MRD Signatera: A Personalized Molecular Residual Disease Detection Test
Signatera is a personalized, tumor-informed molecular residual disease (MRD) detection test that uses circulating tumor DNA (ctDNA) to monitor cancer recurrence with high sensitivity and specificity. 1, 2
What is MRD?
MRD (Measurable Residual Disease) refers to the presence of cancer cells that remain in the body during or after treatment at levels below what conventional imaging or laboratory tests can detect. Key aspects include:
- MRD represents the persistence of tumor cells that could potentially lead to clinical progression or relapse 3
- The term "Measurable" is preferred over "Minimal" as it is more objective when the detection limit is specified 3
- MRD detection is critical because patients who achieve complete response by morphologic assessment alone can potentially harbor significant numbers of residual cancer cells 3
How Signatera Works
Signatera is a ctDNA-based MRD detection test with the following characteristics:
- Uses next-generation sequencing (NGS) to analyze cell-free DNA fragments in blood that originate from tumor cells 1, 4
- Creates a personalized, tumor-informed assay based on the patient's unique tumor mutation profile 2, 5
- Provides highly sensitive detection of residual disease, often at levels below what conventional imaging can identify 4, 6
- Can detect MRD at sensitivity thresholds of <1×10⁻⁶ (<0.0001%) in some cases 3, 5
Clinical Applications of MRD Signatera
Signatera has several important clinical applications:
- Early Recurrence Detection: Identifies molecular recurrence months before conventional imaging shows evidence of disease 2, 4
- Treatment Response Monitoring: Evaluates treatment efficacy in real-time through serial measurements 1, 5
- Risk Stratification: Helps identify patients at higher risk of recurrence who may benefit from additional treatment 4, 6
- Adjuvant Therapy Guidance: Supports decisions about adjuvant therapy based on MRD status 5, 6
Reporting and Interpretation
MRD reporting follows standardized nomenclature:
- Results typically indicate whether disease is detectable or undetectable at a specified threshold 3
- Reports include the detection limit of the sample, which depends on the assay used and sample quality 3
- Categorical measures may be used to indicate the upper limit of MRD (e.g., MRD4 for <10⁻⁴ or <0.01% disease) 3
- "Undetectable-MRD" (U-MRD) is preferred over "MRD-negative" as disease may be present below the reporting threshold 3
Advantages of Signatera Over Other MRD Tests
- Personalization: Tailored to each patient's unique tumor mutation profile 2, 5
- High Specificity: Minimizes false positives by focusing on tumor-specific mutations 2, 6
- Non-invasive: Requires only a blood sample, allowing for frequent monitoring 1, 4
- Dynamic Monitoring: Can track changes in MRD status over time to guide treatment decisions 5, 6
Limitations and Considerations
- Sensitivity may be affected by tumor shedding characteristics and timing of sample collection 5
- False negatives can occur if the tumor doesn't shed sufficient DNA into circulation 5
- Standardization of testing and interpretation protocols is still evolving 5
- Clinical validation in large prospective trials is ongoing for many cancer types 2, 6
Current Applications by Cancer Type
Signatera has been studied in various solid tumors including: