Signatera test results report whether tumor DNA was detected in your blood, displayed as either positive or negative. If your result includes a quantitative value, you’ll also see a number reported in MTM/mL (mean tumor molecules per milliliter), which reflects how much tumor DNA is circulating. Understanding both pieces, the binary result and the trend over time, gives you the clearest picture of what your results mean.
Positive vs. Negative Results
The core of your Signatera report is straightforward: positive means tumor DNA was found in your blood, and negative means it was not detected. But what that means for you depends on where you are in treatment.
If you have early-stage cancer and have already had surgery, a positive result signals a higher risk that your cancer could return. It doesn’t mean cancer has definitively come back, but it indicates that residual tumor cells are likely still present somewhere in your body, even if imaging scans look clean. A negative result means you’re more likely to remain cancer-free. In a study of 130 patients with stage I to III colorectal cancer, a positive Signatera result after treatment corresponded to a more than 40-fold increase in the likelihood of recurrence compared to a negative result.
If you’re being treated for advanced cancer, a positive result confirms that measurable disease is still present. In this setting, the more important information is often the trend: whether your levels are rising, falling, or clearing entirely.
What the MTM/mL Number Means
Beyond the positive or negative call, your report may include a value expressed as MTM/mL. This metric estimates the concentration of tumor-derived DNA fragments in your blood, factoring in both the proportion of tumor DNA and the total amount of cell-free DNA circulating in your plasma.
A single MTM/mL number on its own has limited usefulness. Its real value comes from tracking how that number changes across multiple blood draws. A declining MTM/mL over successive tests generally signals that treatment is working and tumor burden is shrinking. A rising value suggests the opposite: the tumor may be growing or spreading. Research has shown that changes in MTM/mL correspond closely with what imaging eventually reveals, sometimes providing that information weeks to months earlier.
There is no universal “good” or “bad” threshold for MTM/mL. Two patients with the same number could have very different situations depending on their cancer type, treatment, and prior readings. What matters most is the direction of the trend line across your serial results.
How Signatera Tracks Treatment Response
For patients receiving immunotherapy or other systemic treatments, serial Signatera testing can reveal whether treatment is working before a scan confirms it. In one study of 94 patients with various solid tumors, patients whose tumor DNA levels increased after six weeks of immunotherapy had only a 7.5% chance of remaining progression-free at six months. Patients whose levels decreased at the same time point had a 54.5% chance.
Complete clearance of tumor DNA from the blood is an especially strong signal. In that same study, patients who achieved undetectable ctDNA at any point during treatment had 100% overall survival over a median follow-up of more than two years. This suggests that if your results shift from positive to negative during treatment, the response is likely durable.
Signatera can also help distinguish between true cancer progression and pseudoprogression, a phenomenon where tumors appear to grow on imaging scans but are actually responding to immunotherapy. If your scan looks concerning but your tumor DNA levels are dropping, your oncologist may interpret that as a sign the treatment is actually working.
How Early Signatera Can Detect Recurrence
One of the key advantages of this test is lead time: the gap between when tumor DNA appears in your blood and when a recurrence would show up on a CT or MRI. In a breast cancer study tracking patients after surgery, Signatera detected metastatic relapse a median of 10.5 months before imaging confirmed it. In some cases, that lead time stretched to more than three years.
The test can detect tumor DNA at extremely low concentrations, with over 98% analytical sensitivity at levels as low as 0.01% to 0.02% of circulating DNA. In colorectal cancer patients monitored every three months for up to three years, the test predicted 14 of 16 clinical relapses (87.5%). This high sensitivity is why many oncologists use Signatera as a surveillance tool between scans.
When a Negative Result Might Be Misleading
A negative Signatera result is reassuring, but it isn’t a guarantee. Certain biological factors can cause tumor DNA to be undetectable even when cancer is present. The amount of tumor DNA that reaches your bloodstream depends on the tumor’s size, location, blood supply, and physical characteristics.
Tumors in the peritoneal cavity (the lining of the abdomen) are a well-known blind spot. The peritoneum acts as a barrier between the tumor and the bloodstream, similar to how the blood-brain barrier limits what crosses into brain tissue. In patients with gastrointestinal cancers that had spread to the peritoneum, Signatera detected tumor DNA in only 53% of cases. Tumors with mucinous features, where the cancer produces thick mucus, are particularly prone to false negatives because the mucin physically blocks DNA from entering circulation.
Tumors with poor blood supply, small tumor burden, or locations that are anatomically isolated from major blood vessels can also shed less DNA into the bloodstream. If your oncologist suspects recurrence based on symptoms or imaging but your Signatera result is negative, these biological limitations may be the reason.
Reading Your Results Over Time
Signatera is designed as a serial test, meaning individual results are most informative when viewed as part of a sequence. A typical surveillance schedule involves blood draws every few months, timed to coincide with your regular follow-up visits or treatment cycles. Each new data point adds to the trend.
Here’s what the common patterns look like in practice:
- Consistently negative after surgery: Low risk of recurrence. This is the pattern you want to see during surveillance.
- Positive shortly after surgery, then clearing to negative: Suggests that any residual disease was eliminated, either by your immune system or by adjuvant treatment.
- Negative turning positive during surveillance: An early warning of possible recurrence, often months before it would appear on imaging. Your oncologist will likely order scans or adjust your monitoring schedule.
- Declining MTM/mL during treatment: Treatment is likely working. The steeper and more sustained the decline, the better.
- Rising MTM/mL during treatment: The current therapy may not be controlling the disease. This pattern often prompts a conversation about changing treatment.
- Complete clearance (positive to undetectable): Associated with durable, long-term responses, particularly in patients on immunotherapy.
Your oncologist interprets Signatera results alongside imaging, tumor markers, symptoms, and your overall clinical picture. A single surprising result, whether unexpectedly positive or negative, typically leads to closer monitoring and repeat testing rather than an immediate change in treatment plan.