What Does Tumor-Informed ctDNA Mean?

This page is for people whose blood test report mentions a tumor-informed ctDNA test. It explains how these tests are built, what the results can and cannot tell you, and what to ask your care team.

Circulating tumor DNA, or ctDNA, is DNA that a tumor sheds into the bloodstream. A blood draw can pick it up. The hard part is telling it apart from normal DNA, which is in the same tube in far larger amounts.

There are two ways to solve that, and the label on your report tells you which was used.

A tumor-informed test starts with your tumor. The lab sequences tissue from your surgery or biopsy. It finds mutations unique to that tumor. Then it builds a blood test that hunts only for those mutations. The panel is built for one person's tumor.

A tumor-naive (tumor-agnostic) test skips the tissue step and uses a fixed panel instead.

Signatera is one example. A review in Biomarker Research (hosted on PubMed Central) describes it this way. The lab uses whole exome sequencing on the tumor tissue. That reads the protein-coding parts of the genome. From that read, it selects 16 somatic variants. Somatic means the tumor acquired them. They were not inherited.

Those 16 targets become your personal blood assay. The reported detection threshold is 0.01 percent variant allele frequency. A sample is called positive when at least 2 of the tracked variants show up in the blood.

The same review lists other tumor-informed assays, including MRDetect, FoundationOne Tracker and Safe-SeqS. It lists Guardant Reveal as a tumor-agnostic test that reads more than 1,000 genomic regions.

A ctDNA result only means something at the right moment. The review reports these figures for two tests:

• Signatera, about 30 days after surgery: 88 percent sensitivity, 98 percent specificity
• Safe-SeqS: 48 percent sensitivity

Sensitivity is the share of people with leftover cancer that the test correctly flags. Specificity is the share of cancer-free people it correctly clears. For Signatera, specificity is higher than sensitivity. A negative result is softer news than it sounds. Ask your team which timing and figures apply to your test.

NCI's Cancer Currents blog describes the BESPOKE CRC study of people with colorectal cancer. It began in 2020 and enrolled nearly 1,800 people. Results from 623 of them were presented in 2024. Natera, Inc. funded the study and provided the ctDNA test.

Testing took place 1 month after surgery, every 3 months for one year, and then twice a year.

Of the 623 participants, 381 received chemotherapy after surgery. Among those, 85 had a positive ctDNA result and 296 had a negative one.

The gap in outcomes was wide. People with positive ctDNA who got chemotherapy had a median recurrence-free survival of almost 18 months. People with positive ctDNA who did not get chemotherapy had about 7 months. Now the negative group. More than 90 percent went a median of over 2 years with no recurrence. That held whether or not they had chemotherapy.

In the follow-up, 14 people went from a negative to a positive ctDNA result.

ctDNA can turn positive before a scan shows a return of cancer. The review reports that serial ctDNA testing detected recurrence ahead of imaging, with a mean lead time of 5.01 months. Knowing earlier is not automatically the same as living longer. That is the question current trials are built to answer.

In BESPOKE, 101 people had their cancer come back. Of those, 40 had oligometastatic disease. That means a small number of spots. Whether finding them earlier helps people live longer has not been shown by this study.

A test with 88 percent sensitivity can still miss some people who have leftover cancer.

The background risk also stays. NCI notes that about a quarter of people with stage II or III colorectal cancer are not cured, even with chemotherapy after surgery. A negative ctDNA test does not mean zero risk. Ask your oncologist whether it changes your scan schedule.

In November 2024 the FDA issued guidance titled "Use of Circulating Tumor Deoxyribonucleic Acid for Early-Stage Solid Tumor Drug Development." It addresses ctDNA as a biomarker in cancer clinical trials of early-stage solid tumors. It covers assay considerations for molecular residual disease, and standardization of ctDNA assays across labs.

The document is about using ctDNA in drug development. Ask your team how it applies to your own care.

• Is my test tumor-informed or tumor-naive, and which product is it?
• How many days after surgery was the blood drawn, and does that match the validated window?
• If the result is positive, what specifically changes? More chemotherapy, different chemotherapy, or earlier imaging?
• If the result is negative, does my scan schedule change at all?
• Is my insurance covering this, and what is my share if it does not?
• Is there a clinical trial where this result would guide treatment under a protocol?

https://www.cancer.gov/news-events/cancer-currents-blog/2024/colorectal-cancer-ctdna-may-guide-adjuvant-therapy

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-circulating-tumor-deoxyribonucleic-acid-early-stage-solid-tumor-drug-development-guidance

https://pmc.ncbi.nlm.nih.gov/articles/PMC12186373/ (Ma et al., Biomarker Research, 2025)