PSMA avid or not

[Blair77]

Reading through my husbands medical records I found that his cancer had been PSMA avid at dx in 2017. He participated in a trial with Dr. Hope at dx but dropped out after the first scan. I came upon notes that stated that on his study scan many more bone lesions and lymph nodes could be seen with the PSMA scan then on his PET scan that prompted his dx. At the time he was castration positive, I’m wondering if PSMA is changed when you become castrate resistant or if once your identified as PSMA avid you will always be PSMA avid? Does anyone know of data on this? Thanks!

[Tall_Allen]

PSMA does diminish over time on ADT, and men who have been castration resistant for a long time will have less PSMA on the surface of their cancer cells. There is also the issue of intratumoral heterogenity that has been noticed -- getting rid of only the PSMA positive cells allows the PSMA-negative cells to flourish. I think it''s a good idea, when the cancer has been metastasizing a lot, to get both a PSMA PET scan and an FDG PET scan before attempting PSMA-based therapy.

[Godblessus in reply to Tall_Allen]

Do you have a reference

[Roberthale7318]

I’m about to enter that same trail… Wondering why your husband dropped out after the first scan?

[Blair77 in reply to Roberthale7318]

At the time the scans were just for research but offered no path to treatment of any kind. He was having a hard time getting to the scans and was having claustrophobia issues also.

[HB1966]

Hello,

I can only tell you about my own experience.

In 2016 I had a PSMA-PET/CT and was strongly PSMA-positive. A lot of bone and lymph node metastases.

Now .... after 3 years of treatment with Zytiga, Xtandi, Xofigo, radiation etc. it looks completely different. Recently I had a PSMA-PET/CT and an FDG-PET/CT.

Unfortunately, very few PSMA-positive metastases are currently present.

Because of FDG-PET/CT many PSMA-negative metastases have been detected.

This means that PSMA therapy is not an option for me at the moment.

The next option is chemo with docetaxel / cabazitaxel.

Best wishes Theo

[Blair77 in reply to HB1966]

I’m sorry to hear that. Thank you for the information.

[Fairwind]

Every case is different..I have been fighting G-9 metastasized PC for 6 years..ADT and chemo both failed, PSA started doubling every 30 days, was up to 2300...Applied for the Vision (Lu-177) trial which required and paid for a PSMA scan which proved I was PSMA positive. bone mets only.. Was randomized into the Lu-177 group, and have had a very good response to it..Others are not so lucky..

[AlanMeyer]

Having read somewhere that Xtandi (aka enzalutamide) treatment increases PSMA expression (i.e. production of PSMA in the tumor cells) I searched Pubmed for ( enzalutiamide effect on psma ). Here is the result:

ncbi.nlm.nih.gov/pubmed/?te...

If I understand these articles correctly, enzalutamide and other androgen blockade drugs tend to increase PSMA expression, i.e., they cause the tumor cells to produce more PSMA in castrate resistant men than they had before. In some of these studies, patients were given enzalutamide for just 7 days and then tested for PSMA. There were significant increases in PSMA expression.

So, if I'm interpreting these abstracts correctly, it appears to me that your husband can increase the likelihood of benefiting from a PSMA targeted treatment (e.g., Lu-177) by taking Xtandi/enzalutamide, even for a short period.

Best of luck.

Alan

[Blair77]

That's great news!

[MateoBeach]

There are marked differences in response to short term androgen blockade between hormone sensitive and castrate resistant PC when used to try to enhance PSMA expression.

In the Australian study the hormonally sensitive had only 37.5% respond favorably with increased PSMA expression, while 62.5 % had reduction of PSMA expression.

But in castrate resistant PC there was consistent increased PSMA expression within 9 days and peaking at 23 days from ADT (LHRH +- bicalutamide) in ALL the men.

Response to enzalutamide may be stronger and different. this is being further studied.

But the implication for me is that the hormonally sensitive patient going for Lu-PSMA treatments may want to not introduce ADT drugs for their first treatment cycle, and go from there based on response. While the castrate resistant may reliably try short term enhancement of PSMA for treatments.

The other principle, as T_A has pointed out is that, while the addition of short term ADT/AR may enhance PSMA, long term ADT appears to decrease PDMA expression.

The ready availability of PSMA PET scans would be so helpful for all in sorting out individual treatment decisions. Especially when combined with FDG scan results. Hopefully we will not have too long to wait for Ga-PSMA PET scans to be approved in North America.

ncbi.nlm.nih.gov/pubmed/305...

PVC