Non SOC radiation options for metastatic - Advanced Prostate...

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Non SOC radiation options for metastatic

CantChoose profile image
47 Replies

I've noticed some of you talking about brachy or stereotatic irradiation for metastatic disease. What are these options and how are they being implemented (clinical trial, rogue doctor, etc.)? I haven't found much background info. (I'm not talking about the isotope-membrane PSMA stuff.)

Or are the people using these options all dealing with more contained disease?

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Fairwind profile image
Fairwind

Once Bone Mets are discovered, most RO's and MO's feel radiation in any form is counter-productive.. However, for treating bone pain, SBRT is approved and is frequently performed..What can happen with PC, if just one or two mets show up, the patient can complain about pain in those spots and an RO may zap them to control the pain. This "pain" may or may or may not actually exist...But it allows the RO to be reimbursed by your insurance..

NPfisherman profile image
NPfisherman in reply to Fairwind

Fairwind,

I disagree that most RO's feel that SBRT has no value after bone mets are discovered--a few articles below....especially in oligometastatic disease... while Dr Heron is finishing up Phase 2 trials at UPMC....they are now looking at benefit from treating 4-10 lesions--separate study-- ....SABR-COMET-10... I guess we shall see:

renalandurologynews.com/hom...

ncbi.nlm.nih.gov/pmc/articl...

urotoday.com/conference-hig...

astro.org/News-and-Publicat...

Fish

tango65 profile image
tango65 in reply to NPfisherman

Good references. I posted about this:

healthunlocked.com/advanced...

and the concept of treatment of oligo metastatic patients was severly criticized. I think that many people do not realize that with Ga 68 PSMA PET/CT diagnosis of mets these patients have a very early oligo metastatic situation and the direct treatment of metastases could delay the start of ADT or the new anti androgens or chemo. Once one is on ADT and/or the new anti androgen, or chemo etc, is the beginning of the road to castration resistant cancer and mutated cancer impossible to stop.

NPfisherman profile image
NPfisherman in reply to tango65

Agree....I found my one lesion with an axumin scan--not as good as PSMA but was all I was offered and even then, insurance tried to say no... I believe the PSMA offers the best option to find cancer in an "oligometastatic" state and kill tumors...I am waiting for the new scan using fibrinogen activation protein which should be useable when PSA is "undetectable"...no reliance on PSMA...a chance to track the cancer down and kill it while in an even weaker state... we shall see...

I enjoy reading your posts and replies....wish you the very best...

Take care, tango...

Fish

NPfisherman profile image
NPfisherman in reply to tango65

Went back and re-read your post....I replied to you...I believe stereotactic radiation will be part of the answer...eradicating tumors may not be curative...but decreasing tumor burden, by logic, should add to OS time... I missed where a certain poster and company....jumped on your back... apologies....I guess you, me, and George71 are believers....the Phase 3 on this should put it all to rest, and I believe we will be found to be on the right side of this argument....

Fish

tango65 profile image
tango65 in reply to NPfisherman

I agree. I believe that reduction of the tumor load may provide a better chance to the immune system to control the cancer.

CantChoose profile image
CantChoose in reply to tango65

My husband and I refer to this as the "warts cancer." A compromised immune system lets warts get out of control, and getting the immune system to wake up and attack the virus is key in warts. However, cutting them off, burning them off and covering them can help immensely in the meantime. I'm guessing that targeting these cancer cells, wherever they are, may be similar.

tango65 profile image
tango65 in reply to CantChoose

You assume the immune system attacks cancer cells the same way it could attack a virus causing warts. I remember treating my warts with liquid Nitrogen and having the problem solved for a long time.

CantChoose profile image
CantChoose in reply to tango65

I meant it more as a metaphor. With so many cancers, you don't want to disturb the primary site because it triggers rapid growth in metastases. In prostate cancer, it's far more like a wart colony or moles.

407ca profile image
407ca in reply to NPfisherman

Agree. It just stands to reason that killing off whatever cancer is known to exist should help O S. Really, otherwise why do any treatment at all.

Thanks Fish and Tango too.

NPfisherman profile image
NPfisherman in reply to 407ca

Most welcome .... Phase 2 data from Dr Heron's study indicates benefit,,,,they are looking at stereotactic radiation for recurrence post tx as well....I believe that you kill the tumor and shedding of CTC's stops... Does another met grow somewhere ??? Yes, but it is a start over and is buying..... Time..... I'll take that....

407ca profile image
407ca in reply to tango65

Bingo. You got it right, why not try it is the question? Yea, perhaps a waste of time but still why not try? It might not work is a lame response INHO.

CantChoose profile image
CantChoose in reply to 407ca

I think you have to weigh the cost of each treatment though in time, expense and risk. My husband is starting on third base with this cancer so we have less time in general for treatments.

I kind of wish we had pushed the conversation more about debulking when he had the TURP, but that's urine under the bridge. :)

407ca profile image
407ca in reply to CantChoose

Urine under the bridge? Great phrase.

All the best for you and yours.

407ca profile image
407ca in reply to tango65

Thanks for posting that Tango. My goal is to delay ADT, a cure is not in the cards. The doctors I have dealt with feel there is value in zapping the mets and retreating the prostate. I am well aware of the risks and know is might not be SOC. My choice. Some do criticize this but at some point everything is new and untried. If we keep working at the imaging and precision will improve and my bet is that it will be accepted. Time will tell.

All the best Tango

in reply to tango65

so would you think radiation therapy for oligometastatic patients (or for local advanced) should be done without ADT?

tango65 profile image
tango65 in reply to

That it is what it was offered to me (direct treatment without ADT) before they decided that it was not possible to treat all the metastases . I had 4 large lymph node metastases but there were many other suspicious lesions in the Ga 68 PSMA PET/CT. I started ADT and I went to Germany and I got treated with Lu 177 PSMA. When the metastases were gone I stopped ADT but my testosterone never recovered . No MO wanted to give me testosterone. I continued in an unplanned ADT and the cancer is becoming castration resistant. My mistake was to accept ADT treatment before the Lu 177 PSMA treatment.

NPfisherman profile image
NPfisherman in reply to tango65

Sorry to hear this information, brother....I have a friend on the forum who got radiation and Lupron.....when it was time for IADT, they refused him dutasteride and he has a recurrence...another brother stopped ADT and started dutasteride---his initial PSA was 580 and he remains "undetectable"....I believe rapid T recovery may have real value in these endings of ADT to prevent/ slow recurrence...

Fish

jdm3 profile image
jdm3 in reply to tango65

I understood ADT may be synergistic with Lu-177 increasing the efficacy by making the lesions more PSMA avid. Perhaps the ADT actually helped in that case so may not necessarily have been a mistake (??). Wishing all the best, Josh

407ca profile image
407ca in reply to NPfisherman

Fish,

Those were very good articles. Thank you for posting them.

NPfisherman profile image
NPfisherman in reply to 407ca

You are most welcome....Stereotactic Radiation is one of the areas I follow....George71, and tango65 also are followers. You as well I am thinking...In fact, like most....I try and follow everything....I am excited by the new fibrinogen activation protein scan with the hope they can attach radioisotopes to the scan medium as treatment. Should work even when PSA is "Undetectable"....That ought to slow things down and perhaps...using other methods in conjunction--- some cures. The multimodal approach... watching the science with..... HOPE....

Fish

407ca profile image
407ca in reply to NPfisherman

George has some excellent posts. I always read them.

NPfisherman profile image
NPfisherman in reply to 407ca

Me too !!!!

407ca profile image
407ca in reply to NPfisherman

Fish,

I know little of the fibrinogen activation. Can you post about it as you find out more? I am always interested in new stuff. Been at this for 13 years and although sometimes things seem to proceed at a snails pace, there have been many changes.

Best to you Fish

NPfisherman profile image
NPfisherman in reply to 407ca

Here you go, amigo.....

sciencedaily.com/releases/2...

The latter part of the article they talk of attaching radionuclides--Lu-177 or AC-225 perhaps to FAP....

All the best,

Fish

Mish80 profile image
Mish80 in reply to Fairwind

I thought that targeting Mets can help thrink them and prevent further growth..

snoraste profile image
snoraste

you should look up "multimodal" therapy on this forum. It's a hotly debated topic here. For Oligometastatic disease, a combination of ADT (possibly with Zytuga/Xtandi) and metastasis directed radiation has proven to be far superior than the drugs alone in clinical trials. There's a lot of debate here on this forum and in the clinical community about the benefit of such multimodal treatment for patients with widespread metastasis. There're a couple of clinical trials right now trying to answer that question.

CantChoose profile image
CantChoose in reply to snoraste

Thanks! That was the search term I was struggling to find. :)

Sounds like my hubby has too many mets anyway.

NPfisherman profile image
NPfisherman in reply to CantChoose

If he has 4-10 lesions, then he would qualify for SABR COMET-10 trials....it is worth looking at if this is his status IMHO.... Good luck....

Don Pescado

CantChoose profile image
CantChoose in reply to NPfisherman

Yeah, the doctor thought that was possible, but he's 20+. :(

Tall_Allen profile image
Tall_Allen

There are several different situations in which those therapies are used:

1) primary therapy (SBRT or brachy or brachy boost) for localized PC

2) salvage therapy after primary RT failure (salvage SBRT or salvage brachy) for localized PC

3) treatment of oligometastases (SBRT) after recurrence

4) debulking of the prostate after oligometastases have been discovered

There is high quality evidence for #1 (large RCTs, and multi-institutional), medium quality for #2 (small, single institution non-randomized trials), no evidence for #3 (there are clinical trials in the works), and medium quality for #4 (a subset of the STAMPEDE trial)

CantChoose profile image
CantChoose in reply to Tall_Allen

TA, from what I've read, it seems a TURP involves about half the tissue removal of a debulking. If they're in there anyway, why aren't they taking as much of the prostate as possible during those types of procedures?

Tall_Allen profile image
Tall_Allen in reply to CantChoose

Most prostate cancer is in the peripheral zone; BPH is usually in the transition zone, so the tissue is removed from a different place. Only a radical prostatectomy gets rid of it all -and the urethra has to be reconnected.

407ca profile image
407ca

Cantchoose,

I have had stereotatic radiation to 4 nodes and one bone lesion for oligometastatic disease. It was done in the USA utilizing a PSMA scan from Europe.

How this came about...I went to MD Anderson and the oncologist told me I was oligmetastatic. He told me that treating the mets was being found to be of benefit and found a radiologist at Cleveland Clinic near my home who would do it. Neither of them were rogue doctors.

Some argue that treating the mets will do no good but I disagree and I feel that with time, it will increasingly be seen as beneficial. The M DA and Cleveland Clinic doctors felt so as well.

I then went to Finland and had a Tulsa Pro treatment to the prostate when there was a known recurrence as well. This was done at a University teaching hospital, again by very well respected doctors.

Some might think it pointless but these doctors thought otherwise. I think the naysayers are behind the curve in MHO. Besides, it stands to reason, would you rather have ten tumors or one or two? No, I am not cured but my team things we beat it back , which was the goal all along.

Fish got it right.

All the best.

Tall_Allen profile image
Tall_Allen in reply to 407ca

What you believe may or may not be true - the point is that there is as yet no evidence to support it. And that is what is known at the leading edge of investigation, not "behind the curve." You are also making a common logical error in supposing that what you can see is all there is. Getting rid of ten visible tumors exposes one to radiation toxicity - if there is no survival benefit, why do it?

407ca profile image
407ca in reply to Tall_Allen

No error here. I know very well that there is more than I can see as no imaging can pick up individual cells in circulation. Still, what is better 10 lesions or 1? And yes, radiation does have toxicity as does ADT.

So do we not do ADT because of it, of course not. Same can be said of treating the mets. Also, at some point it time, SBRT , IMRT etc. were new and without "proven" results.

Not sure how one could ever design a double blind study on this.

Tall_Allen profile image
Tall_Allen in reply to 407ca

It is better to be at the point of progression where there is only one visible lesion than 10. However, if you have gotten to the point of progression where there are ten visible lesions, it may not matter if you reduce the number of visible lesions by zapping them. You believe that zapping only those mets that are visible has some benefit? That is exactly what is being tested. It is not double blind, but it is randomized.

To understand why randomization is essential, you have to understand the natural history of cancer progression. We know it takes about 8 years from the point of PSA recurrence until mets become visible on a bone scan/CT. After the first met becomes visible, it may be, say, a couple of more years until the next met is detectable. The next one, say, a year after that. The number increases slowly at first, and then speeds up. This is called exponential growth. So if your first met is zapped, and you don't detect the next met for 1-3 years, was that because you zapped it or because the cancer's natural exponential growth just takes that long? That's why you need a random sample to compare it to. If the next met appeared more quickly in the control group on average, and the time difference was statistically significant, then perhaps there is a benefit. Because the benefit, if any, is thought to be small, large sample sizes are needed and the experiment has to run for a long time to detect a difference.

We do any treatment of metastatic disease with the hope of extending survival. As I said, oligometastatic treatment is not a new theory - you can read for yourself the 1995 paper cited in my article:

pcnrv.blogspot.com/2019/04/...

While ADT has toxicity, it doesn't kill 5% of men who use it.

So far, there has been no proof, and if you read the article you will better understand why the hypothesis is controversial.

407ca profile image
407ca

T A.

With all due respect I well understand lyour comment that reads " that all you see is all there is" . If you read my post I did not infer that. I do have mets and certainly have more as yet unknown. Of course there is more, that is why I clearly stated I am not cured. And yes, I well understand that what I believe may or not be true. My call, and the consequences are only on me. I never suggest anyone else do likewise.

With all that being said, the MDA oncologist, the Cleveland Clinic Radiologist and the European doctors are very astute. All are from leading institutions. All are published in peer review.

You may disagree with this but they see value so why not give it a go? I well know billions of circulating cells are there.

I have been at this for 13 years now . Been to M Embertons Tookad trial in London in 2007. I am not a SOC kind of guy. I never suggest this course for anyone, but if asked, will tell what I know from my own experience

Also, with respect, I suggest that the only way to gather evidence is to try new things. How do we get new therapies without someone trying something new? Maybe mot for everyone but good for me, and who the heck knows me better than myself?/

The oncologist at MDA flatly told me that ADT had yet to save a single life from 1941.

I already knew that.

So TA , I have the greatest respect for all you do here but I disagree on some points.

All the best

Tall_Allen profile image
Tall_Allen in reply to 407ca

I have seen all the same published data that they have seen - there is NO evidence of benefit yet. That doesn't mean that that there may not someday be some evidence. I have no idea what it is you disagree with - I am stating facts that are not open to disagreement.

SBRT to mets is not innocuous, as you seem to suggest ("Why not give it a go?"). In a recent small comparative trial, 5% of people receiving SBRT died from SBRT-related injuries. The way we find out new things is from clinical trials in carefully controlled conditions. Even with the most care taken, people are injured and people die. Participants in clinical trials are our heroes, often putting their lives on the line. Any doctor who does not carefully explain the risks does the patient a disservice.

My points obtain for TOOKAD as well as metastatic-directed therapy. See the section on morbidity of TOOKAD in this article:

pcnrv.blogspot.com/2017/01/...

I chose an experimental procedure for myself in 2010 (primary SBRT), but I knew the approximate risk of failure and the risk of injury before signing up. I was lucky it worked so well, and I have no lasting side effects.

407ca profile image
407ca in reply to Tall_Allen

Ok , I have chosen an experimental treatment for myself as did you for yourself. We both are well aware of the risks we take. So be it.

Is there no evidence? Well I guess that could be said of anything new. But, at some point, in any research, new opportunities become known. If this is not the case then why is it that you yourself tried something new? And, why is it that well respected doctors at MDA and other cutting edge places are looking at oligometastasis as treatable? Why not try something new as we all know that A DT has failed to cure anyone since 1941?

Tall_Allen profile image
Tall_Allen in reply to 407ca

When I chose SBRT there were 3 years of reported oncological and toxicity data. Also, SBRT was a "better mousetrap" version of IMRT, combined with the learnings about HDR brachytherapy monotherapy, on which there was published 10-year data (radiobiologically it was identical). Once a new alpha/beta ratio was established for prostate cancer (otherwise HDR brachy could not have worked), there were excellent radiobiological reasons why SBRT should work as well.

The idea of treating oligometastases is not "new." It was a hypothesis put forth by Hellman & Weichselbaum in 1995. Since then, there has been no evidence to support it. Read this:

pcnrv.blogspot.com/2019/04/...

I am certainly glad that clinicians are now designing experiments to test the hypothesis, but it does not matter what anyone believes, it is only facts that count. Those doctors can only express their personal beliefs, which does not count as evidence. It doesn't matter what institution they belong to. I'm sure they would agree.

ADT has not cured anyone ("curing" was never the goal), but at least in combination, there is excellent evidence that it extends survival.

Break60 profile image
Break60 in reply to Tall_Allen

TA and 407ca

Good thread. Thanks for sharing. I’ve had oligomets zapped by sbrt and at least at those sights have had no recurrence. At the same time I understand that it does not replace ADT but is complementary and MAY extend survival ( to be proven).

BAZZAD1953 profile image
BAZZAD1953

Hi cantChose

The brachytherapy is only for your prostate, it’s where they insert radioactive pellets into your prostate to kill the cancer in it. As far as your met’s are concerned it will be chemo or radiotherapy.

Regards

Bazzad1953

EdBar profile image
EdBar

I was dx with Stage 4 PCA mets to pelvis, sternum, ribs and spine along with several nodes. I had IMRT to the prostate and several nodes after beginning ADT for 6 months at the time of dx. This was recommended by an excellent radonc that I was seeing. After a lot of research it made sense to me to debulk the prostate similar to what is done with other cancers to reduce the tumor burden and the opportunity for it to spread to nearby areas or spin off more metastasis. Some of my old school doctors disagreed with this approach because of possible SE’s, others said it was a good idea. Dr. Myers once said it was one of the best moves that I had made early on in my treatment.

5 years later PSA is undetectable, scans show no active disease. I’ve also had ADT this entire time, and had chemo per CHAARTED, I view the IMRT as part of the multi-dimensional approach I’ve taken - so far so good. Given the choice I’d do it again in a heartbeat.

Ed

6357axbz profile image
6357axbz

Here is one study (cut and paste in google if link isn’t live):

thelancet.com/journals/lanc...

I showed this to my MDA RO who patiently read it with me and pointed out the rather severe adverse events.

“Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5–34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.”

AgedTenor profile image
AgedTenor

I was diagnosed 10 years ago. RRP and then radiation to the prostate bed failed to lower my PSA below 2.36. I then moved onto intermittent ADT (triptorelin) in 2011 when my PSA reached 10.2. For each of four cycles this lowered my PSA almost to undetectable with PSA rising in the off phases quite steeply. However, on the fifth cycle in summer 2016 it failed to drop below 2.27 so I went onto continuous ADT and over the next year it rose to 6.75. Early in 2017 I went to A&E (ER) with bowel pain. The bowel pain turned out to be wind but the scan they did revealed a large lesion on my T10 vertebra. I was declared suitable for SBRT and had very good treatment at the Cyberknife Centre in Harley Street in London. My PSA fell to 1.7 and then rose again but quite slowly till it reached 4.17 in February this year. Wishing to know where the main problem lay I persuaded my oncologist to recommend a PSMA scan which revealed that the SBRT had done a great job but that there was a further lesion on my rib but no evidence of mets anywhere else. I have now been approved for further SBRT, this time on the rib and I am very hopeful that this will give me a further extended period with good quality of life, though probably not a complete cure. The alternatives (chemo, abiraterone, etc) all come with probable increased side effects so I am hopeful that this is a good way to go. However, this approach is only thought effective for what is referred to as oligometastatic disease, defined as one to five metastases. I hope this helps. I should say that all this treatment has been covered by the health insurance which my wife pays for through her work in a London private school.

jfoesq profile image
jfoesq

I was riveted by the back and forth regarding the lack of scientific evidence versus the thoughts of highly regarded docs at well known institutions for IMRT or SBRT treatments. My well-respected doc at MSKCC had only 12 of his previous patients diagnosed with metPC have prostate removal surgery when I was diagnosed 7 yrs ago. I had a gleason 9, PSA in 40s and 4-6 mets.

There was no evidence that the surgery would help and although I believe the procedure has gained in popularity since then, I don't think there's strong/hard evidence yet to prove it helps and have it part of the SOC. But- I went into the surgery with my eyes wide open about the risks and the fact that it might not help. I weighed those risks and was willing to take them. And- I am happy I made that choice. While I am a true believer in the scientific method, evidence and proof, I don't think there is anything wrong with a patient pursuing a treatment that is offered to him, that has a scientific "theory" for why it may help, as long as all of the risks are known, understood , accepted and "reasonable". I think this is very different from trying a radical fly-by-night, shot-in-the-dark "treatment" where the risks are unknown. I was only 54 and otherwise healthy at the time and was willing to accept the risks. Having read the dialogue above, I am going to inquire about SBRT or IMRT (not sure of the diff) when I see my doc next week. I will be interested to hear her thoughts on the matter.

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