PSA increase nearly one year after triplet therapy (mHSPC), what's next?

[Sissel25]

Hello everyone, thank you for all your help for a year. My dad went from a high of 3103 PSA to a nadir of 44. He unfortunately couldn't reach a <1 result but it had stabilized for a few months after his docetaxel + zytiga + prednisone. Unfortunately his new result is 67 PSA exactly a year since diagnosis.

His doctor had ordered a bone scan and bone scintigraphy before it increased because he still had pain on his right hip and we're meeting her on the 30.

What should we ask her and what would be some options to explore? He doesn't have BRCA mutation. All it says (might not be legible as it was in french) is variant "c.530C>G / p.(Pro177Arg) in exon 5 of the gene TP53( NM_000546.5)" if that means anything to you all

I've researched a bit but I don't know how to take a PSA increase like his considering his initial PSA diagnosis was so high.

It was also a very weird shift in PSA over the months. He started Docetaxel on February and his PSA had stayed around 99 for several months under chemo and then very slowly went down to 44 in August *after* his chemo.

Thank you for any tips and questions I could ask to his doctor. Maybe trials to consider? Thank you!

Edit: If that is any interest, he couldn't handle monthly injections of Degarelix (Firmagon) so he switched to Decaptetyl (Triptorelin) every 3 months and his PSA actually dropped further. Not sure if it's related though.

[PCaWarrior]

TP53 gene alterations are favorable for BAT.

TP53 and/or DNA repair (HRD) mutations necessary but not sufficient for BAT hyperresponse in the cypionate trials: Molecular and Clinical Characterization of Patients With Metastatic Castration Resistant Prostate Cancer Achieving Deep Responses to Bipolar Androgen Therapy - PMC

ncbi.nlm.nih.gov/pmc/articl...

“Responders were more likely to have had a radical prostatectomy as definitive therapy and were more likely to have been treated with an androgen receptor (AR) antagonist (enzalutamide or apalutamide) immediately before BAT (compared to abiraterone). Duration of prior enzalutamide therapy was longer in responders. Nonresponders were more likely to have bone-only metastases and responders were more likely to have nodal metastases. Assays detected ctDNA AR amplifications more often in responding patients. Responders trended toward having the presence of more TP53 mutations at baseline.” TP53/RB1 gene mutations in BAT hyper-responders: Clinical Efficacy of Bipolar Androgen Therapy in Men with Metastatic Castration-Resistant Prostate Cancer and Combined Tumor-Suppressor Loss – PMC

ncbi.nlm.nih.gov/pmc/articl...

If you are interested in this therapy, consult with Dr. Sam Denmeade - John Hopkins

[e-mail]

[Sissel25 in reply to PCaWarrior]

Thank you, but we are in France. Still, I will search and see our options around this topic.

[PCaWarrior]

Does he have mets?

If he is oligometastatic (1-5 mets) I'd ask about SBRT.

[Sissel25 in reply to PCaWarrior]

Widespread bone mets unfortunately. I'll still ask to be sure

[PCaWarrior in reply to Sissel25]

Wouldn't hurt to ask her about Pluvicto. My MO told me that in her clinical practice it usually doesn't make a big difference but sometimes it is amazing. One guy was about to go into hospice but tried Pluvicto first. He had an incredible response, and his PSA is undetectable.

There are a lot of trials available.

Supraphysiological Androgen to Enhance Chemotherapy Treatment Activity in Metastatic Castration-Resistant Prostate Cancer, SPECTRA Study - Full Text View - ClinicalTrials.gov

classic.clinicaltrials.gov/...

BAT trial (Sipuleucel-T Combined With Bipolar Androgen Therapy in Men With mCRPC)

clinicaltrials.gov/study/NC...

This is a nice one but is in Brazil: Extreme Bipolar Androgen Therapy With Darolutamide and Testosterone Cypionate in Patients With Metastatic Castration-Resistant Prostate Cancer (ExBAT Trial) - Full Text View - ClinicalTrials.gov

classic.clinicaltrials.gov/...

Some of these trials might exclude prior taxel therapies.

[Tall_Allen]

Can he get Xofigo?

[Sissel25 in reply to Tall_Allen]

I think he can and might be reimbursed by our healthcare system in France. I will ask about that, thank you.

[PCaWarrior]

This trial combines Xofigo and BAT. You're in France but something to follow? medifind.com/articles/clini...

[Benkaymel in reply to PCaWarrior]

Given that he has pain from the bone mets, I wouldn't think BAT is a viable option for him is it?

[PCaWarrior in reply to Benkaymel]

May or may not. Denmeade is the guy to ask.

[Aldo62]

I have been doing Orgovyx (ADT) along with Nubeqa (Darolutamide) and it seems to be a very effective combo, with fewer side effects than ADT drugs like Lupron. Orgovyx lowers the T, and Nubeqa blocks the T receptors inside the cancer cell. They are both very expensive drugs, but I have been able to get them for free through the hospital.