Psma addition

Posted by whatthef @whatthef, Sep 15 7:33am

My oncologist communicated a newly fda approved treatment for metastatic prostate cancer called “psma addition” for pc that is not resistant to therapy. Has anyone applied this therapy or has any info on this therapy? Thanks

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Profile picture for Too-Many @toomany

@mjp0512 Doh! Thanks, MJ. I missed that little detail somewhere. My bad.

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@toomany - 😁 No worries. You only had to read it twice. I have to read stuff 4 or 5 times sometimes before I get it. It's exhausting. 🤣

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Profile picture for mjp0512 @mjp0512

@toomany - 😁 No worries. You only had to read it twice. I have to read stuff 4 or 5 times sometimes before I get it. It's exhausting. 🤣

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@mjp0512 Not exactly sure, but doesn’t the success of Pluvicto directly rely on PSMA expression?
In other words, aggressive disease in a low PSA setting might not be effective due to lack of PSMA on the outside of the PCa cells? Your PET would not look like the proverbial Xmas tree…maybe a few twinkles here and there.
I think this may have been discussed way back when, but I don’t remember…
Phil

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Profile picture for Too-Many @toomany

@lag Thank you, but right or wrong, the first part of this statement, is inconsistent with my own current understanding. Again, perhaps my understanding of the term "metastatic" is wrong, but the glycoprotein PSMA, is said to be present on the surface of 'ALL' prostate cancer cells (not just the "metastatic" ones), right? I myself am classified as localized "non-metastatic", but my PSMA-PET scan results, show an abundance of radiotracer uptake, bound to the PSMA protein in "localized" (non-metastatic) cancer cells.

Otherwise, yes, Pluvicto apparently does indeed target that surface (PSMA) protein.

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@toomany Sorry--in my husband's case, the PSMA avid sites targeted by the Pluvicto were all metastases on his spine, hence my focus on metasyptases. But it is true that Pluvicto seeks out all PSMA avid sites which express a high enough level of PSMA.

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Just to be clear, not all prostate cancer cells express PSMA to a sufficient extent for Pluvicto to be effective. Hence, a PSMA scan is often done to determine if Pluvicto would be the best approach.

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Prostate cancer is present in most 90-year-olds who are autopsied and have died of natural causes. There is ordinarily no reason to treat them; surveillance is the operative word. The PSMA PET/CT scans determine the presence of cancer outside of the prostate gland, i.e., metastasis. The 'radioligand' [Lutetium-177] treatment is very expensive. It is effective in preventing progression of metastatic disease for both hormone-insensitive and hormone-sensitive disease. Initially, it was restricted to hormone-insensitive patients who had gone through chemotherapy as well. Authorised uses are progressing backwards. I suspect trials are already ongoing for non-metastatic (gland-limited) disease. It appears they now know who, genetically, will be great, medium, and poor responders to the currently approved radioligand treatment. Others are in the pipeline, likely with different response rates.

PS: I believe Johns Hopkins was studying a strategy to reduce metastatic disease with three injections of a therapeutic vaccine into the gland. Would it be an interesting add-on to combine approaches in one of the study arms? There might be an additive benefit.

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Profile picture for lag @lag

@toomany Sorry--in my husband's case, the PSMA avid sites targeted by the Pluvicto were all metastases on his spine, hence my focus on metasyptases. But it is true that Pluvicto seeks out all PSMA avid sites which express a high enough level of PSMA.

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@lag Thanks you, but no apology is necessary. I understand completely. I believe Pluvicto is restricted to patients who are verified "metastatic", because its been ruled-out in my case, and yes, I believe it (Pluvicto), binds to the PSMA surface protein found on cancerous cells, 'wherever' it is found in the body, regardless of its concentration or prevalence (i.e., whether the amount of PSMA is weak or strong, local or remote, etc.

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Profile picture for thmssllvn @thmssllvn

Prostate cancer is present in most 90-year-olds who are autopsied and have died of natural causes. There is ordinarily no reason to treat them; surveillance is the operative word. The PSMA PET/CT scans determine the presence of cancer outside of the prostate gland, i.e., metastasis. The 'radioligand' [Lutetium-177] treatment is very expensive. It is effective in preventing progression of metastatic disease for both hormone-insensitive and hormone-sensitive disease. Initially, it was restricted to hormone-insensitive patients who had gone through chemotherapy as well. Authorised uses are progressing backwards. I suspect trials are already ongoing for non-metastatic (gland-limited) disease. It appears they now know who, genetically, will be great, medium, and poor responders to the currently approved radioligand treatment. Others are in the pipeline, likely with different response rates.

PS: I believe Johns Hopkins was studying a strategy to reduce metastatic disease with three injections of a therapeutic vaccine into the gland. Would it be an interesting add-on to combine approaches in one of the study arms? There might be an additive benefit.

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@thmssllvn Greetings! Regarding your following statement. . . . "Prostate cancer is present in most 90-year-olds who are autopsied and have died of natural causes."

This statement appears to be absolutely true. In fact, my original radiation oncologist (in 2018), once told me that it was very likely that every single man on planet earth over the age of 70, had (or has) prostate cancer of one form or another (mild and dormant, active and aggressive, or something in-between), and he was adamant about it! He pointed to a published, but (as I recall), a somewhat 'dated' article from the Detroit, Michigan (?) area (maybe Warren County?), or thereabouts, wherein a group of researchers, went back and looked at post-mortem prostate tissue samples, from a huge number of males of all ages (like age 12-90!), regardless of their cause of death, and reported that a vast percentage of them showed "cancerous" cells of the prostate.

I regret that I don't have a firm or better memory of the details, or a link to that actual article, but let's just say that I recall it making an impression on me at the time!

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Profile picture for heavyphil @heavyphil

@mjp0512 Not exactly sure, but doesn’t the success of Pluvicto directly rely on PSMA expression?
In other words, aggressive disease in a low PSA setting might not be effective due to lack of PSMA on the outside of the PCa cells? Your PET would not look like the proverbial Xmas tree…maybe a few twinkles here and there.
I think this may have been discussed way back when, but I don’t remember…
Phil

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@heavyphil - You’re probably right Phil, but to be honest, I stopped researching Pluvicto when my genetic testing (both somatic and germline) came back with a TP53 mutation. Since Pluvicto does not play well with TP53, why put myself through that with such marginal success. Oncologist already knows it’s a no go even if it’s the last tool in the box.

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Profile picture for mjp0512 @mjp0512

@heavyphil - You’re probably right Phil, but to be honest, I stopped researching Pluvicto when my genetic testing (both somatic and germline) came back with a TP53 mutation. Since Pluvicto does not play well with TP53, why put myself through that with such marginal success. Oncologist already knows it’s a no go even if it’s the last tool in the box.

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@mjp0512 Sorry, Mike, did not know about the mutation.
Phil

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Profile picture for heavyphil @heavyphil

@mjp0512 Sorry, Mike, did not know about the mutation.
Phil

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@heavyphil - No worries, my friend. Just another one of those "it is, what it is" things.

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