Medically Reviewed by John Strickler, MD: Professor of Medicine; Co-leader, Duke Cancer Institute Molecular Tumor Board; Duke University
Over the past five years, CancerConnect’s online community has received thousands of questions from patients and caregivers trying to understand ctDNA and minimal or molecular residual disease (MRD) testing and what these results really mean for their care. ctDNA‑based MRD testing is increasingly used to help doctors detect tiny amounts of remaining cancer, estimate the risk of recurrence, and personalize decisions about treatment and follow‑up. This FAQ was created to answer the most common questions asked and to help you feel more informed and prepared when you talk with your care team about MRD testing.
 | Webinar: Is my cancer coming back? How ctDNA Testing Can Help Inform Colorectal Cancer Management – John Strickler, MD |
What is ctDNA and MRD testing?
Minimal or molecular residual disease (MRD) is the term doctors use when a very small amount of cancer remains after treatment—too little to be seen on scans but still important to detect. Circulating tumor DNA (ctDNA) refers to tiny fragments of cancer DNA that tumor cells release into the bloodstream. ctDNA‑based MRD testing is designed to detect these tiny traces of cancer DNA in blood, which can be a sign that cancer is still present or may be returning, even if scans look normal.
How is MRD testing different from regular scans or blood tests like CEA?
Imaging tests (such as CT, MRI, or PET scans) show tumors only when they are large enough to see, while MRD testing can sometimes detect colorectal cancer DNA weeks, months or even years before anything appears on scans. CEA is a tumor marker blood test that has been used for many years to help monitor colorectal cancer, but ctDNA/MRD tests look directly for DNA changes from your tumor and may pick up problems earlier. Your doctor will usually consider MRD results together with CEA levels, scans, and exams rather than relying on a single test.
How does MRD testing work?
Most MRD tests are “personalized” or “tumor-informed,” meaning they start with a tumor to identify its unique DNA changes. A custom test is then created, and future blood draws are checked for those same DNA changes to see if cancer DNA is still present in your bloodstream.
Who might benefit from MRD testing?
MRD testing may be helpful if you have had surgery and treatment with curative intent and your scans show no evidence of disease, if you have a higher risk of recurrence (for example, some stage II, most stage III, or resected stage IV colorectal cancers), or if your cancer has recurred before and you and your doctor want closer monitoring between scans. It can also help some patients and care teams feel more informed about recurrence risk over time.
When is MRD testing usually done for colorectal cancer?
Your doctor may consider ctDNA/MRD testing after colorectal cancer surgery to check for remaining cancer DNA, during or after chemotherapy to track how well treatment is working, and during follow‑up visits to watch for early signs of recurrence. Testing is often repeated over time—for example, every few months—as part of ongoing surveillance, based on your stage, treatment plan, and preferences.
What can MRD test results show?
MRD results generally fall into two main categories:
- MRD negative: No tumor DNA is detected in your blood above the test’s limit at that time, which is usually a reassuring sign and is linked in studies to a lower risk of recurrence and improved prognosis.
- MRD positive: Tumor DNA is found in your blood, which may mean colorectal cancer is still present or could be starting to return, even if scans and CEA are normal.
Your doctor will interpret these results in the context of your cancer stage, pathology, treatment history, and other test findings.
How can MRD testing help guide treatment decisions and follow-up?
MRD results can help your care team:
- Detect recurrence earlier and consider starting treatment sooner.
- Track how well your current treatment is working over time.
- Decide whether to continue, change, or stop certain therapies, especially if MRD stays positive or becomes negative.
- In some situations, avoid unnecessary or prolonged treatment if MRD is repeatedly negative, which may reduce side effects and improve quality of life.
Can MRD testing help decide if I need chemotherapy after surgery?
For some people with stage II or stage III colorectal cancer, ctDNA/MRD results may help the care team decide whether chemotherapy is likely to help after surgery and how intensive it should be. A positive result may support using or continuing chemotherapy or closer follow‑up, while a negative result may, in some situations, support shorter or less intensive treatment—always together with other clinical information and guidelines.
How often is MRD testing done?
MRD testing can be done on a regular schedule—such as monthly, every few months, or at key time points after treatment—depending on your situation and your oncologist’s recommendations. The goal is to give you and your doctor a clearer picture of your cancer status between scans.
Does a positive MRD result mean my cancer will definitely come back?
A positive MRD result suggests that cancer DNA is present and that there may be a higher risk of recurrence, but it does not guarantee what will happen in the future. Your doctor may recommend closer monitoring, additional tests, or changes to your treatment plan based on this result.
Does a negative MRD result mean I am “cancer-free”?
A negative MRD result means the test did not detect colorectal tumor DNA above its limit of detection at that time. This is encouraging and generally linked with a lower risk of recurrence, but no test is perfect. Results can change, so you will still need regular follow‑up visits, labs, and scans.
Can MRD testing reduce “scanxiety” or worry about recurrence?
Many people with colorectal cancer say MRD testing provides another layer of information between scans, which can offer peace of mind when results are negative. For others, an early positive result may be stressful but also gives more time to plan next steps with their care team. It is important to talk openly with your doctor about how often to test and how you prefer to receive results.
Is MRD testing a replacement for regular follow-up care?
No. MRD testing is meant to complement—not replace—your regular follow-up visits, scans, blood work, and physical exams. It is one more tool your team can use to personalize your care and help you stay as informed and proactive as possible.
This FAQ is for general education and is not a substitute for medical advice. Always discuss your specific situation and test results with your oncology team.
When do patients with colorectal cancer usually get MRD testing?
Your doctor may consider ctDNA/MRD testing: after surgery to see if there is any remaining cancer DNA, during or after chemotherapy to track how well treatment is working, and during regular follow‑up visits to watch for signs of recurrence. Testing is often done repeatedly over time (for example, every few months) as part of ongoing surveillance.
Is MRD testing used only for early‑stage colorectal cancer?
Most current use and research focuses on stage II and III colorectal cancer, and some resected stage IV disease in cases where patients have had surgery with curative intent. In certain advanced or metastatic cases, ctDNA/MRD testing may also be used to help track how well treatment is working and to look for early signs of progression.
Will my insurance cover MRD testing for colorectal cancer?
Coverage can depend on your diagnosis, stage, and insurance plan. Medicare currently covers certain ctDNA/MRD tests, such as Signatera, for monitoring recurrence in colorectal cancer, and many commercial plans may also provide coverage in specific situations. Your oncology team or the testing company can help check your benefits and any out‑of‑pocket costs before testing is done.
What is the difference between a “tumor-informed” MRD test and a blood-based ctDNA test?
A “tumor-informed” MRD test and a blood-based ctDNA test are both blood tests that look for evidence of cancer in the bloodstream, but they are designed and used a bit differently.
In a tumor-informed MRD test, the lab starts by analyzing a sample of your tumor tissue (for example, from surgery or a biopsy). They look for the specific DNA changes (mutations) that are unique to your cancer. Then they create a personalized blood test that checks your blood for those exact changes over time. Because it is tailored to your tumor, this type of test can be very sensitive for finding very low levels of remaining cancer after treatment and for monitoring whether cancer might be coming back.
In a more general blood-based MRD test (sometimes called “tumor-naive” or “tumor-agnostic”), the lab does not need your tumor tissue first. Instead, the test looks in your blood for a panel of common cancer-related changes to the DNA. This can be useful when tumor tissue is hard to get or unavailable, but it may be less personalized than a tumor-informed test.
In simple terms:
- Tumor-informed MRD test = built “from your tumor up,” customized to your cancer, mainly used to look for minimal residual disease and recurrence.
- Blood-based MRD test = uses a standard panel to look for cancer-specific changes to the DNA in blood, without first studying your tumor, and may be used for diagnosis, treatment selection, or monitoring, depending on the test.
Your oncology team can explain which test they are using, why it was chosen, and how to interpret the results in your specific situation.
How do I talk to my doctor about MRD testing?
You can start by asking:
- “Is MRD testing appropriate for me?”
- “What would we do differently based on a positive or negative result?”
- “How often would you recommend testing, and for how long?”
Your doctor can explain the benefits, limitations, and whether a personalized MRD test fits into your overall care plan.
Online support: Join the conversation on CancerConnect
More Reading
Ask the Experts about ctDNA in the Management of Colorectal Cancer
Biomarkers: How Your Cancer’s Unique “Fingerprint” Can Guide Treatment
Advances in Genomic Testing- What You Need to Know
What is Precision Cancer Medicine?
FAQs: NGS-Genomic Testing and Cancer Care
This educational resource was made possible by Natera, OmniOncology, and The Personalized Medicine Foundation.
References
Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol. 2018;36(16):1631‑1641.
Reinert T, Henriksen TV, Christensen E, et al. Analysis of plasma cell‑free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5(8):1124‑1131.
Tie J, Cohen JD, Lahouel K, et al. Circulating tumor DNA analyses as markers of recurrence risk and benefit of adjuvant therapy for stage III colon cancer. JAMA Oncol. 2019;5(12):1710‑1717.
Parikh AR, Van Seventer EE, Siravegna G, et al. Minimal residual disease detection using a plasma‑only circulating tumor DNA assay in colorectal cancer. Clin Cancer Res. 2021;27(20):5586‑5594.
