Signatera CT DNA Test: What numbers have you seen on your tests?

This is all really interesting and helpful to read. I asked my mom’s oncologist about Signatera testing and he said they haven’t adopted it for use yet due to unclear benefit (Cleveland Clinic). My mom has always had lower Ca19-9 levels anyway (219 at diagnosis, was always 3-6 for 4 years after distal surgery, just had a recurrence limited to the ovaries and it went up to 12, waiting to see what it is now that her ovaries were removed) so it sounds like ctDNA may not be accurate for her anyway since Ca19-9 has consistently been low?

> "it sounds like ctDNA may not be accurate for her anyway since Ca19-9 has consistently been low?"

That sounds logical and seems to fit my (and Amy's mom's) pattern, but I have no data or qualifications to generalize that to other patients or cases.

> "they haven’t adopted it for use yet due to unclear benefit"

I've had it rejected by insurance as "medically unnecessary" several times, but my hospital has always found some way to get it reimbursed.

Is your signatera able to detect all 16 assays? I've just started with this monitoring, and only got 8 assays from my original tumor biopsy. So its not ideal. Also, ca19 has always been pretty low. 174 and diagnosis, 450 at peak on ineffective chemo, then under 35 since December 2022. Seing an upward trend over the last 1.5 years from 11 to 27.

@ashley2235 -- Good question, and the answer is "I don't know." How does one find out? I didn't see (or don't remember) any references to that on my reports.

It was discussed under limitations on my first report. Then I had a call with a signatera genetic counselor and she explained how many assays they were able to collect. Because I was curious as to what it meant.

I don't have copies of my first few reports. I will see if they are buried in my patient portal, or call Natera and see if they can explain. I don't see anything on my later reports about how many assays they were able to detect. I do see a note I hadn't noticed before:

"Testing cannot be performed in patients who are pregnant, have a history of bone marrow transplant, or history of blood transfusion within three months."

The transfusion limitation may invalidate some of my results. 🙁

My husband had this test done just once... pre-diagnosis ... and his oncologist doesn't seem to see the need to repeat. Maybe he is relying more on the CA19-9 numbers which have gone from over 39000 to 325 in the past 15 months.

@sheridanb -- Are you thinking of a different ctDNA test like the Guardant 360 or a germline test like Invitae? The Signatera test requires tumor tissue, which your husband would not have had pre-diagnosis. There is definitely no need to repeat a germline test, unless the first one was limited in the number of mutations it could check for and you now want to check for others.

Tissue testing or repeats of Guardant might reveal new somatic mutations, but those don't generally happen at a rate that warrants frequent repeat testing. I have zero medical training, but if I experienced a rapid progression of disease while on a particular therapy, I might ask for another Guardant test to see if progression is related to a new mutation.

Signatera's strength, in general, is detecting MRD (Microscopic Residual Disease) -- where DNA shed by the cancer is circulating in the blood, but tumors are too small to detect on imaging. This gives doctors evidence that disease is still present and needs to be treated. Since it's a quantitative test, the resulting number does give a good idea if treatment is working or not. Your husband's CA19-9 numbers strongly suggest his therapy is working, and I would expect his scans over the last 15 months to support that (either with tumor shrinkage or findings of "stable disease"). If the CA19-9 numbers level off and imaging can't determine whether the "masses" are live vs dead tumor tissue, then Signatera might be a good option. Like with any test, knowing a baseline result is helpful so you'll have something to compare future results against.

@sheridanb -- Are you thinking of a different ctDNA test like the Guardant 360 or a germline test like Invitae? The Signatera test requires tumor tissue, which your husband would not have had pre-diagnosis. There is definitely no need to repeat a germline test, unless the first one was limited in the number of mutations it could check for and you now want to check for others.

Tissue testing or repeats of Guardant might reveal new somatic mutations, but those don't generally happen at a rate that warrants frequent repeat testing. I have zero medical training, but if I experienced a rapid progression of disease while on a particular therapy, I might ask for another Guardant test to see if progression is related to a new mutation.

Signatera's strength, in general, is detecting MRD (Microscopic Residual Disease) -- where DNA shed by the cancer is circulating in the blood, but tumors are too small to detect on imaging. This gives doctors evidence that disease is still present and needs to be treated. Since it's a quantitative test, the resulting number does give a good idea if treatment is working or not. Your husband's CA19-9 numbers strongly suggest his therapy is working, and I would expect his scans over the last 15 months to support that (either with tumor shrinkage or findings of "stable disease"). If the CA19-9 numbers level off and imaging can't determine whether the "masses" are live vs dead tumor tissue, then Signatera might be a good option. Like with any test, knowing a baseline result is helpful so you'll have something to compare future results against.