SABR group). Over a median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group, median overall survival was 28 months (95% confidence interval [CI] 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio [HR] 0.57, 95% CI 0.30-1.10; p=0.090). Recently published long-term outcomes of this trial showed durable findings.2 Over a median follow-up of 51 months, the 5-year overall survival (OS) rate was 17.7% in the control group (95% CI 6% to 34%) versus 42.3% in SABR group (95% CI 28% to 56%; stratified log-rank p = 0.006), and the 5-year progression-free survival (PFS) rate was not reached in the control group (3.2%; 95% CI 0% to 14% at 4 years with last patient censored) and 17.3% in the SABR group (95% CI 8% to 30%; p = 0.001):
In his opinion, there are two main strategies: (i) using metastasis directed therapy alone (to delay need to start systemic therapy), and (ii) use of metastasis directed therapy with systemic therapy.
There have been two Phase II trials assessing metastasis-directed therapy for oligometastatic prostate cancer. In the STOMP trial, Ost and colleagues randomly assigned 62 patients to either surveillance or metastasis-directed therapy of all detected lesions (surgery or stereotactic body radiotherapy), with a primary end point of androgen deprivation therapy (ADT)-free survival. At a median follow-up time of 3 years (IQR 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI 12 to 17 months) for the surveillance group and 21 months (80% CI 14 to 29 months) for the metastasis-directed therapy group (HR 0.60, 80% CI 0.40 to 0.90; log-rank p = 0.11):
The second Phase II trial published recently was the ORIOLE trial,4 randomizing 54 men in a 2:1 ratio to receive stereotactic body radiotherapy or observation. The primary endpoint for this trial was progression at 6 months, defined as a prostate-specific antigen (PSA) increase, radiographic or symptomatic progression, ADT initiation, or death. Progression at 6 months occurred in 7 of 36 patients (19%) receiving stereotactic body radiotherapy and 11 of 18 patients (61%) undergoing observation (p = 0.005). Furthermore, treatment with stereotactic body radiotherapy improved media PFS (not reached v.s 5.8 months; HR 0.30, 95% CI 0.11-0.81; p = 0.002):
Dr. Cheung concluded his presentation with the following summary remarks:
* The SABR-COMET trial gives a strong signal that stereotactic body radiotherapy can improve PFS and OS in metachronous oligometastatic prostate cancer
* Two small published randomized Phase II studies in oligometastatic hormone-sensitive prostate cancer revealed that surgery/stereotactic body radiotherapy for metachronous metastases can delay progression and the need to start ADT (if one considers surveillance to be an acceptable option to compare against)
* Starting ADT can be considered a surrogate of development of polymetastatic disease in the STOMP trial, and surgery/stereotactic body radiotherapy delayed start of ADT
* There is no randomized data evaluating the use of metastasis-directed therapy in the setting of synchronous (de novo) hormone-sensitive oligometastatic prostate cancer
* There is no randomized data evaluating the use of metastasis-directed therapy in combination with standard (or any) systemic therapy in the setting of hormone-sensitive oligometastatic prostate cancer
* Stereotactic body radiotherapy is very well tolerated for the most part and it is likely best used in combination with systemic therapy for hormone-sensitive oligometastatic prostate cancer
What is the difference between synchronous (de novo) hormone-sensitive oligometastatic prostate cancer and metachronous oligometastatic prostate cancer?
Synchronous means all at once. Metachronous means one after another.
So in the STOMP trial, in the MDT group, they zapped up to 3 synchronous metastases (median =1 met) initially (de novo), all at once. Then, they kept zapping as new ones popped up (metachronous), like playing whack-a-mole. They continued doing this until 3 new ones popped up all at the same time. At that point, they started them on ADT.
In the surveillance group, they had a median of 2 metastases initially. They started them on ADT as soon as 1 more met appeared (a total of 3 at once).
So you see, the bar was set lower for the MDT group. Even so, the time to ADT was not very different statistically (only 80% confidence).
So we are nowhere near figuring this out. In defense of all 3, they were only small Phase 2 trials that were never meant to influence practice. Better Phase 3 trials are in the works.
“Maha Hussain reported the results of a randomized clinical trial comparing intermittent vs continuous ADT in recurrent men with metastases. She found that:
Time to castration resistance was not different for the two protocols”
Does the word “time” in this context mean the total amount of time on ADT, in which case the absolute time to CR would be longer for IADT, or does it mean absolute time, in which case the IADT group had less time on ADT but reached CR in the same amount of time as the CADT group?
The latter. It means the time from when the patients were randomized to either intermittent or continuous ADT. They were randomized to one group or the other after showing they responded to ADT.
They do note that: "Men in the IADT arm who became CR while off treatment (rising PSA in the absence of any testosterone recovery) had to be restarted on treatment and have 3 further rises in PSA before declared CR." So this resulted in a 4-month delay in declaration of castration resistance in the IADT arm. After subtracting the 4-month delay in finding their CR, there was no difference. In fact, the cADT group survived 4 months longer after CR, further demonstrating that it was only an artifact of the research design.
Yes. It set out to prove that intermittent wasn't inferior to continuous in metastatic men. It could not prove that. It was inferior (by an average of about 10%) for most men, and particularly for men with few metastases (by an avaerage of 19% worse). For some men iADT was over 20% worse (which is what they had pre-decided they would call a meaningful difference), but for some men it was up to 1% better. So they realized that they would need a much larger sample size (1000 more patients).
Although the trial was statistically inconclusive, Hussain cautions: "However, given that nearly the entire confidence interval (0.99-1.23) tends to favor continuous therapy, the result suggests that intermittent therapy may compromise survival. The lack of a significant difference between the groups does not imply similar survival."
What is covered by Medicare for these patients? Here is an apparent new trial that seems to be based on the experience a Cleveland Clinic patient had....
yes, for men who first present with metastasis, without having any previous treatment. Right? I'm assuming that SOC may be to skip any surgery with this type of presentation....so doing surgery would be the trial part? Somewhere I read about another study like this...surgery was beneficial in that study..not sure how beneficial?
Two trials- STAMPEDE and HORRAD - proved that debulking the prostate with radiation had no oncological benefit unless the metastatic burden was very low. The same would probably be true with surgery.
Per the article that provided the link I posted...evidently idea for trial began with patient who was oligo, had all 3 treatments, and now " almost cancer free" at 8 years. probably another explanattion, but for some reason these docs thouth worthwhile to do a study. The article was the basis for someone's post here a few days ago..and that article included a link to the trial details I think I recall...remember my detail retention issue!! chuckle? I'll read your provided study links...later.
Yes, that's why we don't base treatments on anecdotes, although anecdotes can provide the impetus for clinical trials. Right now, there is no convincing evidence that MDT is useful. But as I always say, if safe, why not?
Dr. Cheung concluded his presentation with the following summary remarks:
* The SABR-COMET trial gives a strong signal that stereotactic body radiotherapy can improve PFS and OS in metachronous oligometastatic prostate cancer
it is the future -- it is done with every other type of cancer...
That is incorrect. There were only 2 prostate cancer patients in the control group and 14 in the treatment group. In the 2-year follow up, none of the PC patients died in either group.
You are also incorrect that it is routinely done in every other type of cancer.
"Dr. Cheung concluded his presentation with the following summary remarks:
* The SABR-COMET trial gives a strong signal that stereotactic body radiotherapy can improve PFS and OS in metachronous oligometastatic prostate cancer"
You should call or email the doctors and tell them you are a blogger on a cancer forum and although you have no medical degree in anything -- that they are incorrect .. and should listen to you ... and see what they say .
George..you raise many good questions on this forum and I am impressed with some of the information you surface. Keep it coming. But you appear so defensive when Tall Allen posits a contrary view. I intervene here because so many us are eternally grateful for TA’s presence on this Board. He is a treasure . A man who does not have to spend the time to do all he does. That has clarified so much for so many. Please be respectful. We are respectful of you. Please reciprocate to all.
No, I'm not wrong. See Table 1 in the link below of his extended f/u. I even discussed it with Dr Palma. He plans to change his methodology for his Phase 3 trial because of it.
Hey guys...can we all be a little more diplomatic maybe I know everyone here is well-intentioned......maybe " I believe you are incorrect" instead of "you are wrong"...or " i just believe you are wrong" or I believ you are misinterpreting what you have read". TA and George.....we appreciate both of you very much!!
Allen, I am a guy has been accused of being too blunt and non-diplomatic, even though of course I had not viewed my statements that way. But i'm imperfect..who would have thought that! So, probably I fail more than I believe I do. Not sure what is meant by troll...Wiki says this....
" In Internet slang, a troll is a person who starts flame wars or intentionally upsets people on the Internet by posting inflammatory and digressive,[1] extraneous, or off-topic messages in an online community (such as a newsgroup, forum, chat room, or blog) with the intent of provoking readers into displaying emotional responses[2] and normalizing tangential discussion,[3] either for the troll's amusement or a specific gain.
Both the noun and the verb forms of "troll" are associated with Internet discourse. However, the word has also been used more widely. Media attention in recent years has equated trolling with online harassment. For example, the mass media have used "troll" to mean "a person who defaces Internet tribute sites with the aim of causing grief to families".[4][5] In addition, depictions of trolling have been included in popular fictional works, such as the HBO television program The Newsroom, in which a main character encounters harassing persons online and tries to infiltrate their circles by posting negative sexual comments.[6
I'm not under the impression that there are such persons commenting on this forum..but maybe I'm blind to it? Certainly not you...or me!!
Not sure how I'm feeding the trolls? You and George were going back and forth, and I stated my appreciation for input from both of you! I think you said something like "you are wrong" in response to george's opinion on something..then he indicated unhappiness with such a direct correction...and then back and forth, which i understand as an outsider to the exchange. I don't know.....I was just trying, maybe mistakenly, to help cool the situation. Sorry if I goofed !! So, I was referring to your " you are wrong" comment...where maybe some folks have no problem with being so directly corrected, other folks are more sensitive. Face to face, I've told acquaintances that they are wrong....reflecting, maybe in future I'll try to be more diplomatic? especially with wife...chuckle?
Live, and maybe learn? I try.
I've been on both liberal and conservative comment threads, and been acused by both extremes of being a troll. No, just made a statement not in conformity with the prevailing opinions of the majority on that thread! What's the point of a site where all folks do is congratulate each other on their same views???
I took your comments to be constructive and well intended.
I agree completely ... I have said several times ... we are ALL just PCa patients here .. looking to share our experiences / treatments / progress etc.
When I or others are talked down to or belittled like T/A frequently has done to many here before– (surely you have noticed it almost always involves T/A) we respond to his offensive comments with facts..
I simply point out that when T/A says that the DOCTORS are wrong (in this instance Dr. Cheung etal) I simply pointed out that DOCTOR Chenug and his research team are DOCTORS and T/A is not – and if it comes down to who to believe I will stick with the doctor not T/A who is not a doctor of anything. …
– or when T/A said Dr. Kwon (and by extension Mayo Clinic) are INTENTIONALLY misleading his patients; or when he said that the world famous Mayo Clinic has a weak oncology dept; implying that they aren’t qualified --- (apparently like T/A is) or when he said . that Dr. Kwon is merely a urologist – I must remind him that he is not a doctor in any medical field including urology.
I know (off the top of my head) of 8 or 9 former posters on here that have left this forum and joined other groups because of T/A and his defenders talking down to them in an attempt to control the narrative. T/A responses are derogatory and disrespectful or they wouldn’t have left... his defenders come on and say you are being double teamed – and they are here to help ! Like it is a football game...LOL It clearly illustrates their mindset – rather than allow others to post new and developing treatments possibilities they insist on SOC … This isn’t a doctors office here – no on is qualified to determine anything for anyone here.
-- its just not that cut and dried – I’ve talked to 7 or 8 different doctors and have been given a differing opinion from everyone of them.
We all know what SOC care is and we all have DOCTORS or likely multiple DOCTORS...
If he thinks the doctors and Mayo Clinic are really intentionally misleading the public or their patients he should tell the DOCTORS … not try and discredit the people who merely post the DOCTORS articles and videos for others here to read and disseminate for themselves...
T/A could do like everyone else – simply say he has seen other studies that concluded the opposite or whatever and post the link with the quoted section of the article that pertains …explain his reasoning – then no one takes offense. But that way he doesn’t get to present himself as the all knowing authority above the doctors.
Thank you George..again I really can't imagine that anyone here is not well-intentioned.....different personalities for sure. I'm known for being stubborn, etc. I always say,,,,,so I'm stubborn, and you(the other person) are not? I think things may be said a certain way in forums that would not be the case if in-person face-to-face. Something to distract from my cancer fears today....roof leak...oh boy! Time to bring out the hose and see if can locate the source?
7-8 Docs and all different opinions..not good. How then can an insurer claim there is a SOC?
" That is incorrect " ........." You are also incorrect "......... " You should check your facts before commenting. " Some folks may not mind being told these things, I agree. However, other folks are more sensitive,might become defensive and fire back...thus my comment about diplomacy on both sides. That was all.
I was responding to his comments: "The SABR-COMET trial gives a strong signal that stereotactic body radiotherapy can improve PFS and OS in metachronous oligometastatic prostate cancer" and "it is done with every other type of cancer..." Both statements are factually incorrect for the reasons I stated. I don't think they are incorrect, they are factually incorrect. The first was the opinion of Dr Cheung which was incorrect because the lopsided distribution in the Phase 2 trial - Palma didn't even report results for prostate cancer separately, so how can it possibly be true. I don't know why he thought it is done for every other cancer (other than experimentally).
I agree with your characterization of the troll on this forum. This is someone who posts misleading or incorrect information and gives bad, if not dangerous advice. Thanks for continuing to correct this.
"Dr. Cheung concluded his presentation with the following summary remarks:
* The SABR-COMET trial gives a strong signal that stereotactic body radiotherapy can improve PFS and OS in metachronous oligometastatic prostate cancer"
You should call or email the doctors and tell them you are a blogger on a cancer forum and although you have no medical degree in anything -- that they are incorrect .. and should listen to you ... and see what they say .
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Advanced Prostate Cancer Bone METASTASES 
Father with prostate cancer and liver metastases 
Recommendations for metastasized prostate cancer clinical trial options?
Survival rates for prostate cancer with bone metastases
