Treatment for low-PSA mHSPCa

[Purple-Bike]

Does anyone have a clue for treatment of low-PSA metastatic PCa? For neuroendocrine PCa?

The only study I can find on treatment for low-PSA: "Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels: A Meta-Analysis | Oncology | JAMA Network Open"

| indicates that adding docetaxel to SOC for low-PSA patients had very good results, however this was for non-metastatic advanced localized disease.

From European Urology Volume 74, Issue 2, August 2018, Clinical and Genomic Characterization of Low–Prostate-specific Antigen, High-grade Prostate Cancer

"For Gleason 8–10 tumors, PSA ≤2.5 ng/ml was associated with higher expression of neuroendocrine/small-cell markers compared to >2.5 ng/ml (p = 0.046), with no such relationship for Gleason ≤7 disease".

[GP24]

You do not seem to have neuroendocrine PCa, so why do you ask?

The usual threapy is a chemo with carboplatin combined with e.g. cabazitaxel: ncbi.nlm.nih.gov/pmc/articl...

This study reports success with metastases directed therapy for neuroendocrine PCa: ncbi.nlm.nih.gov/pmc/articl...

Finally, Himisha Beltran and Martin Bakht found that some neuroendocrine PCa has PSMA expression. So if a PSMA PET/CT shows PSMA positive lesions you could try Lutetium 177 therapy. (Experimental) urotoday.com/video-lectures... and pubmed.ncbi.nlm.nih.gov/315...

[Tall_Allen]

"Does anyone have a clue for treatment of low-PSA metastatic PCa? For neuroendocrine PCa? "

Is that your diagnosis? Which one do you have - low-PSA metastatic PCa or neuroendocrine PCa or both? How was it diagnosed?

[Purple-Bike in reply to Tall_Allen]

CT and Bone Scan show two focal uptakes, with more precision from DCF-Pyl-PET and NaF-PET scans that are to be made within three days when I will also get a set of tests to indicate whether my low-PSA score is likely to be associated with neuroendocrine disease.

May I change focus…..? MO did not order an FDG-PET scan, but the passages below make me think this could be a mistake. Should I insist?

Posted by V10fanatic: “My recent PSMA-PET came back clear with a PSA of 4, so my MO suggested I run an FDG. It found 4 mets; my spine(2), rib, and pelvis. He said that maybe 10% of metastatic men fall into the discordant realm”.

From A Comparison of 18F-DCFPyL, 18F-NaF, and 18F-FDG PET/CT in a Prospective Cohort of Men with Metastatic Prostate Cancer J Nucl Med 2022; 63:735–741 DOI: 10.2967/jnumed.121.262371

“In about 10% of men, some lesions were positive on-FDG and negative on DCFPyL, despite an overall higher lesion number seen on DCFPyL, implying that a limited number of metastases may exhibit aggressive metabolic features with low PSMA (FDG+, PSMA–) earlier in the course of disease (22). Indeed, similar to the study by Wang et al. (23), we noted discordance between the 2 scans with 22 of 322 lesions detected by-FDG alone in 8 of 30 patients (27%), of which 3 were CRPC and 5 were CSPC. These lesions may be clinically relevant, as decreased survival and therapeutic response have been noted in men with abnormal FDG PET findings (21, 22,24,25)”.

[Tall_Allen in reply to Purple-Bike]

Why? Are you getting Pluvicto?

[Leaffan57]

I’m low volume metastatic… getting ADT and Erleada

[Purple-Bike]

LU-177 J591 is one of the options I am considering.

But even if I will not use that therapy, surely an FDG PET scan will be crucial, if lesions unique to FDG-PET are discovered, given that I will use SBRT for local control?

It is only 10% of men who have lesions only shown on FDG-PET, but I could be one of those 10 % and it also seems that those kinds of lesions are of higher potential lethality.

[Purple-Bike]

Unfortunately, there was no comparison between FDG-PET and NaF-PET, which might have been more interesting given that neither need PSMA-expressing cancer cells for detection. Perhaps the 10 % figure would be much smaller in such a comparison, so that it is not worth worrying about, given that I will have both NaF-PET and DCF-Pyl..... Also the CT scan, FWIW, detects non-PSMA avid cells.