Medically Reviewed by: Charles H. Weaver, MD
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.
What is ctDNA and MRD testing in bladder cancer?
Minimal or molecular residual disease (MRD) is the term doctors use when a very small amount of bladder cancer remains after treatment—too little to be seen on scans or cystoscopy, but still important to detect. Circulating tumor DNA (ctDNA) refers to tiny fragments of bladder cancer DNA that are released into the bloodstream by the cancer cells. ctDNA‑based MRD testing is a blood test designed to pick up these traces of tumor DNA, which can be a sign that bladder cancer is still present in the body and is likely to recur even when imaging and cystoscopy look normal.
How is MRD testing different from regular scans, cystoscopy, or blood tests?
Imaging tests (like CT, MRI, or PET scans) show cancer only when the cancer is large enough to detect by imaging, and cystoscopy looks directly inside the bladder but cannot see cancer that has already spread elsewhere in the body. MRD testing can sometimes detect bladder cancer DNA weeks, months, or even years before anything appears on scans or cystoscopy. Standard blood and urine tests may look at general markers, but MRD tests are designed to detect DNA changes that are specific to your bladder cancer.
How does MRD testing work?
Most MRD tests used in bladder cancer are “personalized” or “tumor‑informed.” They start with a sample of your bladder tumor (for example, from a TURBT procedure, partial cystectomy, or radical cystectomy) to identify its unique DNA changes. A custom blood test is then created, and future blood draws are checked for those same DNA changes to see whether bladder cancer DNA is still present in your bloodstream.
Who might benefit from MRD testing in bladder cancer?
MRD testing may be helpful if you have muscle‑invasive bladder cancer and have had surgery to remove the bladder or other treatment with curative intent, if your cancer has come back before, or if you and your doctor want closer monitoring between scans and cystoscopies. Importantly, recent data support the potential role of tumor‑informed ctDNA testing as a tool to guide response‑adapted, bladder‑sparing treatment decisions in MIBC following neoadjuvant treatment. In addition, it may also be useful for people at higher risk of recurrence—for example, those with more advanced stage disease or high‑risk features on their pathology report.
What can MRD test results show?
MRD results generally fall into two main categories:
- MRD negative: No bladder cancer DNA is detected in your blood above the test’s limit at that time, which can be a reassuring sign and is linked in studies to a lower risk of recurrence and improved prognosis.
- MRD positive: Bladder cancer DNA is found in your blood, which typically means cancer is still present or starting to return, even if scans and cystoscopy look normal.
Your doctor will interpret these results in the context of your bladder cancer stage, pathology, treatment history, and other tests.
How can MRD testing help guide treatment decisions?
MRD results can help your care team:
- Determine initial prognosis
- Guide response‑adapted, bladder‑sparing treatment decisions in MIBC
- Detect possible recurrence earlier and consider starting treatment sooner
- Track how well chemotherapy, immunotherapy, or other systemic treatments are working
- Decide whether to continue, change, or stop certain therapies, especially if MRD stays positive or becomes negative; and, in some situations, avoid unnecessary or prolonged treatment if MRD remains negative, which may reduce side effects and improve quality of life.
How often is MRD testing done in bladder cancer?
MRD testing can be done on a regular schedule—such as every 2-3 months after surgery or during and after systemic treatment—depending on your situation and your oncologist’s recommendations. The goal is to give you and your doctor a clearer, more continuous picture of your bladder cancer status between scans and cystoscopies.
Does a positive MRD result mean bladder cancer will definitely come back?
A positive MRD result suggests that bladder cancer DNA is present and that there is a higher risk of recurrence, but it does not guarantee that visible cancer will return or when this might happen. Your doctor may recommend closer monitoring, additional imaging, or changes to your treatment plan based on this result and your overall risk factors.
Does a negative MRD result mean I am “cancer‑free”?
A negative MRD result means the test did not detect bladder cancer DNA above its limit of detection at that time. This is encouraging, but no test is perfect, so you will still be monitored.
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. 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.
With a more general blood-based MRD test (sometimes called “tumor-naive” or “tumor-agnostic”), the lab does not use your tumor tissue to create a personalized test. 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 unavailable, but it is less sensitive and specific 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.
Your oncology team can explain which test they are using, why it was chosen, and how to interpret the results in your specific situation.
When is ctDNA‑based MRD testing usually considered in bladder cancer?
Doctors best utilize ctDNA‑based MRD testing when obtained at the time of initial diagnosis. This helps determine prognosis, allows them to monitor response to treatment and check for any remaining cancer cells that are too small to see on imaging. Testing is typically performed at regular intervals during follow‑up visits to look for early signs of recurrence or to track how well systemic treatments (like chemotherapy, targeted therapy, or immunotherapy) are working. Recent data support the potential role of tumor‑informed ctDNA testing as a tool to guide response‑adapted, bladder‑sparing treatment decisions in MIBC following neoadjuvant treatment.
Can MRD/ctDNA testing help determine if bladder sparing approach are appropriate for me?
Recent research indicates that ctDNA testing may help identify which people with muscle‑invasive bladder cancer (MIBC) can safely keep their bladder after neoadjuvant treatment while maintaining good cancer outcomes. Updated results from two multicenter phase 2 trials, INDIBLADE and RETAIN, showed that ctDNA “clearance” or sustained ctDNA‑negativity after neoadjuvant therapy was strongly associated with better survival outcomes, even when patients were managed with bladder‑sparing strategies instead of immediate cystectomy.
Can MRD/ctDNA testing help decide if I need immunotherapy or chemotherapy after bladder surgery?
Studies suggest that patients with detectable ctDNA after surgery are at higher risk for their bladder cancer returning and may benefit more from additional treatments such as immunotherapy. If ctDNA is not detected, some patients may be safely followed with surveillance alone, potentially avoiding extra treatment and side effects, though decisions are always individualized.
Can MRD testing reduce “scanxiety” or worry about recurrence?
Many people with bladder cancer say MRD testing provides another layer of information between scans and procedures, which can offer peace of mind when results are negative. For others, an early positive result may feel stressful but also allows more time to act and plan next steps with their care team. It is important to discuss how often to test and how you prefer to receive results.
Are MRD tests available for all types and stages of bladder cancer?
Tumor‑informed MRD tests are being actively studied and increasingly used in muscle‑invasive bladder cancer and in people who have had the bladder removed, but availability and insurance coverage can vary by stage, treatment setting, location, and health plan. Your oncologist can tell you whether a personalized MRD test is appropriate and accessible for your specific diagnosis, including if you have non–muscle‑invasive or metastatic disease.
How do I talk to my doctor about MRD testing for bladder cancer?
You can start by asking:
- Is MRD or ctDNA testing available and appropriate for me?
- Would ctDNA testing help inform whether bladder sparing approaches are 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, current evidence in bladder cancer, and whether a personalized MRD test fits into your overall care plan.
Is MRD testing a replacement for regular bladder cancer follow‑up care?
No. MRD testing is meant to complement—not replace—your regular follow‑up visits, cystoscopy, urine tests, scans, and physical exams. It is one more tool your team can use to personalize your bladder cancer 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 urologist and oncology team.
What does it mean if my MRD result is “below the limit of detection” or the sample is “inadequate”?
Sometimes an MRD report will say that the amount of tumor DNA in your blood is below the test’s “limit of detection.” This means the test could not reliably measure any cancer DNA at or above the level it is designed to detect at that time. In many cases, this is treated similarly to a negative result and can be reassuring, but it does not prove with 100% certainty that there is no cancer anywhere in the body, so your doctor will still recommend routine follow‑up visits, labs, and scans.
In other situations, the report may say the sample was “inadequate” or “insufficient.” This usually means there was not enough usable DNA in the blood tube, the sample was delayed or mishandled in transit, or there was a technical issue in the lab that prevented a reliable result. An inadequate sample does not tell you anything about whether cancer is present or not. In that case, your care team may recommend repeating the blood draw, waiting until a better time (for example, when your blood counts have recovered), or relying on other tests and scans while deciding whether to try MRD testing again.
These FAQs are general information and not a substitute for medical advice. Always talk with your urologist or oncologist about how MRD/ctDNA testing may or may not fit into your personal bladder cancer care plan.
Online support: Join the conversation on CancerConnect
More Reading
ctDNA Testing May Help More Patients Preserve Their Bladder
Personalized ctDNA MRD Testing Improves Outcomes in Muscle-Invasive Bladder Cancer
Signatera-Guided Immunotherapy Improves Survival in Bladder 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
| Other Resources: Natera Facing Recurrence Again? How MRD Testing Can Support You Every Step of the Way Signatera Results Patient Guide How to Prepare for Your Next MRD Test: Practical Tips and FAQs |
This educational resource was made possible by Natera, OmniOncology, and The Personalized Medicine Foundation.
References
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Ghatalia P, Ross EA, Zibelman MR, et al. Circulating tumor DNA (ctDNA) to guide response-adapted bladder preservation in muscle invasive bladder cancer (MIBC): Integrated analysis of the RETAIN trials. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA632. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16924
