Anyone considering zapping their metastases, especially at the Mayo Clinic, should read this:
Targeting Bone Metastases with Radiat... - Advanced Prostate...
Targeting Bone Metastases with Radiation in Oligorecurrent Men has No Survival Benefit in Mayo Study
Written by
Tall_Allen
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62 Replies
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Thanks for your research...have a better understanding of radiation treatments...thankfully so far no reason to consider and was hesitant to use anyway with potential side effects!
That is logical.
But it is also logical to use radiation if you have a growth impinging on something important, like say your spinal cord.
Literally got back from being treated at Mayo this afternoon. Zapped two mets on my spine which would have intruded into my spinal cord if left.
I was not looking for extended survival but staving off future complications. Feel I did the right thing.
Each case has to be looked at with due consideration. I still have other bone mets, but Mayo will not zap those with radiation.
Makes sense to me. And I don't think it is inconsistent with what Tall_Allen is saying.
The purpose was not to attempt to treat or cure.
I agree. There are palliative and preventative reasons to zap bone metastases.
Thanks, TA for posting this. The mental trauma that I put myself into trying to find the oligometastatic disease was unbearable for me. If I had to do it ALLOVER again, I would have started ADT sooner. No more chasing small cancer cells to zap while others still growing and can’t be seen.
Please excuse my ignorance, but exactly what is Oligo recurrent prostate cancer, and how it is different?
It means a recurrence of the cancer after primary therapy (prostatectomy or radiation) with metastases detected in only a few (1-5) places.
Thanks. My husband fits into this category. He has had SBRT twice. The first time was after his post Chemo scans showed some remaining mets (iliac, lymph node, prostate). Then, a year after all initial treatments, a new met was on his rib/spine at T-11. Had 3 sessions of SBRT. So, what I'm understanding is that we are wasting time and money with the radiation, correct?
As long as he is on systemic therapy, if he wants to get metastases zapped and they are in safe places, there should be no problem. This study showed there was no oncological benefit to zapping bone metastases, but it was not a definitive randomized clinical trial.
One way I like to look at it is IF my future metastases take as long to develop as my zapped metastases than maybe I’ve set back the clock a bit. Of course that’s a big IF.
There was a trial on whether the clock is set back. Unfortunately, it was a small study with some serious flaws, so there is still no light:prostatecancer.news/2017/12...
Does Mayo use PSMA for detecting oligorecurrent mets?
They use C-11 Choline PET/CT
Then they could be far from oligorecurrent in another study using PSMA?
It would probably make little difference. The median PSA at the time of MDT was 2.0. At that PSA, C-11 Choline and PSMA are about equal in their ability to detect metastases (80+%).
I had targeted SBRT. I sent this info to Dr MarkScholz and For what it’s worth his reply was :
“Better studies do show that it works”.
Like as lot of things PC , it appears to be unclear at this point.
What studies? There have been 3 very small RCTs so far, all seriously flawed. We await the results of the CORE RCT in a few years.
Good question. I’ll ask next time I see him. Either way, Seems like at best the jury is still out with nothing definitive yet. But that study showing the people with more mets and no SBRT, living as long as those with one met getting SBRT, is not real promising.
Schwah
I agree with all of that.
in reply to Tall_Allen
There is a study at Sunnybrook and a few other Canadian institutions, PR 20- will this not show a benefit ?
Tall_Allen in reply to
There are several active randomized clinical trials on MDT of oligometastases. The main ones are listed in the last paragraph of this article:
prostatecancer.news/2020/07...
As you see, STEREO (France) and FORCE (UMich) hope to have first results by 2022. CORE (UK) is expected in 2024. The Canadian ones, PCX-IX and PLATON, plan to have first results in 2025. I have no idea what they will show.
in reply to Tall_Allen
Thanks for your research - I guess tell the future is not among your tiredness contribution to this forum 😆😜
Tall_Allen in reply to
My crystal ball is in the shop 
I don't suppose that he volunteered links to those studies?? Seems to me caring, GOOD Docs would be more than happy, and sufficiently organized, to send patients info like that...otherwise, just the ole " trust me" !!
Well, there have been only 3 small randomized trials on this topic, so he is probably referring to one of them. All were fatally flawed in some way, but they were only tiny pilot studies - nothing worth changing practice over:prostatecancer.news/2019/04...
Good post and article, with a reminder to all not to dismiss the first paragraph of TA's write-up! This is NOT about using SBRT to gain "local control" (great phrase) over individual tumors, but about overall survival benefit using radiation as some localized magic bullet that has the added benefit of some positive systemic effect on PCa.
The Cleveland Clinic began a study on treating "oligometastatic" PCa in late 2019 that has since been suspended, possibly because of the pandemic:
consultqd.clevelandclinic.o...
- Joe M.
That Cleveland Clinic study is a little different. It's for newly diagnosed men who still have their prostates (while this Mayo study was post-prostatectomy or post-primary RT). They are treating the prostate and any discovered metastases. That is similar to the STAMPEDE trial that found a benefit in irradiating the prostate in newly diagnosed metastatic men.
Very scholarly analysis and you certainly have identified some lacking facts in being able to support premises arriving at the conclusion. In my personal opinion the 2014 Kwon video is not at all misleading but revolutionary. My interpretation is this -- our approach for treatment of PCa after primary treatment failure requires further thought and in cases of metastasis patients have been traditionally offered only palliative treatment options. We need to treat PCa just as aggressively as we treat breast cancer. With every weapon available. Kwon says in the video that cancer patients experience peaks and valleys in their disease progression and it is in the valleys that we need to take advantage of every possible treatment option available to provide chance at prolonging length and quality of life. I don't think anyone in this forum would disagree.
That video is certainly misleading. I think that this study with his name attached has him eating crow. It dispels all the claims made in his own video.
I listened to his videos many times. Kwon Himself admits and I quote “ sometimes we fail miserably”. So it’s not a clean cut that zapping Mets will halt progression. PC patients including me forget sometimes that cancer cells ALL over the body, seen or unseen.
At the end, he does add a disclaimer that it's just his opinion, but imo it's too little too late. He already spent almost an hour showing "gee whiz" pics of local control to get his audience excited. Unconscionable, imo. I always found it strange that Mayo never did an RCT -- being its biggest cheerleader, one would think they would be happy to have actual proof. After the publication of this study, I doubt that they ever will.
I think also it’s a timing issue. Kwon, I think is the dr who discovered the c11 col. scan, so it sounded to me at least that he is promoting the scan. No one, I think, these days will get that scan while the psma is available and has better detection rate at the lower levels of psa which he was referring to.
Mayo invested a lot in C-11 choline. They built a whole cyclotron and manufacturing facility. I'm sure it cost tens of millions of dollars. They will not give up on it that quickly. Even Axumin is more sensitive at lower PSA than C-11 Choline, and they never offered Axumin to their patients.
Same reason for slow adaption of LU-177 and AC-225 ?
There can be no adoption of either drug in the US outside of clinical trials until the VISION clinical trial is completed and results compiled, and the drugs are FDA approved. It will be the first time anywhere in the world that we will know whether and by how much those drugs improve survival.
The PSMA pet scan should be offered so those looking to go abroad for treatment have a way to know beginning amount of cancer and results after treatment. Also to know what there uptake results. Still as it is approved FDA now only a few places offer it even though they have the ability to provide the test.
Axumin is not more sensitive than Choline C-11 in soft tissue. Axumin works best for bone mets. I paid OOP $10K for 2.
Yikes - that's expensive! Was it worth it?
There was a direct comparison at the University of Bologna. They found:
"On a patient-based analysis, 18F-fluciclovine detection turned out to be significantly superior to 11C-choline (P < 0.000001). This result was also true on lesion, lymph node, bone lesion, and local relapse analysis (P < 0.0001 in all the cases). There was no significant difference in terms of target to background of positive lesions between 11C-choline and 18F-fluciclovine. When the patients were divided into groups with different PSA levels, 18F-fluciclovine had a superior detection rate for low, intermediate, and high PSA levels."
journals.lww.com/nuclearmed...
Do you have different studies?
Thanks for posting this TÁ. What is your knowledge on using oligo SBRT/MDT to lower the cancer burden on patients being on ADT. Could this/will this prolong the effect of the ADT and the median time until castration-resistance?
There is a logical problem in some oligo studies - it is called "treating PSA." It is discussed in this article:prostatecancer.news/2020/07...
Answer this question - By what biochemical mechanism can spot treatment of a few metastases change the phenotype of the cancer to make it more hormone sensitive?
Thank you for a fast reply. Really appreciate it.I’m not in the belief that spot treatment can change the phenotype of the cancer and make it more hormone sensitive. I was simply wondering if lovering the overall cancer burden would/could prolong the effect of ADT. Let’s say a person with low but rising PSA has a PSMA PET that shows Oligo metastasis. Will/Could SBRT/MDT of the few visible mets make the ADT added after the radiation treatment last longer? Logic is micro metastasis take longer to grow and become resistant. It this the case to your knowledge?
Systemic therapy certainly lowers the cancer burden, and prolongs the time to castration resistance. Irradiation of the prostate, which is the source of all metastases, has that effect if it is done early enough. But destroying the motherlode is a far cry from zapping the few tumors that one can see.
The only way one can know if zapping tumors has that effect is if radiographic recurrence is delayed by it (biochemical recurrence is useless because one has "treated PSA"). The Mayo study says no, at least not if there were any bone metastases. As you read, there are serious problems with the LN part of the study. In a few years we will have larger randomized trial results.
I wanted to add that increasing time to castration resistance is not a benefit if prostate cancer survival is not thereby extended. Systemic therapies- Chemo, Zytiga, Xtandi and Erleada do both in the newly diagnosed. Maybe in recurrent men as well.
Hello Tall_Allen, the somatic mutations of the clonal populations in a a given metastasis may vary from other metastases (although there is exchange between metastatic sites) . I believe I have read papers where MDT has resulted in the killing of ADT resistant clones in a metastasis and a (temporary) return to control with ADT. Cheers, Phil
How would they know? When you spot treat, you are destroying the source of most PSA, so PSA goes down. It appears that the patient is again hormone sensitive (we judge castration resistance by increased PSA or increased size and number of metastases), but are we only masking it? That's why it's not a useful endpoint. Bottom line is if there is no increase in prostate cancer-specific survival as a result of MDT, it was for nought (except for palliative purposes).
I assumed that if a patient has one or more metastatic sites then surely he has other metastatic sites which cannot be imaged or are dormant. If one or more metastases are ablated and the PSA drops and remains low/stable then control is temporarily re-established until other sites become resistant. I agree that PSA does not provide a complete picture. Cheers, Phil
That is called "treating PSA." We have to treat the cancer, not PSA.prostatecancer.news/2020/07...
Mayo does offer some strange non-evidence based options on a case by case basis. For example I was stage 4 and 43 years old when I was initially diagnosed but I still was offered an RP and did it. Knowing what I know now I would never have done it again. I also elected to treat a bone met in T1 for fear of compression and paralysis so I did 3 treatments with local radiation. It worked but of course you can’t account for all the micro metastatic disease not seen on imaging. And...as the article and TA discussed this does not improved survival. I remember that first year and how “we” (the Mayo team) were going for cure. I believe in hope but I don’t think this was a fair treatment plan for someone with stage 4 disease.
My impression is that Mayo (like Johns Hopkins) has very strong urology/surgery and basic research departments but a very weak radiation oncology department. Unlike Johns Hopkins, they are light in urologic oncology expertise as well. I've found that many surgeons have a "hot dog" mentality - they think they can cure anything with a scalpel. I agree that part of a doctor's role is to manage expectations. He shouldn't be making promises he can't keep, but neither should he be fostering doom and gloom.
Thanks for the excellent info again from you.I am a Mayo Phoenix patient.
My MO is not a believer of zapping.
He will only use it for pain.
Just start Zytiga 30 days ago - PSA went up. How long does it usually take to begin working?
Thanks
Tall_Allen in reply to
An early PSA flare occurs with many new therapies because of cancer cells dying, which is a good thing. Most guys who see a favorable response, see it within the first 2 months.
in reply to Tall_Allen
Thanks TA
I quote from the full article (description and opinions are from the authors of the study):
"Our results confirmed that MDT (metastasis directed therapy) was associated with
better oncologic outcomes than ADT in patients with PCa
(prostate cancer)
nodal recurrence. sLND (salvage lymph node dissection) had better 5-yr CSM (cancer specific mortality) free rate than
ADT (93% vs. 80%; p < 0.01).
Moreover, MDT was associated with longer RAR (radiological recurrence), CRPCa (castration resistant cancer), and SST(second line systemic therapies)
free survival than ADT.
Our findings are in line with those from Davos
et al. [20] since we showed a 5-yr CRPC-free survival of
77.4% and a median SST-free survival of 78 months for the
MDT group, thus contributing to the increasing amount of
evidence supporting the role of active treatment in this
setting.
When each MDT treatments were considered individually, we found that both sLND and EBRT (external bean radiotherapy) were associated with better outcomes, as compared to ADT. However, survival outcomes were similar for sLND vs.
EBRT. We found that MDT was not associated with survival benefit as compared to ADT in patients with bone
metastases.
Our results are in line with data for primary N1
PCa, for which maximizing locoregional control with RT
(radiotherapy)
improves survival as compared with ADT alone [21].
The importance of our study in relation to previous
reports consists of several aspects.
This study contributes to
the growing body of literature suggesting a potential
advantage of metastasis-directed therapies to the lymph
nodes over ADT in oligometastatic patients [5, 6, 10].
Several differences from previous studies should be noted:
as compared with the study from Ost et al. [6], we assessed
the oncologic benefit of MDT separating patients with
node-only recurrence from those with bone oligometastatic
disease. In fact, it is well known that patients with PCa
nodal metastases had better prognosis compared with their
counterparts with skeletal or visceral metastases [7, 8].
According to our results, MDT was associated with better
oncologic outcomes in patients with oligometastatic nodal
recurrence; whereas patients with bone metastases might
benefit more from a systemic or multimodal treatment. "
Conclusions
"sLND and EBRT were associated with better RAR (radiological recurrence), secondline systemic therapies and CRPCa (castration resistant)-free survival as compared with ADT in patients with oligometastatic PCa nodal
recurrence.
No difference in survival outcomes was observed between sLND and EBRT. MDT was not associated with survival benefit in patients with bone metastases, as compared with ADT.
Larger prospective studies with longer follow-up and
stronger oncological endpoints comparing sLND with the
current standard of care and other interventional strategies
(EBRT) are needed to provide high-level evidence."
Thank you for sharing.
Good analysis. I am struck by the median times and % to castrate resistance in all of the groups. Apparently considerably longer than the “typical” average cited of 20 to 24 months.
Thoughts?
“After a median follow-up of 47 months:
Prostate Cancer-specific mortality was 13.5% for ADT-only, 9.5% for EBRT, and 6.3% for sLND (the difference between ADT-only and sLND was statistically significant)
Radiographic recurrence was 65% for ADT-only, 40% for EBRT, and 61% for sLND.
Castration-resistance was 39% for ADT-only, 19% for EBRT, and 21% for sLND.
The median time until castration-resistance set in was 59 months for ADT-only, 73 months for EBRT, and 98 months for sLND.”
2 years to castration-resistance is only when metastases are detected by bone scan/CT, not c11 PET scan. Detection and start of therapy, whether ADT-only or MDT, was much earlier at Mayo.
Hello Tall_Allen, as usual, a very thoughtful and thorough review. I just want to add that many men with metastatic disease are typically on some form of ADT or neoadjuvant therapy and if they receive RT then the outcomes will likely be different from those obtained from the Mayo Clinic retrospective study. There are numerous studies indicating the benefits of combined ADT and RT, which appears to modulate the immune system. Cheers, Phil
You may have missed this: "All of those receiving MDT for bone metastases were also receiving ADT."
I would like to add that I had two different sessions of cryo to my spine and ribs with a great deal of success. Mayo Rochester, Dr Morris
How was it "successful"? Pain palliation?
Hello TA, I had a half dozen tumors, or more, on my spine and ribs. They froze and burned them, they went away, and so did the pain and progression. I might add that I immediately started Xtandi, was already on Lupron, and today my PSA is undetectable and scans show no activity. And Im still here to irritate my wife of 31 years
😀
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