What minimal-residual-disease testing is, and what it actually changes

After surgery removes a tumour, the hardest question in cancer care is often invisible: did any cancer cells survive? Scans cannot see a few thousand stray cells, so for decades the answer was inferred from the odds — the tumour's size, its grade, whether it had reached lymph nodes — and patients were offered chemotherapy accordingly, knowing many were being treated who did not need it. Minimal residual disease testing is an attempt to replace that inference with a measurement.

What MRD testing measures

Tumours shed fragments of DNA into the bloodstream, called circulating tumour DNA, or ctDNA [s2]. An MRD test looks for that tumour DNA in a blood sample drawn after surgery. If it is present, cancer cells remain somewhere in the body even though nothing shows on imaging — minimal residual disease. If it is absent, the odds of hidden cancer are much lower. The evidence consistently shows that residual disease detected this way is closely associated with later recurrence, which is what makes ctDNA a promising marker for identifying the patients at higher risk who may benefit from more treatment — and, just as importantly, those who may not [s2].

Many MRD tests are tumour-informed: the specific mutations in a person's resected tumour are sequenced first, then the blood is checked for those exact fingerprints, which makes the test highly specific to that individual's cancer [s2].

What one trial showed it can change

The clearest demonstration that MRD testing can change care, rather than merely predict outcomes, is the DYNAMIC trial. It enrolled 455 patients with stage II colon cancer — a group where the benefit of post-surgery chemotherapy has long been debated — and randomly assigned them, in a 2-to-1 ratio, to have treatment guided either by ctDNA results or by standard clinical features [s1]. In the ctDNA-guided group, only patients with a positive ctDNA test were given chemotherapy; those who tested negative were not treated [s1].

The result was a reduction in treatment without a cost in outcomes. Chemotherapy was used in 15 percent of the ctDNA-guided group versus 28 percent under standard management [s1] — roughly halving the number of people treated. Two-year recurrence-free survival was 93.5 percent in the ctDNA-guided group and 92.4 percent under standard management, meeting the trial's threshold for non-inferiority [s1]. In effect, the test identified patients who could safely skip chemotherapy and spared them its toxicity.

The trial also showed the flip side — that a positive result marks real risk. Three-year recurrence-free survival was 86.4 percent among ctDNA-positive patients who received chemotherapy, against 92.5 percent among ctDNA-negative patients who did not [s1]. A positive test identifies people who genuinely need more, even after treatment.

What it does not yet settle

DYNAMIC is one trial, in one cancer, at one stage, and its power was in de-escalation — using a negative test to withhold treatment. The harder question is the opposite one: when a test is positive, does adding or intensifying treatment actually improve survival, rather than just flagging a worse prognosis? That is still largely unresolved across cancer types, and it is where much of the current research sits. Reviews of the field describe MRD testing as a promising tool whose clinical utility is still being established, with real challenges in detection thresholds, standardisation and knowing how to act on results [s2]. A positive MRD test tells a clinician that risk is elevated; it does not by itself prove that any particular response will lower that risk.

What this means for a reader

MRD testing is one of the more concrete arrivals of precision oncology: a blood test that can, in at least one well-defined setting, personalise the decision about chemotherapy after surgery [s1]. But it is not yet a general-purpose test that applies to every cancer, and a result — positive or negative — is a piece of evidence to be weighed by an oncology team alongside everything else, not a verdict on its own. Where and how it should guide treatment is an active clinical question, and whether it is appropriate for a given patient is a decision for the specialists managing their care.

Sources

• [s1] Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer (DYNAMIC), NEJM, 2022-06-04
• [s2] Circulating Tumor DNA and Minimal Residual Disease (MRD) in Solid Tumors, Frontiers in Oncology, 2021-11-18