OBJECTIVES: Liquid biopsy-based testing approaches, including next generation sequencing (NGS) of circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) testing, are increasingly important and powerful tools enabling precision oncology care, particularly when biopsy tissue/ DNA is limiting in cancers with multiple associated biomarkers (e.g., lung cancer), potential for significant heterogeneity across metastases exists, and/or rapid, non-invasive assessment of cancer progression/ monitoring is needed. Given the growing evidence base for liquid biopsy-based testing, we evaluated the payer coverage and clinical guideline landscape for oncology liquid biopsy-based testing in the United States to understand current coverage status, and evidence gaps to fill for expanding coverage and inclusion of liquid biopsy-based testing in cancer guidelines.

METHODS: We reviewed clinical guidelines, and coverage policies across more than 50 national and regional commercial health plans, and Medicare relevant to liquid biopsy-based testing in oncology for coverage status and evidence-based rationale.

RESULTS: Despite an increasing number of recent studies demonstrating utility of liquid biopsy-based testing, only a small minority of health plans covered such testing. Where liquid biopsy testing was covered, coverage was limited to specific branded ctDNA multigene panel test platforms, and a subset of policies further limited ctDNA testing to small, targeted panel or single-gene testing only. Collectively, clinical guidelines and payer policies that excluded liquid biopsy-based testing suggested a lack of evidence from well-designed, sufficiently-powered, peer-reviewed studies in specific cancer types demonstrating accuracy/ concordance with tissue biopsy-based panel testing, appropriate timing for test conduct, cutoff thresholds for considering test results positive, impact on patient management/ guiding treatment decisions, and impact on patient outcomes and healthcare resource utilization.

CONCLUSIONS: While only a small number of health plans covered liquid biopsy-based testing in oncology, our research suggests opportunity to target a well-defined, and addressable set of evidence gaps to support expanding payer coverage and clinical guideline inclusion.