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Biochemical Relapse After Lu-177 PSMA — Options for Bone-only mCRPC
My father is 82 and was diagnosed in December 2021 with advanced prostate cancer. MRI at diagnosis showed a PIRADS 5 prostate lesion with pelvic lymphadenopathy and multiple bone metastases. No biopsy done. A PSMA PET in 2022 confirmed diffuse skeletal disease. His PSA was >100 at presentation and ALP was ~300.
In January 2022 he underwent orchiectomy and started abiraterone, which he continued for about 20 months. His PSA fell into the 20–30 range and remained stable during that time. ALP normalized and has stayed normal since. He has been on denosumab 120 mg every 12 weeks throughout.
In late 2023 his PSA began rising (into the 40s), marking transition to castration-resistant disease, and he was switched to enzalutamide. PSA initially dropped to 19 but then gradually increased despite dose escalation. He was on enzalutamide for roughly 12 months. By August 2024 PSA was 58 and by September it reached 130. Around that time he developed intermittent bone pain. A repeat PSMA PET showed more extensive skeletal metastases but resolution of the prostate lesion and pelvic nodes — essentially bone-only disease at that stage.
He then received 4 cycles of Lu-177 PSMA starting September 2024, and hormonal therapy was stopped at that time. He had an excellent response, with PSA declining to a nadir of 2.4 about six months after completing Lu. Bone pain resolved and he returned to his usual routine. He is currently not on any systemic cancer therapy.
Now, about a year after finishing Lu, his PSA has risen gradually from 2.4 to 7.5 over five months. He feels well, walks over a kilometer daily, and continues part-time office work. Hemoglobin is around 12 and ALP remains normal. Due to age and reduced cardiac function (EF ~35–40%, CRT device), he is not considered a candidate for standard chemotherapy.
I am trying to understand realistic next options now that his PSA appears to be rising again. For those who have been in a similar situation after a strong Lu response, what approaches have provided meaningful control? Has anyone had success with Lu rechallenge (2 or 4 more cycles), Actinium-based therapy, Radium-223, or any oral agents in older patients who cannot tolerate chemotherapy? Would appreciate hearing how others have sequenced treatment at this stage.
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@sumith
That’s why I mentioned speaking with your doctor about it. I also have no chance of using it, with my BRCA2 genetic problem my PSA rises very quickly If I even cut back on the ARPI drugs.
Hopefully Pluvicto will work again for him, After that low-dose chemo may work.
@jeffmarc - what about Darolutamide? Would'nt this work in this case to manage the disease?
@sumith - have you discussed this with the medical onco?
@sbd
While I am really in favor of Darolutamide treatment, since it has so a few side effects And works so well for me, he did have Enzalutamide fail on him. As a result, it is very unlikely that Darolutamide is going to work. He also failed abiraterone, so at this point, the only remaining treatments are chemo and Pluvicto.
I wish there was something else that could be done, This is what many of us are worried about, When they ARPI drugs, fail, there may be no further adequate treatment Besides chemo and Pluvicto. Yes BAT is an option for some people, but not for him.
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2 Reactions@jeffmarc, since you are BRCA 2 postive, you also have the option of using Olaparib right?
@sumith
That is true for me, but not for @sumith since he doesn’t have BRCA2.
@jeffmarc, do you know of people with metastatic PCA in the 80 plus age group who opted for low dose Docetaxel after exhausting all other options (including Pluvicto), and did reasonably well after that (in terms of quality of life, survival etc)? Basically, want to know if the benefit of low dose chemo at this stage outweighs it's toxicity risks.
FWIW, I am in a similar situation in that ADT/ARSI has become less than effective and I am a heart failure patient as well. (EF 35%). I met with my Cardio-oncologist 2 weeks ago who said that while chemo may affect heart function, Docetaxel has a low cardiotoxicity profile and would be the preferred chemo drug should my Genito-urinary and medical oncologists agree that chemo is necessary. Due to genetic profile, I am not a candidate for Pluvicto.
@sumith
I know a lot of guys over at ancan.org That are on Nubeqa Alone. Many of them in there are in their 80s or late 70s. I am not sure if any of them are taking the lower dose of it. I have heard one person talk about it, You could attend one of the meetings and ask about it. Just signing up for the advanced prostate cancer meetings gets you a newsletter every week that has a whole bunch of information on new things going on in treatment.
I also attend CSC meetings and one guy moved to South Africa and is now on just Nubeqa And it’s working great for him. He has a very extensive case with a Gleason nine And he had a lot of metastasis to start.
@jeffmarc, my dad will not respond to Nubeqa (darolutamide) since he is already resistant to Enzalutamide. I was asking about the safety and efficacy of low dose Docetaxel (chemo) at his age.
@sumith
I am unsure why you are asking this. You’ve already said he won’t respond to Darolutamide Because he has already Failed Enzalutamide.
In that case going to Darolutamide Is probably not going work at all, and a low-dose of it won’t help.
I know people in their 80s that are using Darolutamide As their only drug and it works great for them. So the safety of the drug is not a problem, the Efficacy of the drug is what Is questioned whether it is a full dose or a half dose.
The two drugs are too similar.
This is a case where you could try BAT. Giving testosterone injections for a few months to see if it will reset the ability for a lutamide drug to work. It works for about 50% of people. The injections of testosterone would definitely make him feel better. The question is, will it raise his PSA too quickly and defeat the purpose.
There are a couple of BAT articles. The second one has a bunch of stuff about treatment of advanced prostate cancer as well.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9313844/
https://online.flippingbook.com/view/150884930/2-3/