Dual Tracer FDG & Ga-PSMA PET/CT scans showing PSMA-negative tumor progress almost everywhere, what should be our next treatment ?

[mgaa]

Hi all, my father latest and first FDG/GA-PSMA dual tracer PET/CT is showing progress everywhere, including liver for the first time, he has lately done 3x Lu-177 sessions, the first 2 sessions took his PSA from 32.5 to 12.5 but then it continue to rise to 22 even after the 3rd Lu-177 session.

I understand that the PSA is no longer reflecting the progress of the disease.

before we continue to 4th Lu-177 session we had this scan so the first decision was to stop his Pluvicto treatment as it's no longer effective.

he was diagnosed with stage 4 metastatic Prostate cancer in 2020 and since then we've tried goserelin acetate implant shot every 3 months as a constant plus the treatments below:

-Bicalutamide (for only couple of months)

-Abiraterone (for nearly 10 months)

-Taxotere with and without Cisplatin

-Enzalutamide (for just 3 months without much success)

-Paclitaxel + Carboplatin (for just 2 months)

-Mitoxantrone

-Radiation

-3x sessions of Lu-177, last one was 6 weeks ago

-radiation on prostate a month ago.

This is the first time we do FDG PET/CT and the summary was:

studies reveal:

* Progressive course of the metastatic distant lymph nodes and osseous deposits.

* Newly developed hepatic, peritoneal and subcutaneous deposits.

* Regressive course of the prostatic mass and pelvic lymph nodes.

NB: The lesions show marked discordance with most of the disease burden becoming PSMA negative disease, denoting the de-differentiation of the disease.

We have no access to any clinical trials and we're not covered by any mean of insurance.

is there still any thing we can try ? any positive story with similar status ?

[GP24]

Usually you would get Cabazitaxel now. But your father already has so many treatments.

[Tall_Allen]

You've tried everything available in Egypt, I think.

[mgaa in reply to Tall_Allen]

we did a prostate biopsy prior to starting Pluvicto back in October 2024, can we use it to do genetic testing again to determine if PARP inhibitors or immunotherapy could be useful in that case ?

And what would be the next step if we can travel somewhere else for treatment ?

Thanks a lot for you

[Tall_Allen in reply to mgaa]

Metastases evolve, so you would get a clearer picture from a biopsy of his liver metastases. They would analyze it for histology, IHC, and genomics. They aren't likely to find anything useful.

PARP inhibitors are very toxic, so you would need assurance of a clear benefit.

[GP24 in reply to mgaa]

If the last genetic test was a blood test, testing the biopsy tissue can be useful now. One is a germline test and the other a somatic test. If they determine a BRCA mutation you could get Olaparib tablets.

[Seasid in reply to GP24]

Maybe with Abiraterone plus prednisolone or try dexamethasone if prednisolone is not effective? He had chemotherapy therefore maybe abiraterone plus prednisolone could do the trick? Olaparib is toxic I would only add if abiraterone plus prednisolone alone would not stop the progression of the cancer? I am not a doctor but I would definitely try abiraterone now as soon as possible.

[GP24 in reply to Seasid]

If he has a BRCA mutation, Olaparib will work very well. He is not in a situation where he can refuse drugs because of side effects.

As he has PSMA negative tumor, I am afraid Pluvicto will not be very effective. He did not have Cabazitaxel yet.

I think you would take Abiraterone plus Dexa right after becoming castration resistant after Abiraterone stops working, now it will no longer be effective.

[Seasid in reply to GP24]

I understand a situation. Therefore he could get a liquid biopsy like guardant 360 CDX and if they find any actionable mutation they could treat him accordingly.

My thinking was that if he had a chemotherapy since the abiraterone failure maybe abiraterone plus prednisolone could work again.

My thinking is based on the assumption that abiraterone plus prednisolone could still do some work and if it doesn't he could maybe add a parp inhibitor like olaparib or as you pointed he could now maybe try cabazitaxel and if he has for example BRCA mutation or similar present he could instead of olaparib maybe add carboplatin to cabazitaxel at least for 6 cycles.

My sister had taxol 150mg per m2 plus carboplatin 3 plus 3 cycles and all of this is very toxic.

That is why I was thinking at least to try again abiraterone which could be less toxic?

I understand that the situation is not easy. I don't understand fully why he is getting prostate radiation if he would be better of finding a system treatment which works globally instead of getting toxicity of a local treatment of the prostate which could further kill the bone marrow and prevent a systemic treatments?

Ok if he has symptoms and need local control around the prostate and still doesn't have a successful system treatment than maybe it is ok. I am not a doctor but my experience from this site is that you have to be very careful adding unnecessary toxicity because your treatments will finish when your kill your bone marrow that your thrombocites drop so much that you simply need to stop treatments because of that. I believe you can't solve the number of thrombocites by blood transfusions because they live only very short and as far as I understand (I am not a doctor) you have to simply stop all treatments if your thrombocites drop too much?

[mgaa in reply to Seasid]

Thanks a lot for your explanation

The situation before the latest prostate radiation was: Lu-177 is working and making progress and PSMA PET/CT after 2 sessions showed overall progress except for prostate, then it was the decision of the radiation.

After radiation was done and my dad overall situation got worse, we did FDG/Ga-PSMA PET/CT, and it revealed the current complicated situation.

I was naive and didn’t think that radiation on the prostate would affect bone marrow, which is already weakened by previous chemotherapy and Pluvicto.

You might also find some sub optimal decisions because of the availability of the treatments or the cost where there’s no insurance.

Thanks a lot for your input.