@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.