Help Me Understand This

[ADTMan]

acsjournals.onlinelibrary.w...

This article contains the following statement: "22% of our patients developed metastasis in the presence of an undetectable PSA." Dr. Kwon said the same thing in his recent YouTube video.

If this is the case, why are PSMA scans available only to people who have failed primary therapy with a rising PSA? People in the high risk and very high risk categories with significant probability of spread outside the prostate should be given a PSMA scan as the standard of care.

When 22% or 1 in 5 people are at risk of metastasis and don't receive a PSMA scan until they exhibit clinical signs something needs to change.

[Hidden]

Its not 22% of the total number if patients in that retrospective study. its more like .2%. 10 out of over 4000 patients had metastatic progression despite having undetectable PSA. Small cell cancer is a bitch to a very small number of overall patients. And Kwon did say in a video that up to 12% of his patients had metastatic progression despite an undetectable PSA, but I am assuming that number is because he has a concentration of serious cases. His next slide was about the tests they use to identify neuroendocrine. Generally, PSA is the best guide to cancer progression, but as you correctly note, not always.

[ADTMan in reply to Hidden]

I still do not understand. The study says, "22% of our patients developed metastasis in the presence of an undetectable PSA." I don't care how many patients they had. I want to know how many patients that had undetectable PSA had metastasis. Thanks.

[tango65]

Most or all the cancers which progress without expressing PSA do not express enough PSMA either, so the metastases will not be detected by a PSMA PET/CT.

[Hidden in reply to tango65]

See, this is what I am not so sure of. Do you know this for a fact, and if so, what scan is used?

[tango65 in reply to Hidden]

These are some of the articles indicating lower expression of PSMA in small cell/neuroendocrine PC:

ascopubs.org/doi/abs/10.120...

pubmed.ncbi.nlm.nih.gov/304....

I think is common knowledge that NEPC does not express PSA.

[Hidden]

22% of the 46 person subset that represented patients that had developing metastasis with low PSA of under 2. 10 patients. Its rare but it does happen. Sometimes ADT can cause the cancer to change, sometimes it does it in its own. Its a controversial area. Of the 10, 8 of them had small cell carcinoma. I presume that is the same as neuroendocrine. Its an interesting article. Thanks for posting it.

[Tall_Allen]

Three different kinds of PSMA PET scans have been approved for high risk patients as well as recurrent patients.

But you seem to misunderstand the 2007 (pre-PSMA) article you cited. The new PSMA, Choline or Axumin scans would not detect those low PSA-subtypes either. They would show up on FDG PET scans.

[ADTMan in reply to Tall_Allen]

Tall:

Good call. In the 12/23/21 NEJM p. 2494 (which I just read), it states, "Loss of PSMA expression can challenge the success of PSMA-targeted therapy. . . . Thus, combining FDG and PSMA imaging can help identify aggressive lesions with PSMA loss that may preclude Lu-PSMA - 617 therapy. . . ."

I was diagnosed high risk before PSMA Pet was approved. Can I get a PSMA scan now? I am unaware of any institution that will order a PSMA scan without evidence of increased PSA after primary therapy. Which brings up another point now that I think of it -- a PSA avid lesion which was missed with primary therapy would still show up. That is why PSMA scans are ordered after failure of primary therapy.

Anyway, in my defense, I was unaware that metastasis in the absence of PSA would not show up on a PSMA scan. PSA and PSMA are not the same thing. Now it seems that if your physicians do not order a periodic FDG scan - setting aside the PSMA Pet - you might go undiagnosed until you have clinical signs. Good luck trying to get both.

😷

[Tall_Allen in reply to ADTMan]

Low PSA subtypes are very rare.

[dhccpa in reply to Tall_Allen]

What do docs normally do to help those patients?

[Tall_Allen in reply to dhccpa]

Good idea to start with biopsy , IHC and genomics.

[Hidden in reply to Tall_Allen]

Interesting article that suggests a special scan for NE detection.

mdpi.com/1422-0067/22/23/13...

Also thought it was interesting that they suggest most typical adenoC has some NE in it and the degree of the amount suggests the prognosis. This appears to have been performed on mice, though, which I guess means none of us will ever benefit from it

[Tall_Allen in reply to Hidden]

It's a long way off. Biopsy is the bast diagnostic tool.

[Hotrod65 in reply to Hidden]

Believe they call it Adenocarcinoma with SC Neuroendocrine differentiation, it takes intensive pathological testing to properly diagnosis it..standard of care did nothing for me until I qualified for Checkpoint inhibitors PD1 immunotherapy, from Genomic Sequencing of my removed prostate tissue.

[Hidden]

When I was reading Tom Penny’s blog it seemed he had CT scans toward the end that showed his lung cancers. I really don’t know what a CT scan does though. I guess it is xray on steroids

[Tony666]

Please also keep in mind the very real problem of a “false positive”. I had high risk prostate cancer (Gleason 9) and had a psma pet scan as part of a trial and it was avid on 2 ribs. However, it ultimately was not determined to be prostate cancer. This caused me needless anxiety. Psma can be expressed by benign causes as well. I think that’s one reason it’s not offered unless there are other indications of possible metastasis.

[lokibear0803 in reply to Tony666]

How did you later determine it was not cancer?

[Tony666 in reply to lokibear0803]

Good question. I suggested that they biopsy the ribs but they didn’t want to, saying that it would be both difficult and indeterminant. So after I started adt +3 and brought my psa to below 0.02 (part of the trial) they did another psma pet and the cancer in the prostate was no longer psma avid but the ribs showed the same avidity (eg were totally unaffected by the elimination of testosterone). Then they did the same thing 3 months later with the same result. At the same time, they did a different psma pet scan and it didnt pick up anything in the ribs. They concluded that as the adt+3 totally eliminated the avidity in the prostate but had no affect on the ribs avidity and that the different psma pet didn’t correlate, it was likely the ribs avidity was some other reason, most likely trauma or arthritis of some sort.

[lokibear0803 in reply to Tony666]

Thanks Tony666. Just two more things if you don't mind, what is "adt +3" and what were the two different types of PSMA PET scans? At least I think that's what you mean, e.g. you might mean that one of the scans was Ga-68 and the other was DCFPyL? If so, which one did NOT pick up anything in ribs?

[Tony666 in reply to lokibear0803]

Adt+3 is adt (goserelin) + enzalutimide + abiraterone + prednisone. The two psma pet scans were 18FDCFPyL (this was the main scan) and psma pet choline scan (this did not pick up the ribs).

[lokibear0803 in reply to Tony666]

Very interesting...my situation is analogous (somewhat) to yours, and your sequence of events has helped me figure out the next set of questions to ask my MO. So, I thank you.

[Hidden]

This seems to happen a significant % of time. I think doctors would rather radiate first and ask questions later, to be on the safe side. Did they do a biopsy? How did they find out?

[Hotrod65]

I'm scNEPC differenciation from diag. 7 yrs ago..very aggressive disease, for the amount of cancer found in my prostate and regional Mets my PSA should have been thru the roof..but extremely low..it's a badass form of this disease and not many treatment options available.

[Hidden in reply to Hotrod65]

You must have a very good MO. So 100% of your cancer has morphed over to NE and you are in remission? That is amazing

[Hotrod65 in reply to Hidden]

Adenocarcinoma with Neuroendocrine diff...yes from start, Cisplatin /Carboplatin with combo Taxanes did nothing..given 3 months tops..alot of experimental drugs and alot of perseverance has me still in Long Term Clinical Remission NED...done with treatment..was on Pembrolizimab 55 Infusions and just 2 annual maintenance doses going forward..I consider my MO one of the best around when others gave up on me..helps to have a Genitourinary Oncologist and director of Molecular Oncology Research specialization PC..

[j-o-h-n in reply to Hotrod65]

For anyone's information "KEYTRUDA is pembrolizumab". Which has worked for my lung melanoma.

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/29/2021 11:30 PM EDT

[Hotrod65 in reply to j-o-h-n]

Yes, J-o-h-n, is correct, Pembrolizimab is Keytruda a PDL1 checkpoint inhibitor form of Immunotherapy or precision Targeted therapy developed by Merck Pharma and effective for a handful of Cancers, Lung, Colon, Kidney and Malignant Melanomas..some rare cases of Prostate...Myself and a few others..but not FDA approved , usually determined by Genomic testing and clinical trials and experimental use if a candidate?.