MRD stands for measurable residual disease (also called minimal residual disease). It refers to a very small number of cancer cells that remain in the body during or after treatment, even when standard tests like scans or blood counts show no sign of disease. These leftover cells are invisible to conventional methods but can be found using highly sensitive lab tests capable of detecting one cancer cell among a million normal cells. MRD testing has become a critical tool in blood cancers and is increasingly used in solid tumors to gauge how well treatment is working and whether cancer is likely to return.
Why the Name Changed
You may see MRD referred to as either “minimal” or “measurable” residual disease. The shift toward “measurable” reflects an important point: the cancer cells left behind aren’t necessarily minimal in significance. A tiny number of surviving cells can eventually regrow into a full relapse. Calling them “measurable” emphasizes that these cells can now be precisely quantified with modern technology, and that the measurement itself drives treatment decisions.
How MRD Testing Works
Two main laboratory approaches are used to detect MRD, each with slightly different strengths.
Flow cytometry identifies cancer cells by tagging them with fluorescent markers that recognize specific proteins on their surface. The most advanced version, developed by the international Euroflow consortium, uses an eight-color system that can spot roughly one cancer cell in 400,000 to 500,000 normal cells. In real-world lab conditions, the median sensitivity reaches about 1 in 400,000, which is close to the performance of genetic methods.
Next-generation sequencing (NGS) takes a DNA-based approach. It identifies unique genetic sequences in a patient’s cancer, then searches bone marrow or blood samples for those sequences after treatment. The FDA-authorized clonoSEQ assay from Adaptive Biotechnologies can detect one cancer cell in a million, making it the most sensitive commercially available option. It is currently approved for use in acute lymphoblastic leukemia (ALL) and multiple myeloma.
The sensitivity threshold that defines a “negative” result varies by cancer type. In acute myeloid leukemia, the cutoff is typically set at 1 in 10,000. In multiple myeloma, the bar is higher at 1 in 100,000. Under optimal conditions, both NGS and flow cytometry can push sensitivity to between 1 in 100,000 and 1 in 1,000,000.
What MRD Results Mean for Patients
An MRD-negative result means no cancer cells were detected at the predefined sensitivity threshold. It does not guarantee zero cancer cells exist, but it is one of the strongest indicators that treatment has been effective. An MRD-positive result means detectable cancer cells remain, signaling a higher risk of relapse and potentially prompting doctors to adjust or intensify treatment.
The survival differences are substantial. In multiple myeloma, a meta-analysis reported by the American Society of Hematology found that MRD-negative patients had a median progression-free survival of 60 months compared to 36 months for MRD-positive patients. At the five-year mark, 50% of MRD-negative patients remained disease-free versus just 29% of those who tested positive.
When MRD Testing Happens
MRD is not a one-time snapshot. The most common time point for testing is after the initial round of chemotherapy (called induction) or after a stem cell transplant. But there is growing interest in serial testing, meaning repeated measurements at several milestones during and after treatment, to track how the cancer responds over time. In some treatment protocols, bone marrow samples are tested at baseline, after every few treatment cycles, at the end of induction, and then every six months during maintenance therapy. Research in mantle cell lymphoma, for instance, identified the period after four cycles of treatment as the most informative single time point for MRD assessment.
MRD in Blood Cancers
Blood cancers are where MRD testing is most established. Current clinical guidelines from the National Comprehensive Cancer Network include specific recommendations for several types. In adult ALL, MRD results are used for post-treatment monitoring, risk stratification, and treatment modification. In mantle cell lymphoma, MRD testing is recommended for monitoring and risk stratification, though partly still in research settings. For follicular lymphoma and diffuse large B-cell lymphoma, MRD use is recognized but remains more research-oriented, with a specific recommendation for circulating tumor DNA-based testing in certain lymphoma cases where a biopsy isn’t feasible.
MRD in Solid Tumors
Detecting leftover cancer cells in solid tumors is trickier because there’s no single tissue (like bone marrow) to sample. Instead, doctors are turning to circulating tumor DNA, or ctDNA: tiny fragments of cancer DNA that leak into the bloodstream. A simple blood draw can capture these fragments, and specialized tests search for cancer-specific mutations within them.
Two approaches exist. Tumor-informed assays first analyze the patient’s surgical tumor sample to identify its unique mutations, then look for those exact mutations in the blood. Tumor-agnostic assays scan for common cancer-related mutations without needing a prior tumor sample. The tumor-informed approach tends to be more sensitive, while the agnostic method is faster to deploy.
Colorectal cancer is the furthest along. The large CIRCULATE-JAPAN initiative, which includes the GALAXY trial, has tracked MRD status in patients with stage II through IV colorectal cancer after surgery. Detecting ctDNA after an operation correlates with higher recurrence risk. ctDNA-guided decision making is now considered standard clinical practice for colorectal cancer in the post-surgical setting, with ongoing trials testing whether treatment can be safely skipped in patients who test negative or intensified in those who test positive.
In breast cancer, ctDNA monitoring shows striking early-warning potential. A pilot study tracking patients for up to 12 years after surgery found that ctDNA could be detected ahead of clinical or radiologic relapse with a lead time of up to 38 months. A newer patient-specific assay called CloneSight detected ctDNA positivity in 50% of patients with hormone receptor-positive early breast cancer up to 68 months before recurrence, while remaining negative in 93% of patients who never relapsed.
Lung cancer research is also advancing. Studies in non-small cell lung cancer have shown that ctDNA clearance during treatment correlates with better event-free survival and pathologic response. Multiple ongoing clinical trials are testing whether MRD-positive patients with resected stage II or III lung cancer benefit from additional therapy after surgery.
How MRD Guides Treatment Decisions
The practical value of MRD testing lies in its ability to personalize what happens next. For patients who achieve MRD negativity, there may be an opportunity to de-escalate treatment, sparing them the side effects of additional chemotherapy that they may not need. For patients who remain MRD positive, the result can trigger a switch to a different drug regimen, the addition of targeted therapy, or consideration of a stem cell transplant.
This is a shift from the traditional approach, where all patients at a given cancer stage received roughly the same post-treatment plan regardless of how deeply their individual cancer responded. MRD testing makes it possible to tailor those decisions to the biology happening inside each patient’s body rather than relying solely on imaging or surface-level blood counts that miss cancer cells lurking below their detection limits.