MRD Positive: What It Means and What to Do Next

An MRD-positive result means that after cancer treatment, small numbers of cancer cells are still detectable in your body even though scans and standard exams show no visible disease. MRD stands for minimal residual disease (sometimes called measurable or molecular residual disease), and testing positive for it after achieving what looks like remission is one of the strongest predictors of relapse across many cancers. That does not mean relapse is inevitable, and what your medical team does with the information depends on the type of cancer, the testing method, and your individual situation.

Why MRD Matters After Remission

Many people finish treatment and hear some version of “the cancer is gone” based on imaging or physical examination. And in one sense, it is gone: scans are clear, blood counts look normal, and the disease meets the criteria for complete remission. But modern laboratory tests can look far deeper than a CT scan or a blood smear. They can find one cancer cell among hundreds of thousands or even millions of normal cells. When those tests find residual cancer cells, the result is MRD-positive.

The reason clinicians care so much about this result is straightforward. Even after dramatic responses to treatment, including complete remission by every standard measure, many patients retain residual disease that eventually drives relapse.¹ MRD testing gives doctors a way to see whether this leftover disease is present before it has a chance to grow back into something visible on imaging. In blood cancers such as leukemia and myeloma, the link between MRD positivity and relapse risk has been well-established for years. In solid tumors like colon cancer and breast cancer, the evidence is newer but rapidly growing.

How MRD Is Detected

The specific test you receive depends on your cancer type and where your treatment is happening. In blood cancers, MRD is typically measured from bone marrow samples or peripheral blood using one of two main approaches. Flow cytometry identifies cancer cells by the distinctive combination of proteins on their surface. Molecular techniques, including next-generation sequencing, look for cancer-specific DNA sequences. Both can reach extraordinary sensitivity, finding as few as one cancer cell in a million, though results can vary between laboratories because the choice of markers, the number of cells analyzed, and the threshold for calling a result “positive” are not fully standardized.²

For solid tumors, conventional imaging is not sensitive enough to catch MRD.³ Instead, clinicians increasingly rely on liquid biopsies, blood draws that look for circulating tumor DNA (ctDNA), tiny fragments of DNA shed by cancer cells into the bloodstream. ctDNA testing can also pick up circulating tumor cells and tumor-specific markers.⁴ Because a blood draw is far less invasive than a tissue biopsy, liquid biopsy has opened a practical diagnostic window for cancers where repeat biopsies would be difficult or risky.

MRD Positive in Blood Cancers

Blood cancers were the first area where MRD testing became routine, and the evidence here is the most mature. In acute lymphoblastic leukemia (ALL), a shift from MRD-positive to MRD-negative during treatment is one of the clearest signals of a good outcome. When MRD persists or its levels rise, the hazard of relapse is high.⁵ This information often reshapes the treatment plan in real time: patients whose MRD clears quickly may be spared more aggressive therapy, while those who stay MRD-positive may be switched to a different regimen or referred for a stem cell transplant.

In acute myeloid leukemia (AML), international guidelines from the European LeukemiaNet now provide specific MRD thresholds and define what counts as an MRD response, reflecting how central the measurement has become to treatment decisions.⁶ Decisions about whether to proceed with transplant, how intense conditioning therapy should be, and whether maintenance therapy is needed are all influenced by MRD status.

Multiple myeloma offers some of the most striking numbers. In one set of clinical trials, achieving MRD-negativity was associated with an 82% reduction in the risk of disease progression and an 88% reduction in the risk of death. Only about 7% of patients who reached MRD-negative status went on to progress, and half of those who did had disease that had spread outside the bone marrow.⁷ Those numbers make it clear why reaching MRD-negativity has become the treatment goal in myeloma, and why staying MRD-positive after frontline therapy is taken seriously.

MRD Positive in Solid Tumors

Using MRD testing in solid cancers is a more recent development, but it is progressing quickly. In colorectal cancer, a landmark trial demonstrated that ctDNA testing after surgery for stage II colon cancer could guide chemotherapy decisions. Patients whose ctDNA was positive after surgery received chemotherapy, while those whose ctDNA was negative were spared it. The result: the ctDNA-guided group had nearly half as many patients receiving chemotherapy compared to the standard-care group (about 15% versus 28%), with no compromise in two-year recurrence-free survival.⁸ That is a big deal for patients, because it means many people who would otherwise receive months of chemotherapy with real side effects can safely skip it.

The flip side is just as important. If you are ctDNA-positive after surgery for a solid tumor, that positive result flags you as someone at higher risk for recurrence, which may prompt your oncologist to recommend additional chemotherapy or consider enrolling you in a clinical trial testing newer targeted therapies or immunotherapy combinations.⁹ The logic is to intervene before the residual disease grows into visible metastases, at a stage when the cancer burden is smallest and potentially most vulnerable to treatment.

Similar ctDNA-guided approaches are being studied in breast, lung, bladder, and pancreatic cancers. The underlying principle is the same everywhere: detect residual disease earlier than imaging can, and use that information to decide who needs more treatment and who does not.

What Your Team May Recommend After an MRD-Positive Result

The specific next step varies widely based on cancer type, how far along you are in treatment, and what options remain available. There is no universal playbook, but the responses tend to fall into a few categories.

• Treatment intensification: If your current therapy has not eliminated MRD, your team may switch to a stronger or different regimen. In ALL, for example, patients who remain MRD-positive after initial chemotherapy may be moved to drugs specifically designed to clear residual disease.
• Targeted MRD therapy: Some drugs now specifically target MRD. Blinatumomab, a bispecific antibody approved for MRD-positive B-cell ALL, achieved a complete MRD response in about 78% of evaluable patients in a key study, and those who responded had significantly longer relapse-free and overall survival compared to non-responders.¹⁰ Its approval specifically for MRD-positive ALL marked a turning point in how the field thinks about treating residual disease rather than waiting for full relapse.¹¹
• Stem cell transplant: For some blood cancers, an MRD-positive result after initial therapy may tip the decision toward proceeding with a transplant. MRD status before transplant is one of the factors clinicians weigh when deciding on conditioning intensity and post-transplant monitoring strategies.¹²
• Adjuvant chemotherapy in solid tumors: If ctDNA is detected after surgery, your oncologist may recommend chemotherapy that would otherwise have been considered optional for your cancer stage.
• Closer surveillance: In some situations, especially when the MRD level is very low or the clinical significance in your specific cancer is still being established, the recommendation may be more frequent monitoring rather than immediate treatment changes.

The choice depends on the balance between the added toxicity of more treatment and the risk of relapse signaled by MRD positivity. Your oncologist should be walking you through this tradeoff explicitly, because the right answer is not always “treat harder.”

When an MRD-Positive Result Might Be Wrong

No test is perfect, and understanding the potential for false positives is especially important with MRD testing because the consequences of a positive result can be aggressive treatment changes. The most well-known source of false-positive ctDNA results is clonal hematopoiesis of indeterminate potential, or CHIP, a condition where blood-forming stem cells acquire mutations that look like cancer mutations but are not actually from a tumor. CHIP becomes more common with age and can significantly confound ctDNA detection.¹³

Modern testing platforms use bioinformatics filters to screen out CHIP-related mutations, often by comparing the ctDNA results against sequencing of the patient’s white blood cells. This comparison helps identify whether a mutation came from the tumor or from normal age-related changes in blood cells.¹⁴ But CHIP is not the only source of confusion. Aberrant methylation patterns from non-cancer conditions, such as inflammatory diseases, can also trigger false-positive results on certain liquid biopsy assays, and this issue is less well-recognized than CHIP.¹⁵

If you receive an unexpected MRD-positive result, particularly one that does not align with your clinical picture, it is reasonable to ask your oncologist whether the result has been confirmed with repeat testing or a different method. A single positive result on one platform should not automatically trigger a major treatment change without clinical context.

Blood Versus Bone Marrow and the Discordance Problem

In blood cancers, MRD is traditionally measured from bone marrow aspirates, which requires a needle biopsy from the hip bone. This is uncomfortable and cannot be done as frequently as a simple blood draw. Naturally, there has been interest in using peripheral blood instead, and studies suggest the two are highly correlated. In adult ALL patients, next-generation sequencing MRD from blood and bone marrow showed a correlation of 0.87, with sensitivity and specificity for blood-based testing both around 87–90%.¹⁶

However, about 12% of paired samples were discordant, split evenly between cases where blood was positive but marrow was negative and vice versa. That means roughly one in eight patients would get a different answer depending on which sample was tested. For now, bone marrow remains the standard reference in most blood cancers, but peripheral blood testing is gaining ground, especially for monitoring between scheduled marrow biopsies. If your team switches between sample types across visits, ask whether the results are being interpreted in light of that difference.

MRD-Guided Clinical Trials

One of the most active areas in oncology right now is designing clinical trials around MRD results rather than traditional staging or risk factors alone. The idea is that MRD status can direct treatment up or down depending on whether you are positive or negative, rather than giving every patient the same regimen.

In colon cancer, the UK’s TRACC Part C trial is testing whether patients who are ctDNA-negative after surgery can safely skip adjuvant chemotherapy while maintaining good disease-free survival.¹⁷ In myeloma, the RADAR trial simultaneously tests both escalation and de-escalation strategies guided by MRD results, meaning patients whose MRD clears may be given less treatment, while those who remain MRD-positive get more.¹⁸

These trials represent a fundamental shift from treating patients based on the cancer they started with toward treating them based on how their body is actually responding to therapy. For patients who are MRD-positive, this means an MRD result is not just a prognostic number. It could determine which arm of a trial you qualify for, and enrollment in such a trial may offer access to newer therapies that are not yet standard.

The Regulatory Shift Around MRD

In April 2024, the FDA’s Oncologic Drugs Advisory Committee voted unanimously to support MRD-negative complete response as an early endpoint for accelerated drug approval in multiple myeloma.¹⁹ This is a significant regulatory milestone. Traditionally, new cancer drugs needed to show improvements in progression-free survival or overall survival, which can take many years to demonstrate. Allowing MRD negativity to serve as a surrogate endpoint means that drugs capable of driving deep responses could reach patients faster.

For patients who are currently MRD-positive, this regulatory change has indirect but real implications. It accelerates the pipeline of new therapies aimed specifically at eliminating residual disease. It also means the field is formally recognizing MRD status as something meaningful enough to base drug approvals on, which strengthens the case for routine MRD monitoring in clinical practice.

The Emotional Weight of Living With MRD Positivity

Getting an MRD-positive result can feel uniquely distressing in a way that differs from the original diagnosis. You finished treatment. You may have been told things look good. And then a highly sensitive test tells you that cancer cells are still there. The psychological impact of that information is real. Research on leukemia patients receiving MRD results has found that disease stage, relapse status, and social circumstances all predict levels of emotional suppression, and patients who feel constrained from expressing their emotions tend to fare worse psychologically.

One important thing to understand is what MRD positivity does not mean. It does not mean your treatment failed. It does not mean the cancer is back in the way you originally experienced it. It means there is a measurable signal that your team can act on, and in many cases, the very fact that it was caught this early is what makes it treatable. Some clinicians have noted that one of the main benefits of MRD testing in solid tumors has been in estimating recurrence risk and likelihood of cure, which can be communicated to patients to help them understand their situation, even when the evidence for improving outcomes by acting on MRD results is still developing.²⁰

If you are struggling with the uncertainty, ask your oncologist to be specific about what the result means for your prognosis and what concrete steps follow. Vague reassurance is less helpful than a plan, even if the plan is “we monitor more closely.” Support groups specifically for people in remission dealing with MRD results are becoming more common and may be worth seeking out.

Controversies and Unresolved Questions

MRD testing is not without critics, and some of the concerns are legitimate. One major controversy is lead-time bias: detecting cancer traces earlier does not automatically mean patients live longer. It is possible that MRD testing simply gives more warning time before an inevitable recurrence, without changing the outcome. In solid tumors especially, the evidence that acting on MRD-positive results actually improves survival, rather than just detecting recurrence sooner, is still being built.²⁰ That same review notes that acting on MRD results can carry harms: added costs, more diagnostic procedures, patient anxiety, and in the case of false positives, exposure to unnecessary toxic therapies.

There is also the standardization problem. Different laboratories use different marker panels, different sensitivity thresholds, and different criteria for calling a result positive.² A result from one lab may not be directly comparable to a result from another. This matters both for individual patients whose care might shift between centers and for clinical trials trying to use MRD as a reliable endpoint. Efforts to standardize MRD testing are underway, with consensus guidelines emerging in AML and myeloma, but full harmonization across institutions and cancer types is still years away.

Emerging Technologies That May Change the Landscape

The sensitivity of MRD detection keeps improving. Multi-omics approaches, which combine multiple types of molecular data such as DNA mutations, methylation patterns, DNA fragment size analysis, and protein markers, are showing promise for detecting residual disease more reliably than any single approach alone.²¹ Artificial intelligence is also being integrated into these platforms to improve diagnostic sensitivity and reduce false-positive rates.²²

What this could mean for patients in practical terms is that future MRD tests may be both more sensitive (catching smaller amounts of residual disease) and more specific (producing fewer false positives). A more reliable test makes the clinical decision easier, because clinicians can trust the result and act on it with greater confidence. For now, though, the technology is evolving faster than the clinical evidence to support acting on its results. The most responsible approach, for patients and clinicians alike, is to view MRD results as one piece of a larger clinical picture rather than a single number that dictates the next move.