Genetic testing recommendations - Advanced Prostate...

Advanced Prostate Cancer

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Genetic testing recommendations

Heykm01 profile image
9 Replies

Just diagnosed with metastatic prostate cancer (M1B) and have started ADT: lupron + darolutamide (more details in profile).

Looking for recommendations to insure I have the best genetic information available. Tumor was submitted for Decipher testing which came back as low risk (0.24).

Submitted blood sample last week for genetic testing.

Appreciate any recommendations to insure most complete information out of this effort. Comments on differences between somatic vs germline. Have read / seen references to PTEN, BRCA etc mutations. I don't know if those are measured in the tumor or can be done from a blood sample.

Have also seen literature indications that these mutations can change over time (it's a mutation, after all).

Have found this forum to be very useful. Thanks to all commentators.

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Heykm01
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Tall_Allen profile image
Tall_Allen

With 3 metastases on a bone scan, I hope you are also having prostate radiation:

prostatecancer.news/2018/09...

Your blood test may have been germline (inherited) or a test for tumor DNA in your blood.

If you want to test tumor DNA, you can get a biopsy of tumor tissue. A biopsy can tell you more than just about the DNA (which is usually not something that is treatable). Mutations do change over time, but slowly at first.

Heykm01 profile image
Heykm01 in reply to Tall_Allen

Thank you Tall_Allen. Radiation is planned for Dec. Because I was G6, 1/11 cores at 5%, MO thinks scans could still be wrong. Says 3 months scan after ADT will confirm and then we'll do radiation.

You also answered another q I had - whether I'd be considered 'oligometastatic'. By bone scan yes, but not by PET PSMA.

Tall_Allen profile image
Tall_Allen in reply to Heykm01

Only bone scan/CT counts.

tango65 profile image
tango65

Perhaps there is still enough material in the biopsies to do a Foundation One genetic study of the cancer.

assets.ctfassets.net/w98cd4....

Heykm01 profile image
Heykm01 in reply to tango65

Thank you tango65. It appears from the literature PC not much influenced by genetic testing, but seems like its coming. Assuming I have some years on this journey, want to 'be ready'. And there's not much advice on this topic.

tango65 profile image
tango65 in reply to Heykm01

I used the prostatectomy piece and got a Foundation One test which identified a mutation, PTEN loss and nothing else. My genome does not have PTEN loss.

I know the mets have this mutation, but so far we have not been able to biopsy any of them yet. PTEN loss is a frequent mutation in cancers and facilitates the cell division. I believe it is one of the reasons my cancer always has a very shot PSADT.

It is important to get the genome and the histology of the mets, they may indicate particular therapies, such olaparib, rucaparib, keytruda, chemo with platinum compounds etc. and many others in clinical trials.

bluedmnd profile image
bluedmnd

I hope you get a Foundationone sequencing to determine whether you’re a candidate for targeted therapy! Tall_Allen has explained the Germaine vs tumor mutation well

Cooolone profile image
Cooolone

The real question is what are you looking for? Is there family history with a disease? Or searching just for the search sake?

Even "IF" genetic defect is found, there are few actionable markers with approved drugs. And even those drugs have limited results and usually only for a time. There are no miracle fixes that exist with regard to the use of genetics. What are there... A few dozen different (PCa) cell lines that are studied? And genetics have identified hundreds (500+) of defects, etc, associated with PCa as well. But there's so little really understood as to causation, effect, mechanisms and interactions amongst genes, etc. We have only just dipped out toe into this pool!

That said, there's a few studies currently under way that are beginning to track patient genetic signatures and the respective therapies they've received to identify which patients may have better results from therapies based upon their profiles... But genetics is a very complicated subject, it's not always that simple.

You may want to inquire if your Oncology facility is involved with any trials in that regard though, ie, having your tumor tissue tested... You get the results and they get to track you ;)

I did it, and qualified for a trial, and have had multiple tests performed, on tissue post RP, and once it metastasized. It revealed nothing with RP tissue, and the opposite with metastatic tissue that had shown 11 anomalies. My main reason to do it was a family history of cancer, multiple cancers... Anyways...

Even if a defect, deletion, error is identified, AND there is a drug for it, usually approval of its use is for when a patient has already failed multiple treatments and or, has progressed to resistance (castrate)! Therefore, more advanced patients, not newly diagnosed, etc. A major conundrum!

So... It's hard to do the testing early, and have your nose pressed against a window, looking in at something you might be able to try later, but not now, that might work (maybe) and if then, work only for a time, because your test now shows you have something that's been identified as being associated with PCa.

I only say that because genetics are currently, both a blessing, and a curse! Lol

Good Luck and Best Regards

Heykm01 profile image
Heykm01 in reply to Cooolone

Thanks for your detailed response Cooolone. I've read enough to understand that use of genetics / biomarkers for PC or mPC treatment hasn't yet found much traction. It seems to be well recognized that this is a shortcoming.

I've just started my journey here, but am assuming that it will be a multiple (hopefully many) year one. And during that time the use of genetic directed therapies will develop into wider use and effectiveness. So my objective here is to have a baseline, and to hopefully have some areas to follow. There is some family history, and I have two sons, so that's another motivation.

It's also clear as you point out that the therapies all start out with testing on CR patients. And by that point OS progress gets measured in months . . . . With my ADT (lupron + darolutamide) I'm hoping to push out CR for many years.

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