Minimal Residual Disease (MRD): Should You Get Tested for It After Cancer Treatment?

There are many different kinds of cancer, but they all have one thing in common: They want to grow. Cancer cells multiply quickly — that’s one of the reasons cancer is so dangerous. And it means cancer treatment is most successful when it gets rid of all the cancer in your body. Any cells left behind have the potential to grow into a new tumor.

At the end of cancer treatment, the hope is that the cancer never comes back. But sometimes cancer does reoccur. Scientists are still working to understand which factors make cancer relapse. One thing seems clear: Minimal residual disease (MRD) — that is, bits of cancer that remain in the bloodstream after cancer treatment — are linked to a higher rate of recurrence.

Scientists are designing new tests to find MRD in the blood. Although they aren’t part of routine cancer care yet, these tests are beginning to show promise as a way to predict if and when cancer will come back. 

What is minimal residual disease?

Cancer is considered cured when it’s completely removed from the body. Scientists designed many cancer treatments to do just that. But it’s extremely difficult to get rid of every single cancer cell without damaging too many healthy cells along the way. MRD occurs when small numbers of cancer cells, or parts of them, escape treatment and survive. 

Researchers know there’s a high risk of cancer returning when cancer cells are left behind. MRD refers to tiny bits of cancer DNA (deoxyribonucleic acid) that remain in the body after treatment. When testing finds MRD, it’s a sign the cancer isn’t completely gone.

Are there symptoms of minimal residual disease?

MRD doesn’t have any symptoms. It can exist after cancer treatment or during recovery from surgery or other cancer-fighting procedures. MRD can also exist later, when it seems like cancer is cured. Specific testing is the only way to know it’s there.

What is MRD testing?

An MRD test looks for evidence of cancer particles that are still in the body. The test is usually designed to detect tiny fragments of cancer DNA. It’s powerful because it can:

• Help find out if cancer treatment has been effective

• Identify people who are at risk for a relapse

• Catch relapses before the cancer has a chance to grow

• Let care teams know they can stop cancer treatment when the MRD is gone

MRD testing depends on brand-new technology that researchers are still developing. It’s pretty easy to see how MRD testing will be helpful in the future. But at this point, the medical community doesn’t have enough experience with it to comfortably rely on the results, especially when lives are at stake. 

Some MRD tests are already being used 

Although researchers are still developing much of the technology, specialized providers are already using a few MRD tests. These include: 

• ClonoSEQ: for blood cancers, such as leukemia and multiple myeloma

• Signatera: for colorectal cancer

• Invitae: for several types of solid tumors, such as breast, ovarian, skin, or pancreatic cancer

• Guardant Reveal: for colorectal, breast, and lung cancer

• InVisionFirst-Lung: for lung cancer

How does MRD testing work?

The most sophisticated MRD testing uses cutting-edge technology to figure out if there’s cancer DNA in a blood sample. Here’s how that works.

MRD testing uses a ‘liquid biopsy’

Specialists can do MRD testing on a regular sample of blood from your arm. It’s known as a “liquid biopsy” because, traditionally, the best way to check for cancer was to get a tissue biopsy. A tissue biopsy is a small sample of cells from organs or tissues near your cancer. But biopsies are inconvenient, uncomfortable, and can cause problems of their own. 

MRD tests take advantage of the fact that all of the body’s cells, including cancer cells, release genetic information into the bloodstream over time. This allows healthcare teams to pull a lot of genetic information from a sample of blood. 

MRD testing looks for ctDNA

The most advanced MRD testing detects ctDNA (circulating tumor DNA). This is a small fragment of DNA that cancer cells release, and it moves through the body in the bloodstream. Since cancer cells release it, ctDNA contains genetic information specific to that particular cancer.

There’s a large amount of normal, healthy DNA in blood already. Cutting-edge MRD tests sort through all that material to look for patterns of DNA that come from cancer. MRD testing does this in two main ways:

1. PCR (polymerase chain reaction) tests hunt for bits of DNA containing genetic patterns that are known to signal recurrent cancer.

2. Next-generation sequencing tests look for patterns of DNA that match DNA from your own cancer cells. This usually requires a tissue biopsy first to identify the unique DNA markers in your cancer.

Scientists are still trying to figure out the best way to detect MRD. The most reliable results require a tissue sample. But promising blood-only technology is beginning to emerge. Another ongoing question is how much material is needed. While a larger sample can mean a higher chance of finding MRD, very large samples are expensive and difficult to process. 

What does it mean if you have a negative or positive MRD test?

In an ideal scenario, there would be a clear answer about whether or not treatment completely got rid of your cancer. 

Unfortunately, MRD testing of a blood sample is too new for a “no” answer to be trustworthy. It’s always possible the amount of material in the sample was just too small to contain much ctDNA. Or the cancer may not be releasing much information into the bloodstream. For example, cancer in the lungs is less likely to release cancer particles into the bloodstream than cancer in the liver. 

Finding small amounts of ctDNA in a sample full of normal DNA is like finding a needle in a haystack. That means the test results are most helpful when they’re least encouraging — when there’s a positive test that found MRD. 

If you’ve completed a course of treatment for cancer and your MRD testing comes back positive, it probably means there’s still some cancer in your body. At that point, your healthcare provider might:

• Increase your dose of cancer medication

• Add another cycle of chemotherapy or radiation

• Change to a different cancer treatment plan

• Recommend additional testing

• Plan for more frequent follow-up checks

• Not make any changes at all

Who should get MRD testing after cancer treatment?

MRD testing isn’t available for every type of cancer. In some cases, MRD tests have been approved for use, but the tests don’t yet fit into standard treatment plans. 

Even when MRD testing is available, it doesn’t always make sense to use it. For example, if you know you have cancer in your body, MRD testing won’t tell you anything new. And people who have decided not to continue treating their cancer are unlikely to benefit from MRD tests.

For some types of cancer, such as multiple myeloma and other blood cancers, checking for MRD (from a bone marrow sample) is already routine. Until the medical community better understands them, the newer MRD blood tests might be done in addition to the more well-known ones. 

Although MRD testing is promising, for most cancers it’s still too new to be part of the big decisions in your treatment plan. You’ll want to talk to your oncologist about what its role might be for you. 

Does insurance cover MRD testing?

Most types of MRD testing use new technology, and they’re expensive. Insurance companies are often hesitant to cover new things that may or may not end up being useful. That said, insurance may cover MRD tests if they’re part of the treatment protocol for the type of cancer you have. 

Can you use MRD testing to diagnose cancer in someone who has never had it before?  

Many people are interested in finding a test to detect cancer in the first place. Researchers are working on finding a way to use MRD testing as a cancer screening tool. At the moment, the technology isn’t ready for this use. 

Why trust our experts?

Written by:

Kerry R. McGee, MD, FAAP

Kerry McGee, MD, FAAP, has over a decade of experience caring for babies, children, and teenagers as a primary care pediatrician. She has a special interest in adolescent health, particularly in adolescent mental health.

Edited by:

Sophie Vergnaud, MD

Sophie Vergnaud, MD, is the Senior Medical Director for GoodRx Health. An experienced and dedicated pulmonologist and hospitalist, she spent a decade practicing and teaching clinical medicine at academic hospitals throughout London before transitioning to a career in health education and health technology.

Reviewed by:

John Strickler, MD

John Strickler, MD, joined the Duke University faculty in 2011 and is now an associate professor of medicine in the division of medical oncology. His research focuses on precision cancer medicine: identification of genomic biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy.

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