Connect
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.
Like
Helpful
HugInterested in more discussions like this? Go to the Prostate Cancer Support Group.
Connect
You are running into a problem many of us are worried about having. We’re waiting for the next possible drug that can treat people when the ARPI‘s fail (enzalutamide, etc).
If the new metastasis are strictly to the bone, then radium 223 (Xofigo) is an option that can be considered.
The only other option at this point is chemotherapy. Has this been discussed with your doctor? You say he can’t tolerate it, but it may be the only choice.
I know someone who went to Austria to get actinium, It is available in the United States, but it is hard to find since it is only under a clinical trial. It might make a difference, I know people who have had a second Lu-177 Set of treatments, Insurance paid for it because they were the first one under the clinical trials. It is being done in some foreign countries as well. The problem is, it doesn’t have a high percentage of success for the long-term, I would think since it failed so quickly they might not consider it.
-
Like -
Helpful -
Hug
4 ReactionsOne thing I had not considered Is clinical trials. There are some that might work for him. You need to speak to your doctor about this, preferably an oncologist. Going to a center of excellence could get you a better chance of finding an appropriate clinical trial.. This is something that’s worth looking around for. Not sure if he can get into a trial, but his situation is at the point where that may be the best solution.
-
Like -
Helpful -
Hug
1 Reaction@jeffmarc, thanks for your insights. Yes, we did discuss the option of taking chemo before we went ahead with Lu. Given my dad's age, the oncologist had mentioned low dose chemo, but wasn't sure if it would help much.
@jeffmarc, I agree. We are in India, and am not sure if there is any such trial here that is recruiting new patients. To buy some time, we probably might go ahead with 2 more cycles of Lu. Does that sound reasonable?
@sumith
1/3 of people get really good results from Pluvicto, 1/3 people do OK on Pluvicto And 1/3 of people get no results at all.
It sounds like your husband’s in the middle group. It may help a little, but I doubt it’s going to work for long because it didn’t the first time. If you were to do this kind of treatment again, you may want to do actinium instead. It does cause problems with dry mouth, You should speak to the doctors about it if that’s what you want to consider. I am not sure it’s available where you live. You could travel to another country to get it.
-
Like -
Helpful -
Hug
1 Reaction@sumith
Low-dose chemo actually does work better than you think. The thing with doing low-dose is that you end up giving the same amount of chemo as you would to somebody that was getting normal doses but you just get more doses over a longer period of time. Speak to your doctor and find out if this is true where you are at. The end result is supposed to be quite similar.
@jeffmarc What about Bi-Polar Therapy when all else fails? Maybe a huge dose of T would shock the cancer cells?
We’ve discussed this on the forum and there are threads here you can search for more info. Also, it would be a lot easier and less expensive to do. Best of Luck,
Phil
@jeffmarc, it's available where we stay. 4 cycles brought the PSA down from 130 to 2.4. PSA has now started rising (7.5 currently), a year after the last cycle of Lu. So it might be worth trying another 2 rounds if PSA continues to rise?
@sumith
The normal treatment Is to have six rounds of Pluvicto. Definitely sounds like you should do the other two.
You could try the bi-polar therapy @heavyphil recommended. That can reset the body so that drugs like Enzalutamide Can work again. Doesn’t work for everyone and could raise the PSA quite quickly for some people. Another thing to speak to your doctor about.
-
Like -
Helpful -
Hug
1 Reaction@jeffmarc, bipolar therapy sounds promising, but the doctor here says it may not be an option for my dad since he has multiple spinal and pelvic metastases (atleast in the last PSMA scan) including a biggish one at L4. Also, the last time his PSA rose, he had back pain and found it difficult to stand or sit. Given this response, I guess we wouldnt want to risk a flare or worse, a fracture in the spine.