Early cancer detection and effective therapy are crucial for improving survival rates among cancer patients.¹ Scientists have known for decades that tumors shed cells and molecules into body fluids such as blood and more recently have learned that analyzing these cells can reveal information that traditional invasive tissue biopsies have historically provided.² This process, referred to as liquid biopsy, is changing the cancer diagnosis and treatment monitoring paradigm.³ Unlike traditional tissue biopsies obtained directly from the tumor, which have historically been the gold standard, liquid biopsies provide a less invasive way to detect cancer and monitor treatment.¹˒²

Liquid biopsy is being utilized throughout the entire cancer continuum and can be divided into three general clinical applications including cancer early detection, treatment decision making and post-treatment monitoring through minimal residual disease (MRD) detection.⁴ Multicancer early detection (MCED) testing utilizes blood to screen for multiple types of cancers aiming to detect cancer before it can be identified using current available techniques such as colonoscopy and mammography.⁵˒⁶˒⁷ During initial cancer diagnosis or with progression, liquid biopsy can be complementary to a tissue biopsy by helping to detect genetic information and tumor mutations that might not be visible in the tissue sample allowing for the use of more effective targeted therapies that improve outcomes.¹ As cancer treatment is ongoing, liquid biopsy can enable repeated, less invasive real-time monitoring to provide insight into how a patient’s cancer is changing; this can help inform a decision to escalate or de-escalate therapy.⁴˒⁸ Following a complete response or remission, liquid biopsy can help detect early signs of cancer recurrence.⁹

One of the most promising applications to date is detection of MRD. Minimal residual disease can be detected via bone marrow aspiration or via liquid biopsy to detect trace amounts of cancer cells after treatment.¹⁰˒¹¹˒¹² The FDA has approved the use of MRD via bone marrow or blood in hematologic cancers including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). In April 2024, the FDA Oncologic Drugs Advisory Committee (ODAC) endorsed the use of MRD as a surrogate endpoint for accelerated drug approval in multiple myeloma. This pivotal decision enables earlier approval and access to new therapies based on MRD negativity rates.¹³ While still less common in solid tumors, the use of MRD is burgeoning.⁴  

There are several challenges to widespread clinical adoption of liquid biopsy including uncertainty around performance and reliability of testing, lack of knowledge among providers and cost. Payer coverage for liquid biopsy testing remains inconsistent across the United States.⁴ The Centers for Medicare & Medicaid Services (CMS) established the Molecular Diagnostic Services (MolDx) Program in 2011 to evaluate molecular test coverage and reimbursement, but it wasn’t until 2020 that liquid biopsy tests were formally included. CMS now covers MRD testing for B-cell ALL, CLL and MM, with expanding coverage for liquid biopsy in advanced solid tumors for genomic profiling, therapy selection and recurrence monitoring.¹⁴ Commercial coverage varies widely with MRD testing generally covered for select cancers aligned with the National Comprehensive Cancer Network (NCCN) guidelines. Liquid biopsy is more narrowly covered—typically for identifying actionable mutations when tissue biopsy isn’t feasible.¹⁴ To ensure cost-effective use of resources, payers must continuously monitor emerging evidence comparing liquid and tissue biopsy, as the optimal use of one, the other, or both may vary depending on cancer type, stage, and clinical context. Coverage for early detection and early-stage cancers remains limited across CMS and commercial payers due to evolving clinical data but changes may be coming.⁴˒¹⁵ Legislation for CMS coverage of MCED testing was introduced in early 2025.¹⁶

Despite these barriers, the integration of liquid biopsy into clinical practice holds considerable potential for significant cost savings. It can reduce expenditures for health plans and providers by enabling earlier cancer detection and minimizing the need for costly invasive procedures, highlighting its potential economic value as clinical evidence supporting its use continues to grow.¹⁶