When is the Signatera (circulating tumor DNA) test used in patients with a history of solid tumors, such as colorectal, breast, or lung cancer?

When Signatera ctDNA Testing is Used

Signatera is a tumor-informed, personalized ctDNA assay used primarily for postoperative surveillance to detect molecular residual disease and predict recurrence ahead of clinical or radiologic findings in patients with solid tumors, particularly colorectal, breast, and lung cancers. 1, 2

Primary Clinical Applications

Postoperative Surveillance and Recurrence Detection

• Signatera detects molecular relapse with high sensitivity (88.2% in breast cancer) up to 38 months before clinical or radiologic evidence of recurrence (median lead time: 10.5 months). 1
• The test is performed serially on blood samples collected at regular intervals (typically every 3-6 months) after definitive surgical resection and completion of adjuvant therapy. 1, 2
• ctDNA positivity strongly predicts shorter relapse-free survival and overall survival, providing critical prognostic information that current clinical tests like CA 15-3 cannot match. 1

Monitoring Treatment Response

• Signatera quantifies tumor burden during active treatment by measuring tumor-specific mutations in plasma, with ctDNA levels correlating directly with disease burden. 3, 4
• The assay is particularly valuable for monitoring response to targeted therapies and immunotherapy, where early molecular response can guide treatment decisions. 5, 4
• Serial ctDNA measurements can identify treatment failure earlier than imaging, allowing for timely therapeutic adjustments. 3, 4

Tumor-Specific Considerations

Breast Cancer

• All relapsing triple-negative breast cancer patients (100%) had ctDNA-positive tests within a median of 8 months before clinical relapse, while non-relapsed patients remained ctDNA-negative during median 58-month follow-up. 1
• Hormone receptor-positive (HR+) disease shows occasional false-positive results, requiring serial monitoring rather than single-test decision-making. 1
• Serially negative ctDNA tests provide strong reassurance of superior clinical outcomes in breast cancer patients. 1

Colorectal Cancer

• Signatera effectively characterizes recurrence sites after optimal resection of metastatic colorectal cancer, with detection preceding clinical diagnosis by median 9 weeks. 2
• Peritoneal-only recurrence shows delayed ctDNA detection (75% negative at 3 months) and lower ctDNA levels compared to distant metastases (94.4% positive at 3 months). 2
• ctDNA was detected in all patients (100%) who experienced postoperative recurrence and remained undetectable in those without recurrence. 2

Lung Cancer

• While Signatera can be used in non-small cell lung cancer, the European Society for Medical Oncology and American Society of Clinical Oncology recommend ctDNA testing primarily for EGFR mutation detection when tissue is unavailable, rather than for routine surveillance. 6, 7
• Approximately 25% of NSCLC patients are "non-shedders" with DNA levels below detection limits, making negative results unreliable in this population. 6, 7

Critical Limitations and Interpretation Pitfalls

Technical Considerations

• Signatera is a tumor-informed assay requiring whole-exome sequencing of the primary tumor tissue to create a personalized panel, which increases sensitivity and accuracy but also cost and complexity. 7, 1
• The test must be performed in CLIA-certified laboratories with clinical validation to ensure reliability for clinical decision-making. 6, 7

Clinical Interpretation Challenges

• Negative ctDNA results do not exclude the presence of disease, particularly in early-stage disease, low tumor burden, or in "non-shedder" patients. 6, 7
• Detection sensitivity varies by cancer stage, tumor burden, proximity of sampling site to disease, and biomarker type. 7
• In HR+ breast cancer, occasional positive tests may occur without subsequent clinical relapse, requiring serial monitoring and clinical correlation rather than immediate treatment escalation. 1

Optimal Clinical Integration Strategy

When to Order Signatera

• After optimal surgical resection of primary solid tumors (particularly colorectal and breast cancer) when the goal is early detection of molecular residual disease. 1, 2
• Following completion of adjuvant therapy to establish a baseline and monitor for recurrence during surveillance. 1
• When characterizing recurrence patterns after metastatic disease resection to guide site-specific treatment strategies. 2

When NOT to Use Signatera

• Do not use for initial cancer screening or diagnosis - tissue biopsy remains the gold standard for histological diagnosis and comprehensive molecular profiling. 6, 7
• Avoid using as the sole basis for treatment decisions in HR+ breast cancer without serial confirmation. 1
• Do not rely on negative results to exclude disease, especially in NSCLC where non-shedders are common. 6, 7

Monitoring Schedule

• Perform serial testing every 3-6 months during the first 2-3 years post-treatment when recurrence risk is highest. 1
• Continue surveillance longer in triple-negative breast cancer given 100% sensitivity for detecting recurrence. 1
• Adjust frequency based on cancer type, stage, and individual risk factors. 1, 2