Minimal Residual Disease (MRD) Test: Cancer Recurrence Risk and Results

A minimal residual disease test looks for very small amounts of cancer that remain after treatment, often at levels too low to appear on routine scans, blood counts, or a microscope examination. In blood cancers, specialists increasingly use the term measurable residual disease because even highly sensitive testing has a detection limit and cannot prove that every cancer cell is gone. In solid tumors, MRD testing most often searches blood for circulating tumor DNA, or ctDNA, after surgery or other treatment intended to cure the cancer.

An MRD result can sharpen estimates of relapse risk, show how deeply a cancer has responded, and sometimes help guide additional treatment or monitoring. Its meaning depends on the cancer type, test method, sample, timing, and sensitivity. A positive result usually signals a higher chance of recurrence, while a negative result lowers risk but does not guarantee cure. Results should therefore be interpreted with the oncology team that ordered the test.

• A positive MRD result means cancer-related cells or molecular markers were detected above the assay’s validated limit.
• A negative result means the test did not detect disease, not that recurrence is impossible.
• MRD can be measured by flow cytometry, PCR, next-generation sequencing, or ctDNA testing, depending on the cancer.
• Testing is often timed after treatment, before or after transplant, and during follow-up; the ideal schedule is cancer-specific.
• Changes over several tests are often more informative than one isolated result.
• Do not change treatment based on a commercial MRD report without reviewing the result with the treating oncology team.

Table of Contents

• What MRD Testing Measures
• Why and When MRD Is Ordered
• MRD Test Methods and Sensitivity
• Samples, Timing, and Preparation
• How to Interpret MRD Results
• How MRD Is Used in Different Cancers
• Limitations and Misleading Results
• Next Steps After an MRD Result

What MRD Testing Measures

MRD is cancer that remains after treatment but is present below the detection level of conventional evaluation. A person may have normal blood counts, no visible mass on imaging, and no obvious malignant cells under the microscope while a more sensitive assay still detects an abnormal cell population or tumor-derived genetic material.

In leukemia, lymphoma, and multiple myeloma, MRD testing may examine bone marrow or blood for abnormal cells, fusion transcripts, mutations, antigen patterns, or rearranged immune-receptor sequences. The target must be sufficiently characteristic of the person’s cancer to separate disease from normal cells. Some targets, such as BCR::ABL1 in chronic myeloid leukemia or PML::RARA in acute promyelocytic leukemia, can be measured with highly standardized molecular assays. Other cancers require a combination of markers or a patient-specific sequence.

In solid tumors, molecular residual disease usually refers to ctDNA released from microscopic cancer deposits into plasma. A circulating tumor DNA test may track mutations selected from the removed tumor or use a broader panel that looks for tumor-associated sequence and methylation patterns without creating a fully personalized assay. Detectable ctDNA after curative-intent treatment strongly correlates with higher recurrence risk in many studies, but whether changing therapy solely because of a positive result improves survival is still being tested for several tumor types.

MRD is not a universal substance with one normal range. It is a measurement concept. A report may express disease as a percentage of cells, number of abnormal cells per million cells, copies of a molecular transcript, variant molecules per milliliter, variant allele frequency, or simply detected/not detected. The laboratory’s method, limit of detection, limit of quantification, and specimen quality are essential parts of the result.

The word “minimal” can also mislead. A tiny detectable amount may carry major prognostic importance, while an undetectable result may still leave disease below the assay’s reach. For this reason, many hematology groups prefer “measurable residual disease.”

Why and When MRD Is Ordered

Doctors order MRD testing when the result can add information beyond routine response assessment. Common purposes include measuring treatment depth, estimating relapse risk, selecting the intensity or duration of therapy, planning stem-cell transplantation, and detecting molecular recurrence before symptoms or imaging changes appear.

A baseline tumor or blood sample may be needed to identify a trackable marker. Later samples are compared with that marker. Testing points vary by disease, but common moments include:

• after induction or initial treatment;
• after consolidation therapy;
• before stem-cell transplantation;
• at defined times after transplantation;
• at the end of a fixed treatment course;
• during maintenance therapy;
• during surveillance after surgery for a solid tumor; and
• when blood counts, symptoms, or imaging raise concern for recurrence.

In acute leukemia, an early MRD response can separate people with otherwise similar-looking remissions into substantially different risk groups. A bone marrow that contains fewer than 5% blasts meets a traditional morphologic remission criterion, yet sensitive testing may identify one leukemia cell among 10,000 or more normal cells. That additional information can influence post-remission planning, although the decision also includes age, genetic risk, treatment tolerance, donor availability, and patient preferences.

In multiple myeloma, MRD helps describe the depth of response after therapy. Clinical trials often use assays with sensitivity of at least one malignant cell in 100,000 cells, written as 10^-5, and sometimes 10^-6. A sustained negative result is generally more favorable than a single negative test, but treatment decisions should still follow the full clinical picture.

For resected solid tumors, ctDNA testing is commonly performed several weeks after surgery to reduce interference from tissue injury and allow short-lived cell-free DNA to clear. The exact window differs among studies and commercial assays. Testing too soon may reduce the tumor fraction in a large background of normal cell-free DNA, while testing too late could delay adjuvant treatment. Oncologists balance these factors with the treatment schedule.

MRD testing is not the same as population cancer screening. It is usually used after a known cancer has been diagnosed and characterized. It also does not replace pathology, standard staging, or recommended surveillance imaging.

MRD Test Methods and Sensitivity

The best method depends on the cancer’s biology and the marker available. Laboratories should validate each assay for its intended specimen and disease.

Multiparameter flow cytometry

Flow cytometry passes cells through lasers and measures combinations of proteins on each cell. In leukemia and myeloma, abnormal cells may show a pattern that differs from normal maturation. Modern panels can evaluate hundreds of thousands to millions of cells and often reach sensitivities around 10^-4, or one abnormal cell among 10,000, when the specimen is adequate.

Flow cytometry is relatively fast and can work even when no single mutation is trackable. Its accuracy depends on sample quality, the number of cells collected, instrument design, antibody panels, analyst expertise, and whether treatment has changed the cancer’s protein pattern. Bone marrow dilution with peripheral blood can produce a falsely reassuring result.

Quantitative and digital PCR

Polymerase chain reaction amplifies a specific DNA or RNA target. Quantitative PCR and digital PCR can detect fusion transcripts or mutations at very low levels, sometimes around 10^-4 to 10^-6. These methods are especially useful when a stable, well-defined target is present. Examples include the BCR-ABL1 test in CML, NPM1 mutation monitoring in acute myeloid leukemia, and PML::RARA monitoring in acute promyelocytic leukemia.

PCR is highly sensitive but usually narrow. It cannot monitor a cancer that lacks the selected target, and a mutation that disappears through clonal evolution may no longer represent all remaining disease.

Next-generation sequencing

Next-generation sequencing, or NGS, can examine many DNA or RNA targets at once. In leukemia, it may track mutations or rearranged immunoglobulin and T-cell receptor sequences. In myeloma and lymphoid cancers, patient-specific receptor sequences can provide sensitive tracking. Error-correction methods help distinguish true low-frequency variants from sequencing noise.

An NGS result must account for age-related clonal hematopoiesis. Mutations in genes such as DNMT3A, TET2, and ASXL1 may persist in blood-forming cells even when AML has cleared. Detecting one of these mutations does not always mean active leukemia remains. The laboratory and hematologist interpret which variants are suitable MRD markers.

In solid tumors, a liquid biopsy can use tumor-informed or tumor-naive methods. Tumor-informed assays sequence the original tumor and design a personalized panel to track selected variants. Tumor-naive assays analyze plasma without requiring a matched tumor, often combining multiple genomic or epigenomic signals. Tumor-informed methods may improve specificity for that person’s cancer, while tumor-naive approaches can be faster and avoid dependence on available tissue. Performance varies by cancer, stage, tumor shedding, blood volume, and assay design.

How sensitivity is reported

Analytical sensitivity is the lowest level an assay can reliably detect under validation conditions. Clinical sensitivity is the chance that the assay is positive when residual cancer is truly present. These are not identical. A test capable of detecting a variant at 0.01% in a reference sample may still miss disease if the tumor does not release DNA into blood or the collected marrow does not contain the residual clone.

Reports may state a limit of detection, such as 0.01%, and a limit of quantification, below which the target may be detected but not measured accurately. A “detected below quantifiable range” result should not be treated as zero or as a precise number.

Samples, Timing, and Preparation

MRD testing may use bone marrow aspirate, peripheral blood, plasma, or occasionally another body fluid. The order should identify the disease, treatment stage, target, and appropriate assay.

Bone marrow is often preferred for AML and myeloma because disease can be more concentrated there than in blood. The procedure usually involves local anesthetic and collection from the back of the hip bone. A first-pull aspirate may contain the highest marrow concentration. If the sample is hemodiluted, the report may warn that sensitivity is reduced.

Peripheral blood is easier to collect and supports frequent monitoring. It is standard for some molecular markers, including BCR::ABL1 in CML, and may be useful for NPM1 or other targets in selected settings. However, a negative blood result can be less sensitive than a negative marrow result for some diseases.

For ctDNA MRD, blood is collected in tubes designed either for rapid plasma processing or for stabilizing blood cells during transport. Delayed or improper handling can cause white blood cells to release normal DNA, diluting the tumor signal. Many assays request two or more tubes to obtain enough plasma.

Most MRD blood tests require no fasting. Continue medications unless the clinical team gives different instructions. Before a marrow procedure, the team may review anticoagulants, bleeding disorders, allergies, and infection risk. Patients should tell the laboratory about a recent blood transfusion, stem-cell transplant, other cancer, or pregnancy when relevant because these circumstances can complicate molecular interpretation.

Timing matters as much as preparation. A result should be compared with the correct treatment milestone and, when possible, the same assay type. Switching laboratories or platforms can change sensitivity and reporting units. Serial testing is most interpretable when collection and methods remain consistent.

How to Interpret MRD Results

An MRD report should be read as a complete laboratory statement, not reduced to the word positive or negative. Important fields include the marker, specimen, assay method, measured level, sensitivity achieved, quality warnings, comparison with prior results, and laboratory interpretation.

Report term	Usual interpretation	Important caution
Detected or positive	The disease-associated marker was found above the assay’s detection criteria.	Risk and treatment implications depend on level, timing, disease, and method.
Not detected or negative	No marker was found at the sensitivity achieved in that sample.	Disease may still exist below the limit or outside the sampled compartment.
Quantifiable	The signal is strong enough for the laboratory to report a reliable numeric level.	Units and calibration may differ between assays.
Detected, not quantifiable	A low signal was identified, but it is below the range for accurate measurement.	Repeat testing may be needed to confirm a trend.
Indeterminate or inadequate	The test could not provide a reliable positive or negative answer.	Low cell count, poor DNA quality, hemodilution, or assay interference may be responsible.

A positive result usually predicts a higher risk of relapse than a negative result at the same treatment point. It does not mean that clinical recurrence is certain or immediate. Some low-level signals clear with ongoing therapy; others remain stable; still others rise before overt relapse.

A negative result is favorable only in the context of adequate sensitivity. “MRD negative at 10^-5” means no disease was detected down to approximately one target cell among 100,000 evaluated cells under that assay’s conditions. It is stronger evidence than a negative result achieved only at 10^-3, but neither proves the absence of every malignant cell.

Trends help distinguish biological change from sampling variation. A falling molecular level may indicate response. A confirmed rise, reappearance after negativity, or conversion from negative to positive can signal molecular relapse. Many protocols require confirmation with a second sample, especially when the first signal is near the detection limit.

Do not compare percentages from different methods as though they are interchangeable. Flow cytometry, PCR, NGS, and ctDNA measure different analytes. Even two commercial ctDNA assays may track different variants and use different calling thresholds.

How MRD Is Used in Different Cancers

MRD is deeply integrated into some blood-cancer pathways and remains investigational or selectively used in many solid tumors.

Acute leukemias

In acute lymphoblastic leukemia, MRD after induction and consolidation is one of the strongest prognostic factors. Results may affect treatment intensity, transplant decisions, and use of therapies directed at persistent disease. Assays commonly use flow cytometry, PCR, or NGS and often evaluate thresholds around 10^-4, though protocols vary.

In AML, flow cytometry and molecular markers are used at specified milestones. NPM1 is a particularly informative marker when present at diagnosis; an NPM1 mutation test can be followed by quantitative molecular testing. Fusion genes and selected mutations may also be tracked. Persistent DNMT3A, TET2, or ASXL1 variants alone require caution because they may reflect clonal hematopoiesis rather than residual AML.

Acute promyelocytic leukemia is monitored with sensitive PML::RARA PCR. Confirmed molecular persistence or recurrence can require rapid specialist action because treatment before overt hematologic relapse may improve control. The PML-RARA test has disease-specific collection and confirmation recommendations.

Chronic myeloid leukemia and lymphoid cancers

CML monitoring uses BCR::ABL1 transcript levels on the International Scale rather than a simple positive/negative MRD label. Milestones at defined months guide evaluation of tyrosine kinase inhibitor response. Very deep and sustained molecular responses may support a supervised treatment-free remission attempt in carefully selected patients.

In chronic lymphocytic leukemia, lymphoma, and multiple myeloma, MRD is increasingly used in trials and selected clinical decisions. The acceptable specimen and threshold differ. In myeloma, marrow NGS or flow may be combined with imaging because patchy disease outside the sampled site can remain.

Solid tumors

Post-treatment ctDNA has strong prognostic value in colorectal, breast, lung, bladder, and other cancers. A positive result after surgery identifies a group with a high recurrence rate in many cohorts, often months before radiographic recurrence. However, prognostic value does not automatically establish that an MRD-directed treatment change improves survival.

Some clinical settings now incorporate ctDNA selectively, while others recommend use mainly in trials. Decisions may involve adjuvant chemotherapy escalation, de-escalation, surveillance frequency, or enrollment in an MRD-guided study. Tumor genomic testing may help define the variants that a tumor-informed assay will track, but broad tumor profiling and MRD testing answer different questions.

Limitations and Misleading Results

MRD testing can fail because the biological signal is absent from the sample, the sample is inadequate, or the assay does not track the right marker. Understanding these limits prevents overconfidence.

A false-negative result can occur when:

• the residual tumor is too small or releases little DNA;
• disease is confined to a site that does not shed into blood;
• marrow involvement is patchy and the needle samples an uninvolved area;
• the marrow aspirate is diluted with blood;
• too few cells or too little plasma is analyzed;
• treatment changes the abnormal protein pattern used by flow cytometry;
• the tracked mutation is lost while another malignant clone survives; or
• the sample is collected at an unfavorable time.

A false-positive or clinically misleading result can occur because of sequencing artifacts, contamination, a second malignancy, donor-derived cells after transplant, or clonal hematopoiesis. Matched white-cell sequencing can help distinguish blood-cell mutations from tumor-derived ctDNA in some assays.

Results near the cutoff may fluctuate. A single low positive should be interpreted with assay precision, prior levels, specimen quality, and the consequences of acting. Repeating the test can be safer than making an irreversible treatment decision from an uncertain signal.

MRD also raises emotional and practical issues. Molecular detection may precede visible relapse by months, creating a period in which recurrence risk is known but the best intervention is uncertain. Insurance coverage and access vary. Commercial reports may use proprietary methods that are difficult to compare or reproduce.

Most importantly, a test can have clinical validity without proven clinical utility. Clinical validity means the result predicts an outcome, such as recurrence. Clinical utility means using the result to change care improves outcomes compared with standard management. For several solid tumors, ongoing randomized trials are still establishing that second step.

Next Steps After an MRD Result

Review the report with the clinician who understands the cancer, treatment history, and assay. The next step may be continued monitoring, confirmation, a marrow examination, imaging, treatment adjustment, transplant planning, or a clinical trial.

For a positive result, ask:

• Was the signal clearly above the detection and quantification limits?
• Is this marker known to represent the cancer rather than clonal hematopoiesis?
• How does the result compare with the previous measurement?
• Does the timing match a validated treatment milestone?
• Should the result be confirmed in blood, marrow, or a second sample?
• Is there evidence that changing treatment at this point improves outcomes?
• Is an MRD-guided clinical trial available?

For a negative result, ask what sensitivity was actually achieved and whether the sample was adequate. Continue standard follow-up unless the oncology team specifically changes the plan. A negative MRD result should not be used to skip appointments, imaging, maintenance therapy, or recommended surveillance without medical guidance.

Seek prompt medical evaluation for symptoms that could indicate relapse or a treatment complication, regardless of the latest MRD result. These can include unexplained fever, persistent infections, unusual bruising or bleeding, worsening fatigue, new bone pain, enlarging lymph nodes, unexplained weight loss, shortness of breath, neurologic symptoms, or a new persistent localized symptom. MRD is one piece of surveillance, not a substitute for clinical assessment.

A useful result is one that answers a defined question with a validated assay at the right time. When those conditions are met, MRD testing can provide a much finer view of cancer response than conventional tests alone.

References

• Measurable residual disease in hematologic malignancies 2025 (Review)
• Measurable Residual Disease Detection in Acute Myeloid Leukemia: Current Challenges and Future Directions 2024 (Review)
• A review of trials investigating ctDNA-guided adjuvant treatment strategies 2024 (Review)
• Minimal residual disease (MRD) detection in solid tumors using circulating tumor DNA: a systematic review 2023 (Systematic Review)
• ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group 2022 (Position Statement)

Disclaimer

MRD results are disease-, method-, and time-specific and cannot diagnose recurrence or determine treatment by themselves. Discuss any positive, negative, indeterminate, or changing result with the oncology team that knows the assay and your full clinical history. Seek urgent care for severe bleeding, breathing difficulty, neurologic symptoms, or other acute illness rather than waiting for repeat testing.