Is my father's PCa becoming castration resistant?

[calcifer24]

Hi all,

This is my first post here. My 66 year old father was diagnosed with metastatic PCa in April 2024. Initial PSA was 35.6, Gleason 5+4. A month later, PSMA-PET showed widespread mets in the tissues surrounding his prostate, including bones and lymph nodes. He did not have mets in his head, neck, liver, or lungs.

He was entered into AstraZeneca's Saruparib (AZD5305) trial and was given Zoladex, Enzalutamide, and either Saruparib or placebo. Within two months his PSA went from 35.6 to 1.05. For the next ~6 months his PSA kept going down and reached 0.09. Bone scintigraphy every 16 weeks showed significant reduction in all mets.

Unfortunately, PSA started to increase in January 2025. The next 3 months it went up to 0.15, 0.25 and most recently 0.65, a few days ago. That last one feels especially worrying since it's a 160% increase month-over-month. I was told doubling times below 3 months are usually bad and the idea that ADT might stop working now, when it's not even been a year, is terrifying.

As part of the clinical trial there is a PSMA-PET every 48 weeks, which is coming up at the end of April. I guess we'll know if / how much the mets have spread. Do you guys think it has become castration resistant? How soon would he be looking at chemo? I know nothing is curative at this stage. I'm just clinging on to any hope for retaining his quality of life for as long as possible.

Thank you so much, and I wish you all the very best with your treatments.

[Mgtd]

So sorry you and your dad are experiencing this. The roller coaster ride of this cancer is definitely the most difficult part on the family.

Has he been released from the trial? Do not give up hope there are other avenues that a medical oncologist and a palliative care doctor can recommend.

Wishing you both calm seas going forward.

[calcifer24 in reply to Mgtd]

Thank you for your reply. He hasn't been released from the trial yet. His oncologist said they should talk after the PSMA-PET next month. My dad said the doctor was averting his eyes when he said that, so I don't think it'll be good news.

I assume he'll have to start chemo, and I told him to bring up Bipolar Androgen Therapy as well. We'll see how it goes...

[j-o-h-n in reply to calcifer24]

Greetings calcifer24,

Where is your dear Dad located (City/State)? Ask here if you need the name of a "better" (or second opinion) M.O. located in his area. We all wish your DAD well and commend you for being a great offspring. Keep posting here!!! (BTW to address you properly are you a male or a female?)

Good Luck, Good Health and Good Humor.

j-o-h-n

[calcifer24 in reply to j-o-h-n]

Greetings John! My dad and I (also a man) are in Europe, but in different countries. I'm happy to consider any options within Europe, though travelling to the US would be difficult and hopefully shouldn't be needed.

Thanks for the well-wishes, I wish you the best of health as well!

[petabyte in reply to calcifer24]

It's probably not your first concern but consider germline genetic testing for you and your father when you can. You should also screen regularly.

Having a close relative with prostate cancer increases your risk.

What countries are you each in?

I just looked up the trial and it looks like genetic testing is part of the protocol for your father.

[calcifer24 in reply to petabyte]

Ah, I should have mentioned that! He did have genetic testing which revealed that he has a mutation on the ATM gene called ATM c.9023G>A. I'm in the UK and on an NHS waiting list to get tested. I'm in my late 30s now and will start regular prostate exams at 40.

[Boltonlanding in reply to calcifer24]

I brought up BAT with my oncology nurse on last visit and she had not heard about, so didn't think their practice used it. She was going to bring it up to my doctor as a possibility. It is my understanding that its not a well known or used treatment, even though it has been used in trials for 10+ years with some success ! Maybe because it's not a big money maker !

[Tall_Allen]

Castration resistance is a spectrum, not an either/or kind of thing. His PSA is still low.

[Tinkudi in reply to Tall_Allen]

So Allen if psa is still low but on a rising trend , when does one change the treatment plan of adt plus ARPI , if otherwise doing well ?

[Justfor_ in reply to Tinkudi]

When some magic number is breached and this triggers a wake-up call to a lazy doc.

[Tall_Allen in reply to Tinkudi]

I don't know what you mean by a "rising trend." But if PSADT is under 9 months and PSA> 1.0, and there is growth inimaging-detected metastases, it is time for docetaxel.

[Skilover]

I lack the knowledge to state whether he is becoming castrate resistant but I am curious why he opted for a trial over SOC (which in the States is triplet therapy)? Is doublet or triplet therapy available to him IFFFF the trial stops working for him? Good luck!

[calcifer24 in reply to Skilover]

Thanks! He opted for the trial because the oncologist running it came highly recommended (my dad is a retired doctor himself so these references were personal) and AstraZeneca was covering the cost of his entire treatment, not just the trial drug, so it became the obvious choice. If (when?) when he's removed from the trial doublet/triplet should still be an option as he's never had chemo before.

There is also the fact that Saruparib had already been approved for castration resistant prostate cancer with some great results. So we knew the drug was good. The trial is only to see if starting the drug before the cancer becomes castration resistant improves the prognosis.