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CPT 81464: Plasma Liquid Biopsy Genomic Sequencing for Solid Tumors
CPT code 81464 represents a comprehensive plasma-based genomic sequencing assay (liquid biopsy) that identifies cell–free DNA and DNA/RNA alterations relevant to solid organ cancers, and reports additional biomarkers such as microsatellite instability (MSI) and tumor mutation burden (TMB). This code captures advanced molecular profiling used to inform targeted therapy selection, monitor tumor genomics noninvasively, and support precision oncology workflows. Nationally, plasma-based genomic testing is increasingly integrated into oncology care pathways as an alternative or complement to tissue-based profiling, with implications for access, turnaround time, and care coordination.
Key payers in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. The publication summarizes payer coverage patterns, coding and billing considerations, and how CPT code 81464 maps to clinical use cases in solid tumor management.
Readers will learn the clinical scope of CPT code 81464, typical sites of service and service type, common clinical indications for ordering this test, and how the code relates to other genomic sequencing and proprietary laboratory codes in the same clinical group. The report also provides benchmarks and policy updates relevant to coverage and utilization of plasma-based genomic sequencing for somatic alterations, along with operational considerations for laboratories and oncology providers.
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Billing Code Overview
CPT code 81464 describes a liquid biopsy genomic sequencing test performed on a plasma specimen to analyze cell–free DNA (cfDNA) or DNA/RNA. The analysis includes detection of nucleic acid sequence variants, copy number variants, and rearrangements that are relevant to solid organ neoplasms, and assesses biomarkers that may guide treatment such as microsatellite instability (MSI) and tumor mutation burden (TMB).
Service Type: Genomic sequencing for somatic alterations using a plasma (liquid biopsy) specimen
Typical Site of Service: Clinical laboratory or outpatient phlebotomy/collection site
National Reimbursement Benchmarks
National commercial reimbursement for CPT 81464 centers near the BUCA average commercial rate of $2,688.90, with notable differences across major carriers. Blue Cross Blue Shield shows the highest dispersion between its 25th and 75th percentiles ($1,717.70), indicating wide variability in negotiated rates; Cigna and Aetna have moderate spreads of $2,144.40 and $1,097.00 respectively. UnitedHealth Group’s interquartile spread is $1,907.30, also reflecting substantial variability, while BUCA’s IQR is $1,717.00 and thus aligns closely with Blue Cross Blue Shield in dispersion.
Looking at central tendency, Cigna’s median ($2,946.50) and Blue Cross Blue Shield’s median ($2,572.30) sit above the BUCA mean, while UnitedHealth Group’s median ($1,973.10) falls below. Minimum-to-maximum ranges exist for Aetna, Blue Cross Blue Shield, Cigna, and UnitedHealth Group per the provided values, underscoring that list extremes can differ markedly even when averages cluster near the BUCA commercial benchmark of $2,688.90.