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Testing for subtypes and neuroendocrine prostate cancer

Posted by dpfbanks @dpfbanks, May 18 11:07am

I am curious if anyone has experience with testing for neuroendocrine prostate cancer or similar subtypes that may express minimal PSA. I have read about 3 blood tests to detect (Neuroendocrine Monitoring panel, ChronigenA, and Neuron specific enolase) in addition to testing biopsy tissue.

We have not had any of those tests nor was the lung Mets biopsy tested further than ‘adenocarcinoma from the prostate’. Two different liquid biopsies (not yet discussed with the team) showed low tumor burden, < 0.1 circulating cells and 1 mutation (NF-1 a tumor suppressor gene).

Our treatment is aggressive assuming a potential NEPCa, but I am thinking to ask for testing so we aren’t getting this heavy treatment based on assumption due to the one fact of low PSA (0.34) with lung only metastasis.

Yes, we will be asking our team further, but wondering about any knowledge or experience here. Thank you - such a helpful and supportive forum.

Interested in more discussions like this? Go to the Prostate Cancer Support Group.

jeff Marchi | @jeffmarc | May 18 12:02pm

I have heard that the FDG scan will detect neuroendocrine cancer, here is some information about that.

From NIH Frontiersin and LWW

Yes, an FDG scan (FDG-PET/CT) can detect neuroendocrine prostate cancer (NEPC), especially in cases where the disease is aggressive or advanced.
• FDG-PET has demonstrated clinical utility in detecting metastatic disease in patients with NEPC and can also be used to monitor treatment response and tumor viability.
• NEPC and aggressive prostate cancers often show increased glucose metabolism, making them more visible on FDG scans, unlike typical prostate adenocarcinoma where FDG-PET is less sensitive.
• In some cases, NEPC lesions may be FDG-avid even when PSMA-based scans are negative, so FDG-PET can be particularly valuable in these settings.
• However, some low-grade neuroendocrine tumors may not be intensely FDG-avid and could be better visualized with other tracers like 68Ga-DOTATATE

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1 reply
dpfbanks | @dpfbanks | May 21 2:16am
In reply to @jeffmarc "I have heard that the FDG scan will detect neuroendocrine cancer, here is some information about..." + (show)
@jeffmarc

I have heard that the FDG scan will detect neuroendocrine cancer, here is some information about that.

From NIH Frontiersin and LWW

Yes, an FDG scan (FDG-PET/CT) can detect neuroendocrine prostate cancer (NEPC), especially in cases where the disease is aggressive or advanced.
• FDG-PET has demonstrated clinical utility in detecting metastatic disease in patients with NEPC and can also be used to monitor treatment response and tumor viability.
• NEPC and aggressive prostate cancers often show increased glucose metabolism, making them more visible on FDG scans, unlike typical prostate adenocarcinoma where FDG-PET is less sensitive.
• In some cases, NEPC lesions may be FDG-avid even when PSMA-based scans are negative, so FDG-PET can be particularly valuable in these settings.
• However, some low-grade neuroendocrine tumors may not be intensely FDG-avid and could be better visualized with other tracers like 68Ga-DOTATATE

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Thank you for this - have seen this fog mentioned and will research. Our first PET was a 68Ga, supposed to have been one of 3 machines in the world. The 2nd was psma pet/ct at Mayo, which I believe is next month also. We have not had the choline eithe, which I understand can show things that don’t light on others or are obscured by the PSMA uptake say in the bladder.

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1 reply
jeff Marchi | @jeffmarc | May 21 10:26am
In reply to @dpfbanks "Thank you for this - have seen this fog mentioned and will research. Our first PET..." + (show)
@dpfbanks

Thank you for this - have seen this fog mentioned and will research. Our first PET was a 68Ga, supposed to have been one of 3 machines in the world. The 2nd was psma pet/ct at Mayo, which I believe is next month also. We have not had the choline eithe, which I understand can show things that don’t light on others or are obscured by the PSMA uptake say in the bladder.

Jump to this post

The choline Scan is not usually used for neuroendocrine detection.

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dpfbanks | @dpfbanks | May 21 12:35pm

Thanks, Jeff. If I understand correctly, the choline catches other spots that the psma uptake might obscure. I am reading about the FDG-PET so thanks for that. I have little knowledge of it and it’s not been mentioned - that’s what we are having a hard time swallowing: the lack of desire to confirm the subtype to be sure it matches the treatment. The new NEMO panel developed at Dana Farber is exciting and when it available should help in cases like ours .

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1 reply
jeff Marchi | @jeffmarc | May 21 2:04pm
In reply to @dpfbanks "Thanks, Jeff. If I understand correctly, the choline catches other spots that the psma uptake might..." + (show)
@dpfbanks

Thanks, Jeff. If I understand correctly, the choline catches other spots that the psma uptake might obscure. I am reading about the FDG-PET so thanks for that. I have little knowledge of it and it’s not been mentioned - that’s what we are having a hard time swallowing: the lack of desire to confirm the subtype to be sure it matches the treatment. The new NEMO panel developed at Dana Farber is exciting and when it available should help in cases like ours .

Jump to this post

Once somebody has been diagnosed with Neuroendocrine prostate cancer there is really not much that can be done. Getting a scan to see where it is it is not really going to change the treatment plan.

There was one DLL3 study (UCSF Aggarwal) that was a possible trial for prostate cancer patients, but they changed it about a year ago so that only breast cancer patients are involved. I’m not heard that they changed it back but there are many studies in the works, see below.

The two people I know who have had neuroendocrine cancer have died within a year. It is one thing I worry about since I’ve been on these drugs for so many years and that has been found to be one of the factors to cause it. Have heard of Neuroendocrine patients living a couple of years maybe more.

From: MSKCC TargetDonc onclive ascopubs
There are several ongoing clinical studies targeting DLL3 in neuroendocrine prostate cancer (NEPC):
• Memorial Sloan Kettering Cancer Center (MSK) is opening a clinical trial testing a radioactive ligand that targets DLL3 in people with metastatic NEPC. Patients will first be screened for DLL3 expression and, if eligible, will receive the targeted therapy.
• The SKYBRIDGE trial (NCT05652686) is a phase 1/2 study evaluating peluntamig (PT217), which targets DLL3 and CD47, in patients with DLL3-expressing neuroendocrine carcinomas, including NEPC.
• A phase 1b study of tarlatamab, a DLL3-targeted bispecific T-cell engager, is ongoing in patients with metastatic NEPC, showing manageable safety and encouraging anti-tumor activity in DLL3-positive cases (NCT04702737).
• Other agents like HPN328, another DLL3-targeted T-cell engager, are also being tested in neuroendocrine prostate cancer.
These studies reflect a strong research focus on DLL3 as a therapeutic target for NEPC.

REPLY
1 reply
dpfbanks | @dpfbanks | May 22 6:45am
In reply to @jeffmarc "Once somebody has been diagnosed with Neuroendocrine prostate cancer there is really not much that can..." + (show)
@jeffmarc

Once somebody has been diagnosed with Neuroendocrine prostate cancer there is really not much that can be done. Getting a scan to see where it is it is not really going to change the treatment plan.

There was one DLL3 study (UCSF Aggarwal) that was a possible trial for prostate cancer patients, but they changed it about a year ago so that only breast cancer patients are involved. I’m not heard that they changed it back but there are many studies in the works, see below.

The two people I know who have had neuroendocrine cancer have died within a year. It is one thing I worry about since I’ve been on these drugs for so many years and that has been found to be one of the factors to cause it. Have heard of Neuroendocrine patients living a couple of years maybe more.

From: MSKCC TargetDonc onclive ascopubs
There are several ongoing clinical studies targeting DLL3 in neuroendocrine prostate cancer (NEPC):
• Memorial Sloan Kettering Cancer Center (MSK) is opening a clinical trial testing a radioactive ligand that targets DLL3 in people with metastatic NEPC. Patients will first be screened for DLL3 expression and, if eligible, will receive the targeted therapy.
• The SKYBRIDGE trial (NCT05652686) is a phase 1/2 study evaluating peluntamig (PT217), which targets DLL3 and CD47, in patients with DLL3-expressing neuroendocrine carcinomas, including NEPC.
• A phase 1b study of tarlatamab, a DLL3-targeted bispecific T-cell engager, is ongoing in patients with metastatic NEPC, showing manageable safety and encouraging anti-tumor activity in DLL3-positive cases (NCT04702737).
• Other agents like HPN328, another DLL3-targeted T-cell engager, are also being tested in neuroendocrine prostate cancer.
These studies reflect a strong research focus on DLL3 as a therapeutic target for NEPC.

Jump to this post

How tragic. My current exploration is more about finding NEPC via testing of biopsy or blood studies. We already know where the clusters are located (lungs). We want to know more about the makeup of those clusters to match the best treatment. If we are treating aggressively based on the assumption that low PSA + lung only metastasis means it is potentially a NEPC, we believe said testing is essential, if available. It appears that the new NEMO panel coming out of DanaFarber will do just that— when it becomes clinically available. If we are dealing with hormone acinar ademnocarcinoma only, perhaps we can dial back to triple therapy without the need for carboplatin - this is the intent of this scrutiny. And if NEPC has the outlook you describe, we would want to know that, even with its dire outcome.

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