What experience has anyone had with the Signatera blood test?

I have high grade muscle invasive bladder cancer initially thought to be stage 2 after a turbt at a local community based hospital. My new doctors strongly advocate the use of Signatera. (I’m now at a major NY city cancer teaching and research hospital ) My initial Signatera result was 18.0 prior to radical cystectomy surgery to and was restaged post radical cystectomy to stage 3 advanced cancer. I went to non dectectable after 4 cycles of gemcitibine and cisplatin. It stayed that way for 11 months and became detectable again with a number of 0.33. A pet scan showed uptake in one concerning uptake in one lymph node and I was put on padcev and keytruda. I am back to non detectable after 2 cycles of the new drug. I should also say that in no time since initial diagnosis in 2023 did a CT scan show that the cancer had spread outside my bladder. The spread wasn’t confirmed until the pathology post radical cystectomy.
So I would have to say that Signatera is giving my doctors early warning that there is a problem and has been a great tool to guide treatment. It was devastating to hear that the cancer came back this year but the early warning , confirmed with a pet scan gave us a heads start on treatment that might have taken months to show on a CT scan.

That's such great news @jaxfl. We've completed three ctDNA draws and all have come back clean. Let's keep the party rolling.

Finally got my results from Natera after three months of waiting. The first samples from Mayo surgery in May 2025 were not useable. They needed samples from my TURBT in late 2024. The good news was the results were negative. Natera’s patient portal sucks. It still shows they are waiting for tissue. It does not show any results. After two months of asking why the portal has not been updated, they gave me a phone number to call. If they would have done that two months ago, I would not have to make a bunch of phone calls to find out the status of my test.

My 8/27 Signatera was negative again fortunately. My 8/28 CT scan showed ground glass, mucus plugging and a few nodules < 4mm. My oncologist and Cancer Commons think this is another IRAE. Likely related to my left side sinusitis symptoms. So this negative Signatera highly likely corroborates this. My 8/27 MRI was clear and even showed the liver iron deposit (likely cause by 2X 1000MG iron IV before and during DDMVAC) resolved as did the adrenal glad atrophy (another IRAE).

Based on additional personal research my hypothesis appears reasonable.

This study indicates ICI response with significant reduction in Northstar Response and low burden to begin with. https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2025.43.16_suppl.e14548

This study used a 120 cut off for clinical relevance of Northstar Response values and it also explicitly states every patient has a methylation baseline. So very low burdens are not clinically interpretable. Which correlates with the emphasis on using Northstar for late stage malignancy and not to use it for MRD/recurrence or early stage malignancy. https://www.nature.com/articles/s41598-025-90013-3

Northstar Response came back at 44. Up 1 from 5/29 43. Which is bizarre. If nivo is ineffective it would go up. If nivo is effective it would be down. The most plausible hypothesis is that this is aberrant but not malignant methylation. The assay was updated and far more sensitive now with a 10 to 400K scale. B2O also includes language not to use it for mrd/recurrence monitoring.

Oh no! Another issue! I'm sure that's frustrating.

Mayo forgot to put in the order for Northstar so they only started processing my sample on 8/5. Now I have to wait until Thursday or Friday this week for the results. Another disappointing Mayo experience. I wonder if it is incompetence or deliberate.

My 2024-1016 TURBT tissue had to be used. I had to coordinate with Baptist to get it to Natera.

I've read on this discussion board a few times that the initial tissue samples have not been good enough and were inadequate for the Natera initial sample test. My situation was exactly the same. The initial tissue sent was from my RC surgery and unable to be used. They requested the turbt tissue taken five months prior to that (at the time of diagnosis) and that tissue was able to be tested. I assumed it had to do with my adjuvant chemotherapy. The surgeon and oncologist agreed the chemo prior to RC had successfully attacked the cancer. I assumed that made sense that the same tissue (if damaged by chemo) would not test well.

I've not had any issues with the Natera tests since then.