@mse , There is a *slight* chance your liver tumors are independent of the colon cancer you had removed. I say this only because the Signatera test specifically looks for ctDNA cells that match those which came from your original colon tumor. If the liver tumors are independent, then their DNA would not match the older colon tumor as a "common ancestor."

In my case, Signatera was also negative (0.00 mean tumor molecules per mL of blood) at the same time my CA19-9 was 77 and MRI showed recurrent pancreas tumor at 1.3 cm. It wasn't until CA19-9 reached 279 and MRI measured the tumor at 2 cm before Signatera registered a positive ctDNA detection (0.14 MTM/mL). I was about to have the chemo port removed from my chest before this shocker came along.

My Signatera results since then have mostly been 0.00 since treatment began, with a few small deviations (0.06 and 0.04) from zero. In general, the non-zero results seem to correlate with higher CA19-9 readings, but I can't get all my providers to perform consistent enough CA19-9 and Signatera testing to truly compare them.

My understanding is that if Signatera is negative (0.00), you MIGHT have cancer; if Signatera is positive (> 0.00) you DEFINITELY have cancer DNA that matches your original tumor (from which the Signatera test was built) floating in your bloodstream. I think CA19-9 is more sensitive but less specific than Signatera, at least for solid tumors like PDAC.

Because CA19-9 is less specific (and subject to elevation or suppression from other causes), it can't be a sole determinant of cancer status or treatment effectiveness. However, if you have a long CA19-9 history and good measurement baseline over time and changes with disease status, it seems OK to give it more weight. For me, watching CA19-9 is like listening to quiet passages of music via headphones, whereas Signatera is more like listening to louder passages through a big set of speakers. The relatively low cost and availability of CA19-9 testing, coupled with my personal experience, have led me to be a huge advocate for it. (Reminder/Disclaimer: I have zero medical training.)