Which of the following statements about MRD results is incorrect?

• A. The presence of ctDNA directly indicates residual disease.
• B. Precise MRD results are reported as ctDNA detected or ctDNA not detected.
• C. MRD results are sometimes used to guide treatment decisions.
• D. A negative MRD result definitively rules out recurrence.

Answer: (D)

Understanding MRD results hinges on how ctDNA testing works and its limits. A detectable ctDNA signal means tumor-derived DNA is present in the blood, providing clear evidence of residual disease. In many settings, MRD results are reported simply as ctDNA detected or ctDNA not detected, and these results can be used to guide treatment decisions by signaling ongoing disease activity that might warrant a change in management or closer monitoring.

However, a negative MRD result does not definitively rule out recurrence. The assay has a limit of detection, so very small amounts of tumor DNA or intermittent shedding can fall below the threshold even when disease remains. Tumors at certain sites or with low ctDNA release may not be captured in a blood test, and relapse can occur later when ctDNA levels rise again. Therefore, while a positive ctDNA result strongly indicates residual disease, a negative result cannot guarantee that recurrence will not happen.