On ADT? No PSMA Scan for You

[ADTMan]

I just read an article that long term ADT greatly reduces the effectiveness of a PSMA Pet Scan. Based upon this I conclude that if you are ADT you won't be getting a PSMA scan. Can anyone confirm or deny this? If you go off ADT how long would you have to wait to get a scan, if at all? Would this limit the use of Lut 177 as well? Thanks.

[GP24]

I read that ADT can decrease the amount of detected tumor by up to 30%. It is unclear if the reason for this is that ADT makes the tumor shrink by up to 30%. The remaining 70% are still sufficient to get a successful PSMA PET/CT.

Almost all patients who get a Lu177 therapy now are on ADT.

[Hidden in reply to GP24]

But this would only be if you have detectable PSA, right?

[GP24 in reply to Hidden]

The PSA value and the PSMA expression are not linked directly. If you are NOT on ADT, the PSA value will indicate if there is a lot of tumor volume. If this is the case, this tumor volume will usually express a lot of PSMA and will then be detected with a PSMA PET/CT. If you are on ADT the tumor will shrink but not go away completely. The fact that it does not cause a high PSA value any more does not mean that the tumor no longer expresses PSMA. Probably a bit less but that is difficult to determine. So if you had a PSA value of e.g. 100 ng/ml before starting ADT, I would expect you will detect tumor with a PSMA PET/CT even when the ADT worked so well that you have an undetectable PSA value.

[ADTMan in reply to GP24]

The problem I foresee is that if ADT works by decreasing the ligand (receptor) that binds to the testosterone for use by the cancer cell, then the effectiveness of ligand directed therapy such as Lu-177 will be greatly reduced. Like radioactive iodine for thyroid cancer, Lu-177 should be given immediately after primary therapy. Perhaps ADT will be unnecessary if the Lu-177 takes care of all of the hormone sensitive cancer cells. Lets hope that ADT does not cause hormone sensitive cells to become castration resistant cells.

[GP24 in reply to ADTMan]

You write: "... if ADT works by decreasing the ligand (receptor) ..."

Based on the studies I read, this is not the case. For example the review Gran1234 has mentioned below

link.springer.com/article/1...

describes in detail that ADT increases the PSMA expression instead. They write: ".. based on 13 of the 19 reports, our analysis indicates that ADT increases PSMA expression [...] or may induce flare phenomena [..].

The remaining 6 studies add the following information: 4 described PSMA expression depended on ADT duration (2 groups concluded that PSMA increased with short-term ADT and decreased after long-term ADT [..]

and 2 other groups specifically mentioned that continuous long-term ADT decreased PSMA expression [...]).

So you apparently read a report with a minority opinion.

[ADTMan in reply to GP24]

The abstract for the article by the authors reads:

"Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMAPET/CT before starting ADT."

The PSMA ligand is a receptor. Since long-term ADT "significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT" is seems reasonable to deduce that long-term ADT does something to the receptor which makes it less likely to bind to the PSMA. Because Lu-177 is based upon attaching a radioactive source to PSMA to bind to the receptor is also seems reasonable that long-term ADT would reduce its effectiveness. I assume that this would also apply to other types of androgen receptor therapies such as enzalutamide, daralutamide, etc.

This brings up another interesting point. Does ADT actually cause hormone sensitive prostate cancer to die? My understanding is the consensus is "no." If it does, then that would explain the reduction of visible PCa -- it is due to fewer of them. If they do not die and mutate then this is bad. So the point would be to kill them off with Lu-177 while we still have a chance -- somewhat like radioactive iodine and thyroid cancer.

Thanks for your input.

[Gran1234]

Perhaps this article can help you:

"Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients"

link.springer.com/article/1...

[tango65]

It mainly applies to hormone sensitive cancer. There is a decrease of PSMA expression in hormone sensitive cancer with long ADT but there are still mets which are visible in a PSMA PET/CT making patients eligible for Lu 177 PSMA.

Castration resistant cancer expresses more PSMA and that may explain why patients with long term ADT and multiple treatment have some response to Lu 177 PSMA treatment and were admitted to the Vision and other clinical trials.