Seeking opinions on my Dad’s treatment options - low PSA metastatic prostate cancer

FYI- long post (my apologies).

Hi everyone - new to this forum and posting to seek other opinions/advice or simply hear similar stories to the one of my fathers. Providing all context as it’s been an atypical journey in his prostate cancer. Originally diagnosed Stage IV Gleason 9, BRCA 2 positive at 53 yrs old in 2016; had a prostatectomy a few months later. This didn’t work and he received rounds of Docetaxel and radiation, then a salvage lymphadenectomy when there were local mets. In 2017 he started Lupron, which he was on for 7 years with PSA remaining undetectable. He was truly unhappy with the effects of Lupron and since they considered him in “remission,” they allowed him to stop Lupron and monitor PSA more closely in the meantime. At the end of 2025 his PSA rose to .18 and he began Lupron again.

Speeding up to Feb 2026, he started experiencing excruciating pain, unable to move and resulted in a trip to the ER. The CT scan found lesions on his spine and we went to his doctor in Mayo, to then find after a PET scan that he had spinal cord compression and his cancer metastasized nearly over his entire body (shoulders, hips, spine, skull, ribs, lymph nodes…). He went through 5 rounds of targeted radiation on his spine to reverse the SCC as emergency treatment. The MO was highly suspecting small cell transformation, and he underwent a spinal biopsy, which the results showed PSA was negative on tumor itself but biopsy showed adenocarcinoma. Everyone was surprised as everything aligned with small cell due to very low PSA but vast spread of mets. However, his PSMA PET scan did show uptake of 29…weird.

We discovered he has a TMB of 12 and his MO asked for compassionate use of Keytruda, which he just received his 2nd round of. The MO wants to do another PET scan at this 5th treatment, which will be around 3 months since he started Keytruda. Basically I am seeking thoughts on:

1. A second opinion from MSK believed the Keytruda was not working and not high hopes that it would, since little evidence to be effective for prostate cancer and he has had increased pain in the areas of his cancer since 1st treatment. They said they would have treated 1st with a PARP inhibitor, but his MO at Mayo says the response rate would probably be only 6-8 months for it and it doesn’t penetrate blood brain barrier. So, he believes the best option right now is still Keytruda.

2. Other options we know of are PARP inhibitors, Pluvicto, or trying Docetaxel again with combo of carboplatin. Problem here is insurance will not approve Pluvicto until he has tried an oral androgen receptor (Xtandi) AND a PARP inhibitor. In order to have Pluvicto as a future option, they are starting him on Xtandi now to fulfill insurance requirements and then eventually adding in Talazoparib in combination. The issue here is the high toxicity that comes with that combo.

3. Wondering if it could still be small cell in other parts of his body, and the part they biopsied happened to just detect adenocranima? As we know, this could still be a possibility as well as stated by MO, but how many times would we want to put him under for more biopsies… but that would also change approach to his treatment.

Are there any other treatments we should be looking into? Or any other tests/scans, or markers to be aware of? For his prognosis- his MO told us if it was small cell, he thinks my father has 6 months to 1 year, and if it was low PSA but still adenocarcinoma, due to the aggressiveness, they would try to extend his life 1 to 2 years. Of course this is very heavy news and we also want to consider quality of life before sending him into these high toxicity combos of treatment when we were told his prognosis is so poor. But at the same time… he wants to fight this and are looking to seek as much information as possible to have all options laid out.

Thank you all for taking time to read this.