Medicare Expands Coverage of Signatera MRD Testing for Hepatocellular Carcinoma Surveillance
Clinical Summary:
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Coverage Update: Medicare coverage has been extended to serial Signatera molecular residual disease (MRD) testing for surveillance of patients with early-stage hepatocellular carcinoma who have no evidence of disease following surgery.
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Key Outcomes: The decision was supported by a real-world study of 125 patients with hepatocellular carcinoma, in which Signatera demonstrated 83% sensitivity and 100% specificity, compared with 42% sensitivity for alpha-fetoprotein. Signatera detected molecular recurrence a median of 7.9 months before imaging, with a maximum lead time of 16.5 months.
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Clinical Relevance: This coverage expansion increases access to personalized MRD testing for postoperative hepatocellular carcinoma surveillance, potentially improving early recurrence detection and complementing conventional imaging and alpha-fetoprotein monitoring.
Medicare coverage has been extended to serial Signatera molecular residual disease (MRD) testing for surveillance of patients with early-stage hepatocellular carcinoma who have no evidence of disease following surgery, expanding access to personalized testing for postoperative recurrence monitoring.
The coverage decision was issued through the Centers for Medicare & Medicaid Services Molecular Diagnostics Services Program and includes serial Signatera testing in the surveillance setting.
The decision was supported by findings from a real-world study of 125 patients with hepatocellular carcinoma published in JCO Precision Oncology, which demonstrated greater sensitivity for recurrence detection with Signatera compared with alpha-fetoprotein, a guideline-recommended biomarker used in conventional hepatocellular carcinoma surveillance.
In this study, Signatera demonstrated a sensitivity of 83% compared with 42% for alpha-fetoprotein, with a reported specificity of 100%.
Signatera also identified molecular evidence of recurrence ahead of conventional imaging, with a median lead time of 7.9 months and a maximum lead time of 16.5 months. In comparison, the reported lead time for alpha-fetoprotein was 2.2 months.
These findings suggest that tumor-informed ctDNA testing may provide additional information for detecting recurrence following treatment for hepatocellular carcinoma, particularly when conventional surveillance methods yield inconclusive findings.
“Conventional surveillance tools can miss early signs of relapse in hepatocellular carcinoma...imaging after liver surgery or transplant is often hard to interpret, and alpha-fetoprotein misses many recurrences," stated Maen Abdelrahim, MD, PhD, Houston Methodist Cancer Center, Houston Texas. "Signatera gave us a signal months earlier, and in our study, it helped clarify ambiguous scans."
The coverage expansion applies specifically to patients with early-stage hepatocellular carcinoma who have no postsurgical evidence of disease and are undergoing surveillance. It does not establish coverage for all patients with hepatocellular carcinoma or for testing in other disease settings.
The findings support the potential role of serial MRD testing as a complementary surveillance tool following surgery for early-stage hepatocellular carcinoma, although the announcement does not establish whether earlier molecular detection improves survival or other long-term clinical outcomes.
The Medicare coverage decision expands access to Signatera for eligible patients with hepatocellular carcinoma, providing an additional option for postoperative recurrence monitoring alongside established surveillance approaches.
Source:
Natera. Medicare expands coverage for Signatera™ MRD test in hepatocellular carcinoma. Accessed on: November 3, 2026. https://www.natera.com/company/news/medicare-expands-coverage-for-signatera-mrd-test-in-hepatocellular-carcinoma
