It's prudent to get an FDG PET/CT at around the same time as the PSMA PET/CT.
Why Lutetium-177-PSMA treatment somet... - Advanced Prostate...
Why Lutetium-177-PSMA treatment sometimes may not help, and may even harm
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Tall_Allen
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Interesting.
"
Now that we know that heterogeneity can impact Lu-177-PSMA effectiveness, it behooves us to find a way of determining the degree of heterogeneity without doing a biopsy of every single metastatic site. One way is to give each patient two PET scans, so they could see the sites that exhibited PSMA expression as well as the sites that exhibited high uptake on an FDG PET scan.
It is futile to offer PSMA-targeted therapy if there are many sites that show up only on an FDG PET scan but few sites that display uptake of PSMA. It also may be futile to treat patients that show some sites where PSMA and FDG sites do not overlap - "discordant." On the other hand, where there is a high degree of overlap between FDG and PSMA - "concordant" - the PSMA radiotherapy will kill both cancers simultaneously. Of course, the ideal candidate would display only highly PSMA-avid sites. Thang et al. reported on the survival of 30 patients who were treated with Lu-177-PSMA (who were either high PSMA/low FDG or concordant, compared to 16 patients who were excluded based on lack of PSMA (8 patients) or a high degree of discordant sites (8 patients). All patients were heavily pretreated.
Treated patients survived 13.3 months (median)
Untreated patients survived 2.5 months (median)
It is unknown whether the survival of the excluded patients might have been longer or shorter had they received treatment. It is possible that discordant patients may benefit from sequenced (before or after) or concomitant treatment with:
chemotherapy
immunotherapy - trials of adjuvant Keytruda in UCSF and Melbourne; trials in Los Angeles, Europe & Australia, Germany, various US sites, and NY of a PSMA/ T cell-recruiting antibody + Keytruda; trial at UOP and Shanghai of a CAR-T/PSMA therapy
Xofigo for bone metastases - trial of a therapy that may include both
PARP inhibition - trial in Melbourne
other novel non-PSMA targeted treatments
It is possible that such adjuvant treatment may decrease the population of discordant sites, and minimize repopulation effects.
Based on this new knowledge, it is recommended that patients who are good candidates for Lu-177-PSMA radiotherapy have both a PSMA PET/CT scan and an FDG PET/CT at around the same time. FDG PET scans are generally covered by insurance; PSMA PET scans are not covered by insurance yet"
Ta
You have previously said it must be "FDG PET/CT"
But what does "FDG PET/CT" do that Auximin does not do?
FDG is a kind of PET that usually does not show up until later in progression when prostate cancer shifts from fat metabolism to glucose metabolism. This is also when PSMA often disappears. Axumin does not provide complementary information.
“Shifting from fat to glucose”. Does that mean that initially PC uses fat more than sugar in the begining? Dr shoulz had mentioned that PC uses fat and not like every other cancer that survives on glucose. Sorry, this is not the subject at hands but was just wondering
Yes, that is correct, usually.
Why did you quote that? Just click on the link.
To make it easier for people to follow.
To clarify, for the vast majority of people here. They're just lurking and attempting to learn.
A huge portion of the more useful content here, including all the acronyms, just goes by them.
So whenever I can, I try to help provide better context. Usually this is just spelling out acronyms that others are using.
That is most likely why I did the cut and paste.
I would be very grateful if you would point out any acronyms that are not defined in any article I write. I try to define them when I use them, but it is possible I miss some. Some, like ADT or PSA, should be well-known to anyone with advanced PC using this forum. Most are defined at this site:
prostatecancerinfolink.net/...
Most of the concepts are explained in detail in other articles that the interested reader can get more info on simply by putting the term in the search bar (e.g., "PET" or "Lu-177-PSMA").
You did not provide "better context," you just copied and pasted.
If you use Lu177 to treat early, you may see mets on a PSMA PET/CT but none on a FDG PET/CT. E.g. if you have non-metastatic CRPC. This is non-metastic if you test with CT/bone scan only but usually not if you use a PSMA PET/CT instead.
I prefer to have my tumor lesions treated early before they grow to a size that allows to detect them with a FDG PET/CT.
I would get a Lu177 treatment even in a discordant situation because I am satisfied when most of the tumor can be removed.
My dear friend is going to Germany soon for early treatment of his recurrent prostate cancer. He was highly PSMA-avid and highly-FDG-avid. Michael Hofman is analyzing his scans today. I'm hoping they are sufficiently concordant to not preclude Lu-177-PSMA treatment.
As I wrote, Lu-177-PSMA works just fine for about 2/3 of patients. It is easy enough to check for discordant tumors.
"I would get a Lu177 treatment even in a discordant situation because I am satisfied when most of the tumor can be removed." I guess you don't believe in repopulation. How can you possibly know what hasn't been treated if you only have a PSMA PET?
Dr. Hofman presented his approach to compare a PSMA PET/CT with a FDG PET/CT at the APCCC 2019 in Basel and made it popular this way. I agree that he will be having better results in his trials if he excludes discordant patients, but as a patient I would not want to be excluded from a Lu177 treatment. I want to be treated and see how it works out in my case. You always hope it will work well for you. If your friend gets to Germany he will be treated in any case because they do not compare a PSMA PET/CT with a FDG PET/CT. If he has a good response, fine. If he does not have a good response, a possible reason may be that he is discordant.
Yes, I am sceptical regarding the repopulation after a Lu177 treatment. It is a possible explanation but the tumor may develop differently than expected. I believe the tumor always gets enough food to grow, it does not matter much whether a number of cancer cells are removed.
If you are discordant you will know that the Lu177 therapy will only remove the mets you can see with a PSMA PET/CT. If this are 80% of the number of mets you see on a PSMA PET/CT and FDG PET/CT combined, I would go ahead to get rid of 80% of my tumor. And hope that this will be beneficial compared to keeping 100% of the tumor.
Frankly, I would try to convince an RO to remove the remaining mets with SBRT. Don't know if I will have success finding an RO for that. I read somewhere that this has been done already.
Actually, Matthias Eiber in Munich is also reviewing his scans. We will all conference tomorrow. Opinions have apparently changed since you were treated.
Repopulation is real phenomenon, known well to radiation oncologists. Tumors that are only partially treated may grow faster than if never treated. Cancer cells deep in tumors do not have good access to blood supply (tumor blood supply is leaky). Their growth is limited by lack of oxygenated blood and nutrients. They are also constrained by space - tumor tissue around the cells physically constrains its expansion outward. Opinions don't enter into it - it is a fact. Pick up a radiobiology textbook and read about repopulation (one of the 5 Rs of radiobiology).
In Germany most doctors, if not all, will treat you with Lu177 if your PSMA PET/CT shows mets, they do not ask for a FDG PET/CT. However, if you send Prof. Eiber a PSMA PET/CT and an FDG PET/CT and ask for a discordance evaluation he will do so. He is aware of the publications by Dr. Hofman. If you just send a PSMA PET/CT he will treat you and not ask for an additional FDG PET/CT before doing that.
If you are unsure if a Lu177 will work for you I would have a PSMA PET/CT after the first cycle already. Then you will see how it works and if a second cycle is worthwhile.
Yes, there are a few men who's disease will continue to progress although they were treated with Lu177. The waterfall plots in the various studies show this. However, I am not convinced that the Lu177 therapy made things worse. It could be that the disease would have progressed even more without the Lu177 therapy or the patient did not respond to the treatment.
Things have changed. Today, we had a conference call with Eiber, Hofman & Calais. They all looked at both scans. Eiber felt strongly about not treating my friend, due to heterogeneity and risk of repopulation.
I think you might want to read up on the radiobiology of repopulation.
Absent access to a good Radiobiology textbook. Here is a free series of online written lectures and videos that makes a good educational foundation. They are free and from ASTRO (American Society for Radiation Oncology). They were very useful for me.
I completely agree with you. Besides, all the treatments of metastatic prostate cancer have the same problem. You treat somebody with ADT and eventually the cancer starts growing again after a while. We can say the same for chemo, anti androgen and xofigo.
Furthermore there is not evidence Lu 177 PSMA treatment may harm a patient, in the sense of making the cancer worst and causing an earlier death of the patient. The title is misleading and it is going to lead to a lot of confusion among the members of this forum.
The difference between a narrow targeted therapy like Lu-177-PSMA or SBRT and a shotgun approach like docetaxel, ADT, Zytiga, Provenge or Xofigo is that targeted therapies intentionally only treat the sites they are targeted at (Xofigo is targeted at bone mets, but all bone mets).
Unfortunately, some very few men get a lot worse after treatment. You can see it in the waterfall plots of PSA change. The reason Hofman is pointing this out is because he saw it in his practice - not only did progression not stop - it accelerated after treatment. You ignore PSMA heterogeneity at your peril. Especially when it is a relatively simple thing to check - FDG scans are available everywhere. Repopulation is a well-known effect in radiobiology - look it up!
Am I understanding correctly that this PSMA targeted immunotherapy trial
clinicaltrials.gov/ct2/show... + Xofigo may work as well as Lu-177?
Not "+ Xofigo." Ra-223 does not form a stable chelate (molecule) with any of the PSMA ligands so far. Th-227-PSMA decays into Ra-223, and may detach from the PSMA ligand when it does. Ra-223 is the active ingredient in Xofigo and replaces calcium in bone metastases with active turnover. So you get a double bang for the buck when there are many bone mets. The Th-227-PSMA attaches to and kills any cell expressing PSMA. After it kills that cell, it can kill bone mets, even if they do not express PSMA.
pcnrv.blogspot.com/2018/10/...
Thanks for all of this info! We are looking at Heidelberg and just asked outside doc for fdg scan based on your info! Also very interested in this th227! Thanks again !
In your informative post, you indicated that
"Other opportunities for early use include Lu-177-PSMA treatment for those in the following settings: ....
salvage treatment after first recurrence
...
Centers in Germany may be willing to treat patients per protocol (i.e., outside of a clinical trial) in some of those situations
"
So here I am at 53 years old healing from RALP (10/14/2019). Six weeks after the procedure my PSA was 0.1 (not ultrasensitive test from Quest). My next PSA (the ultrasensitive kind) is in mid January (3 months after the procedure....it should be undetectable) . I was a Gleason 8, and I was SVI+. T3b N0 M0 So the chances of recurrence are 50/50 within 3 years and 80% within 10 years.
What makes this treatment so interesting is the relative lack of side effects compared to ADT/chemo/beam radiation of various sorts.
I have two (and a half) questions
1) Are the Dr's in Germany starting to treat this early in the journey? First recurrence?
2) Is it possible to get my removed tumor tested to see how PSMA avid it was and how much heterogeneity exists? or do I have to wait for it to actually reoccur and then sample that?
Tall_Allen in reply to
1. I don't know - ask them.
2. If you mmean your prostate tumor, that would be useless. PSMA doesn't show up much until it metastasizes.
Claud68 in reply to
In Vienna, Austria my husband got three Lu177 treatments after the PSA was rising fast in January 2019 after the RP in November 2018.
You can see some information on the website minute-medical.com, Prof. Dr. Markus Hartenbach.
Wife32 in reply to
My husband had his original tumor checked for psma expression tested after he recurred (18 months after surgery). They tested the stored tumor in Cleveland Ohio, and insurance paid for it.
Wow. I just read your article several times. It is a lot to absorb.
It does seem to complicate staging decisions though?
I think I might be too confused to even ask a cogent question. But I will give it a try.
Would a starting supposition of staging look something like this:
Lupron until early stages of castration resistance
Lu177
Cabotaxel / Zytiga
Thanks Tall Allen,
I just posted a reply to someone with rising Psa after Zytiga, and I mentioned Lu177 may not benefit everyone, but after reading the link pcnrv.blogspot.com/2019/12/….
about FDG PET/CT then there is a lot to think about when getting Lu177.
I was never offered FDG PET/CT scan, and its seemed Theranostics Australia may not have thought it necessary, but since I began Lu177 in Nov 2019, Dr Hoffman at Melbourne Peter Mac Hospital has had a lot more to say about FDG, and why some patients look like they should get a benefit with Lu177, but then do not.
But it can be said for certain that there is a continuing torrent of new information about Lu177 treatment and PsMa behaviour and testing and only a few doctors could fully understand it all, and apply the knowledge to a planned amount of appropriate therapy for optimal outcome.
I am in group of patients that Theranostic Australia docs are saying got a good response with Lu177. But my situation could change any time soon and I might be forced back to square one. Having Psa reduce from 25.0 to 0.32 seems like cancer reduction factor of 1/78, so my Pca is not giving me any symptoms. I have no idea where I will be in 12 months.
I may well have to take advice from doctors at Peter Mac in Melbourne.
They may be the most expensive in Australia, but not doing that may possibly would mean I'd die earlier than later. However, I think docs at Theranostics Australia would be keeping very close eye on latest Melbourne research findings to ensure they can offer an improved treatment with FDG relevance taken into account.
Patrick Turner.
Patrick
Peter Mac is a public hospital - as an Australian, why would you expect to be billed for any services you receive there?
Theranostics, on the other hand, is a private organisation, isn’t it?
Stuart
I made a mistake by assuming Peter Mac in Melbourne was a private hospital where you pay high prices of private medical care.
I just phoned their general enquiries phone number and the lady there said its all public and there is no section of that is for private patients.
Peter Mac is in Melbourne in state of Victoria, Australia, and I live in Canberra, 800km north of Melbourne, where I attend a public hospital where you pay no expenses for anything once you are admitted. I am amazed that a big well funded public hospital is gaining world acclaim for its work on cutting edge therapy for Pca.
Tall Allen below also refers to Dr Hoffman's work heading up teams to optimize nuclide therapy, aka radiopharmaceuticals, such as Lu177.
Regardless of whether I was going to get Lu177 soon after having a PsMa Ga68 PET/CT scan, I had my first such scan in May 2016, because it was already known it would most likely show up small mets 2mm dia well before any CT scan could manage.
I had a succession of such scans to watch Pca progression. It was November 2018 when I began Lu177 after a recent scan, but there was no mention made of me needing a FDG scan.
So far so good, I responded very well to Lu177, but I watched another man who had scans which predicted he should do well with Lu177, but then he hardly got any benefit and he died.
I don't take vacations. I'd be alone if I did. I am always thinking what next about my illness, and I am happy living right here, so I don't need vacations.
From what I have learned today, it looks likely I may end up being treated at Peter Mac if I wanted to if they convert the research into Pca into additional therapy for those with FDG or Pca that may not respond to Lu177.
After the stomach blockage from adhesions 3 weeks ago, I am on the mend,
and feeling real well today, able to work on my roof this am for 3 hours before it got too hot. I'm gaining weight, so tomorrow, the plan to get this here old athlete bloke back into good condition will continue, and I'll cycle at least 20km.
Always look on the bright side,
Patrick Turner.
Hi Patrick
Yes, Peter Mac is Australia’s only public hospital that is 100% devoted to cancer treatment.
Their R&D has always been well respected, but in the particular case of PSMA-related therapy they actually have the largest number of PSMA scanners in one lab anywhere in the world - I guess Australia’s relatively relaxed regulatory approach to nuclear medicine is responsible for that, and I dare say the Major US cancer centres will catch up pretty quickly once regulatory hurdles are overcome.
There’s a bit of ‘cultural cringe’ that leads many of us Australians to under-rate the ability of our local medical researchers - but in areas where they specialise, these guys really do excellent work.
Stuart
Indeed some kiwis sneak across the ditch to utilise it, at great expense!
This is part of the "growing pains" of all new therapies. We have a lot to learn about radiopharmaceuticals. I really admire Dr Hofman's groundbreaking work - he does so many prospective trials, adjusting as he goes. The first results from Germany, Australia, South Africa, etc. certainly whipped up a lot of enthusiasm (which will get the therapy and imaging approved in the coming years), and now we get down to the nitty gritty. Hofman reminds us that there is much about the natural history of PSMA (and non-PSMA-tumors) that we still need to learn about.
So TA, does this mean that someone like me, who is using a PSMA test simply attempting to determine if there is progression since a “vacation”, should also do the FDG Pet scan to look for metastasis that both do and do not express PSMA?
Schwah
It's only useful if you intend to get Lu-177-PSMA therapy immediately.
Outstanding report! Thank you Tall_Allen!
Very informative and timely for many! Thanks for your efforts and dedication TA!
Thank you Allen for this great summary. It is very timely for me now. I am interrupting my short term ADT adjuvant 6 weeks after IG-IMRT to hemi-pelvis with boost to two PSMA avid nodes. I am planning to go to Theranostics Australia in late February or early March after T levels restored and PSA at nadir. This because I am technically still HSPC and consultant felt off ADT would be best call for the first Lu treatment. He thought an FDG PET scan would be very low yield given the oligometastatic lymph-node HSPC status. But I am open to getting one and have run it by my USA MO and RO for their thoughts.
With much appreciation for what you do and offer us, -Paul
I agree that an FDG PET scan would probably be non-productive when one is still HSPC. However, I'm not sure whether PSMA-based therapy is a good idea or a bad idea for men who are HSPC- even if their cancer hasn't progressed to a glycolytic state, there is a risk in selecting for cancers that are non-PSMA-avid. Remember, over half the cancers that later became PSMA-avid were not so when the same HSPC-men were first diagnosed in Hofman's study. The question is - does the reduction in total cancer volume make up for the selective pressure? No one knows - only clinical trials can determine that.
Incidentally, a similar question arises for ADT - is early treatment of recurrent men more beneficial than waiting? Early evidence is that reducing the cancer burden with systemic ADT has a bigger effect than the selective pressure it exerts. Whether the same is true for PSMA-targeted therapy is anyone's guess at this point.
I read that Peter Mac was doing trial of Lu177 for some men where the initial treatment was with Lu177. There are/were conditions to be met before being accepted into the trial. Now it seems that may make sense where the Gleason score was high, and the Pca had already spread to prevent an RP and there was spread to distant sites, and if all these had PsMa avidity.
In my case I in 2009 I was Gleason 9, Pca prevented RP, even though Psa was only 6 at time of biopsy. I most likely had multiple distant mets, but all were HSPca, and ADT worked well to slow the growth of all my Pca until 2016, when Psa went up fast to 6. I had years where Psa lingered between 0.2 and 1.0, with no symptoms of Pca at all. But when Psa began to rise fast, this may have been the time when my Pca began to make high amount of PsMa to enable a PsMa Ga68 scan to begin to see mets because they were big enough, and making enough PsMa.
After failed Zytiga and then failed chemo, it seemed all my Pca was making a lot of PsMa to enable Lu177 to be effective.
Patrick Turner.
I would go for Lu177 now, while you are oligometastic. My treatments (4) killed off 6/7 PSMA-avid soft tissue lesions in 2017. It's reasonable to be wary of accelerated PC development following Lu177, but that is mostly a theoretical concept at this point. Kill what you can, in as many differing ways. R
Thank you for your support and perspective in this decision. Happy to hear you had such a good result. I am biased towards early aggressive treatments when toxicity is low as in this case. "Leave nothing on the table" that might help now approach. I guess cancer has taught me to say "Yes" to positive opportunities.
Me <===<<< As usual out of the loop and into my fruit loops....
Good Luck, Good Health and Good Humor.
j-o-h-n Monday 12/16/2019 6:13 PM EST
Thank you very much for posting this!
Interesting comments re Lu177 treatment following TA's post.
My first Lu177 treatments (4) were initiated 2.5y ago with PSMA -avid oligometastic soft tissue lesions. My PSA was then 1ng/ml. As in 4 months ago, I had a mixture of PSMA/FDG discordant and concordant PC with mostly pelvic bony mets. Hence, I have had palliative radiation (20Gy) locally, taking docetaxel currently and hope to hit the remaining PSMA-avid lesions that remain a few months down the track.
In general, I would use Lu177 as early as possible (especially for PSMA-avid soft tissue lesions).
I think in the future patients will be PSMA imaged (instead of or alongside MRI) to decide primary treatment (RP or RT) and any remaining micromets zapped with Lu177 or an alternative.
You might want to look at these trials to mop up the remaining PSMA-avid tumors:
clinicaltrials.gov/ct2/show...
clinicaltrials.gov/ct2/show...
Thank you. R
Tall Allen
As usual you are helping me to understand. Unfortunately you appear to be describing me. I completed the Lu 177 Vision trial three months ago Over the six infusions my PSA dropped from 1400 to 60. My scans were relatively unchanged.
In the last three months my PSA has moved to 414. I have been getting Jevtana with no apparent results. If things don’t improve on my next Dr visit in two weeks I will need a new strategy. Your thoughts are greatly appreciated.
Perhaps they can biopsy one of your faster growing mets, and they will be able to find something targetable?
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