Neuroendocrine Prostate Cancer

[Tall_Allen]

I added some new info on somatostatin detection and DLL3:

pcnrv.blogspot.com/2016/12/...

[Ahk1]

Thank you, TA. I will read it.

[SPEEDYX]

Excellent study...I was wondering why my MO at mskcc test for it....it was slightly elevated but believe it was related to acid inhibitor I was taking ...he was not concern....Thank TA

[SPEEDYX in reply to SPEEDYX]

The Chromogranin A test

[Tall_Allen in reply to SPEEDYX]

Chromogranin A is not a test for NEPC, in spite of what you may have read on this site.

[SPEEDYX in reply to Tall_Allen]

Thanks for info!!!

[Dalipup]

Thanks! These decisions are mind boggling! Never thought I'd be this proficient at reading trial protocols!

[cesanon]

"A similar radiopharmaceutical using Lu-177-DOTATATE (called Lutathera) has been FDA-approved for small cell cancer affecting the digestive tract. DOTATOC (and also DOTATEC and DOTATATE) binds to somatostatin receptors on the small cell digestive tract cancer surface, where it is highly expressed. It is rarely expressed in small cell prostate cancer, but there have been some isolated case reports like this one or small trials like this one."

Do I take this to say that this treatment may work, but not very often because somatostatin "is rarely expressed in small cell prostate cancer,"

Did I understand that properly?

Seems like there really is not much available to treat small cell prostate cancer. Even the good stuff is not that effective.

[Tall_Allen in reply to cesanon]

It is found heavily expressed in NE tumors in the digestive tract, but sometimes in NEPC (as they found at Emory). If you have NEPC, it's worth checking for.

[dvcarola2]

Thank you for this informative post TA. Btw, my husband had PDL-1 test a few months ago from the initial biopsy result that is kept in the hospital in 2018. The result came up with <1%. So, our oncologist said that immunotherapy like keytruda is not an option. Does that also mean that my husband is negative for small cell pca? How about for neuroendocrine pca?

[Tall_Allen in reply to dvcarola2]

No, it tells you nothing about NEPC.

[podsart]

I know you tried to fix my connection to this newsletter a while ago , but still not getting it.

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

JUST FOR YOU:

Sunday, December 18, 2016

Small Cell Prostate Cancer Clinical Trials

Small Cell Prostate Cancer (SCPC), and more generally Neuroendocrine Prostate Cancer (NEPC), are thankfully rare types of prostate cancers. They are not responsive to hormone therapy, to taxanes (Taxotere or Jevtana), or to radiation. They are difficult to detect and monitor with the kinds of imaging used to detect prostate adenocarcinoma (mpMRI, bone scans, PSMA PET scans), but may show up with FDG PET (see this link). They do not put out PSA, PAP or bone alkaline phosphatase. Special biochemical tests or biopsies for chromogranin A, neuron-specific enolase (NSE), synaptophysin, DLL-3, CD56, and other biomarkers are required. Complicating matters, it often appears at a "mixed type" (17% of heavily treated patients with mCRPC had neuroendocrine differentiation in this study) that may be partially responsive to familiar therapies. There are some studies that indicate that they may appear spontaneously in later stages of normal prostate cancer development.

Chemotherapy

Because of the "mixed type," chemo often includes a taxane. More often, a platin is mixed in a cocktail with another chemo agent, like etoposide. A couple of case reports from Japan (see this link and this one) reported some success with a platin combined with irinotecan.

Nuclear Medicine/ Somatostatin

Perhaps the most promising treatment to date has been tried by the nuclear medicine department at the University of Heidelberg. I suggest that anyone who is interested email or call (they all speak English) [e-mail] Phone: [phone]. With the euro now at close to parity with the dollar, this medical tourism is an especially attractive option:

213Bi-DOTATOC shows efficacy in targeting neuroendocrine tumors

A similar radiopharmaceutical using Lu-177-DOTATATE (called Lutathera) has been FDA-approved for small cell cancer affecting the digestive tract. DOTATOC (and also DOTATEC and DOTATATE) binds to somatostatin receptors on the small cell digestive tract cancer surface, where it is highly expressed. It is rarely expressed in small cell prostate cancer, but there have been some isolated case reports like this one or small trials like this one. This means that treatment with a somatostatin analog (octreotide, lanreotide, or pasireotide) may be somewhat effective even without the radioactive emitter attached to it. These drugs are available now in the US, are not toxic, and your doctor can prescribe them without a clinical trial. there is a clinical trial of it in London for any solid tumor:

clinicaltrials.gov/ct2/show...

These clinical trials include somatostatins:

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

While the presence of somatostatin receptors in the tumor can be determined by pathological analysis (immunohistochemical (IHC) staining for SSTR2), there is an FDA-approved PET scan that uses Ga-68-DOTATATE that can detect it without a biopsy. It is used to detect neuroendocrine tumors that are often non-prostatic. Researchers at Emory found that Ga-68-DOTATATE uptake is higher even in neuroendocrine tumors of prostatic origin, which suggests that somatostatin-based therapy may be beneficial. (One patient who was positive for a BRCA2 mutation but negative for NEPC had high uptake as well.)

DLL3

DLL3 is a protein that is expressed on the surface of neuroendocrine cells regardless of the cancer of origin, and has been identified in two-thirds of neuroendocrine prostate cancer (NEPC) cells. An antibody linked to a chemotherapy, called Rova-T, against DLL3 has been developed and has shown some promise against NEPC in a preclinical study. Unfortunately, AbbVie discontinued R&D after it failed to meet goals for small cell lung cancer (SCLC). A Phase 2 trial that included NEPC was discontinued.

There are two other DLL3-targeted immunotherapies in trials for SCLC that may turn out to be beneficial for NEPC as well. AMG757 is a bispecific T-cell engager (BiTE) that targets DLL3 and also promotes T cells to attack those cells exhibiting it. AMG119 is a CAR-T therapy that targets DLL-3. CAR-T involves treating one's own T-cells by sensitizing them to DLL3. Both of these create a T-cell and a cytokine response in environments that otherwise have low immune cell activity. That response may kill bystander cells, and through a phenomenon called "antigen spreading," may be able to kill other cancer cells that do not exhibit DLL3. (BiTE and CAR-T therapies that target PSMA are in clinical trials noted at end of this article)

The Wang Lab at Duke has specific expertise in morphological analysis of NEPC and IHC staining for DLL3. It may be a good idea to get a second opinion from them.

Checkpoint blockade

Another recent discovery that gives a lot of hope is that PD-L1 is highly expressed in SCPC. This opens the door to immunotherapies that target the PD-1/PD-L1 pathway, like Keytruda.

PD-L1 expression in small cell neuroendocrine carcinomas

Several clinical trials use checkpoint blockade:

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

Posted by Allen at 3:58 PM

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Labels: BiTE, CAR-T, chemo, clinical trial, immunotherapy, neuroendocrine, nuclear medicine, small cell, somatostatin

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About the Author

Allen Edel is a patient advocate for men with prostate cancer, and has been published in the Journal of Urology. He writes a regular column for the New Prostate Cancer Infolink, and works with support groups.

Read Allen Edel's novels:

Thaw's Hammer (print)

Thaw's Hammer (ebook)

Joan of Quebec (print)

Joan of Quebec (ebook)

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Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 02/15/2020 12:38 PM EST

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

thanks

[Tall_Allen in reply to podsart]

I didn't yet look into it, sorry- maybe after I do my taxes.

[podsart]

thanks

doing my taxes now as well ..

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

Remember to cheat.......

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 02/15/2010 7:27 PM EST

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

You have to take up the tax before you can pick up the carpet

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

Not if you sweep your winnings under......

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 02/16/2010 11:41 AM EST

[Bird8]

Thank you TA! This information is timely considering Mike’s recent NEPC diagnosis. We have an appt set up with Beltran on April 1st, no joke intended. I will keep the group posted on her thoughts.