Summary & Overview

CPT 0498U: OptiSeq™ Colorectal Cancer NGS and Methylation Panel

Headline: New PLA CPT code 0498U designates the OptiSeq™ Colorectal Cancer NGS Panel, a proprietary next-generation sequencing (NGS) and methylation assay for colorectal cancer.

Lead: CPT code 0498U uniquely identifies the OptiSeq™ Colorectal Cancer NGS Panel from DiaCarta Inc., a combined mutation and methylation assay that analyzes 43 genes for sequence variants and 45 genes for methylation patterns using blood and FFPE tissue. The code clarifies billing for a single-manufacturer laboratory test that provides diagnostic and interpretive data to guide colorectal cancer care.

Why it matters: Proprietary Laboratory Analyses (PLA) codes like 0498U standardize reporting for single-source tests and affect claims adjudication, coverage determinations, and utilization tracking nationwide. Clear identification supports payer policy alignment and enables consistent reference in clinical and administrative workflows.

Key payers covered: Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare.

What readers will learn: The publication summarizes the clinical scope of CPT code 0498U, expected sites of service and specimen types, payer coverage landscape, common billing modifiers, and implications for coding and documentation. It provides benchmarks and policy context relevant to laboratory stakeholders, oncology practices, and billing teams. Data not available in the input will be noted where applicable.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0498UCPTProprietary Laboratory AnalysisNext-Generation SequencingColorectal CancerMethylation PanelLaboratory MedicineGenetic Testing

Billing Code Overview

CPT code 0498U is a Proprietary Laboratory Analyses (PLA) code that applies exclusively to the OptiSeq™ Colorectal Cancer NGS Panel from DiaCarta Inc. The test uses next-generation sequencing to analyze mutations in 43 genes and methylation patterns in 45 genes from blood and formalin–fixed paraffin–embedded (FFPE) tissue samples. The service produces a detailed report with interpretation of genetic variants and methylation patterns relevant to colorectal cancer.

Service type: Next-generation sequencing (NGS) tumor and circulating biomarker panel with methylation analysis

Typical site of service: Clinical laboratory processing with specimen collection from outpatient clinics, hospital pathology suites, or specialized oncology centers; samples include blood and FFPE tissue

Clinical & Coding Specifications

Clinical Context

A typical patient is a 62-year-old individual with a history of colorectal adenocarcinoma who presents for molecular profiling to guide targeted therapy and prognosis. The oncologist orders the OptiSeq™ Colorectal Cancer NGS Panel (0498U) after reviewing prior pathology showing invasive colorectal carcinoma on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Peripheral blood is also collected for circulating tumor DNA (ctDNA) analysis when tumor tissue is limited or to assess minimal residual disease. The laboratory receives the FFPE tissue block or unstained slides and/or a plasma specimen, performs DNA extraction, next-generation sequencing (NGS) targeting 43 genes for somatic mutations and assays methylation patterns across 45 genes, and generates a comprehensive report with variant interpretation, allele frequencies, and methylation results. The clinical workflow includes specimen collection, chain-of-custody documentation, molecular testing under CLIA-certified procedures, analytic validation, pathologist or molecular geneticist review of reportable variants, and electronic delivery of results to the ordering oncologist. Typical clinical uses include selection of targeted therapies, enrollment decisions for clinical trials, prognostic assessment, and monitoring for recurrence using ctDNA when applicable.

Coding Specifications

Modifier	Description	When to Use
`00`	Standard/Not otherwise specified modifier placeholder (per input list)	Use when no additional modifier applies; report `0498U` without special circumstance modifier when standard testing performed.
`22`	Increased procedural services	Use when additional work, such as substantially greater technical or interpretive effort, is documented (e.g., complex repeat testing, extensive microdissection of FFPE tissue).
`52`	Reduced services	Use when the test is partially reduced or an abbreviated panel is performed and documentation supports a reduced service.
`53`	Discontinued procedure	Use when testing was initiated but discontinued for documented reasons (e.g., inadequate specimen) prior to completion.

Taxonomy Code	Specialty	Notes
`207RG0100X`	Hematology & Oncology	Medical oncologists commonly order tumor genomic profiling for targeted therapy selection.
`207RH0000X`	Medical Oncology	Oncology subspecialists managing colorectal cancer care order and interpret NGS reports.
`2085P0207X`	Pathology	Surgical pathologists oversee tissue processing, microdissection, and specimen adequacy assessment.
`363L00000X`	Clinical Laboratory	Clinical molecular/pathology laboratories perform the NGS assay under CLIA certification.
`207K00000X`	Gastroenterology	Gastroenterologists may order testing at diagnosis or for recurrence evaluation.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C18.9`	Malignant neoplasm of colon, unspecified	Common indication for colorectal cancer molecular profiling to guide therapy and prognostic assessment.
`C20`	Malignant neoplasm of rectum	Rectal cancers benefit from NGS profiling for actionable mutations and potential targeted therapies.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Used when testing is performed for surveillance or recurrence risk assessment in a patient with prior colorectal cancer.
`C78.7`	Secondary malignant neoplasm of liver and intrahepatic bile duct	When metastatic disease is present, tumor profiling from metastasis or blood can inform systemic therapy.
`R97.2`	Elevated carcinoembryonic antigen [CEA]	Rising tumor marker prompting molecular testing for recurrence or residual disease evaluation.
`Z15.09`	Genetic susceptibility to other malignant neoplasm	When germline risk or family history prompts targeted methylation or mutation assessment as part of broader evaluation.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81479`	Unlisted molecular pathology procedure	Used when a specific proprietary PLA code is not available; for `0498U` the PLA code is reported instead of `81479`.
`88184`	Interpretation of molecular cytogenetic or molecular pathology test results (may be used for separate professional component reporting in some payor policies)	May be reported by the pathologist or molecular geneticist when separate interpretive services are billed; check payer rules for bundling with `0498U`.
`36415`	Collection of venous blood by venipuncture	Used when a peripheral blood specimen is collected for ctDNA analysis accompanying the `0498U` panel.
`88305`	Level III surgical pathology, gross and microscopic examination	Used when pathologist performs initial histopathology assessment of FFPE tissue prior to molecular testing; typically billed separately from the molecular test.
`G9999`	Placeholder for payer-specific molecular billing instructions	Some payors use local or HCPCS-level guidance for billing proprietary tests; inclusion here represents administrative steps adjacent to `0498U`.

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Summary & Overview

CPT 0498U: OptiSeq™ Colorectal Cancer NGS and Methylation Panel

Headline: New PLA CPT code 0498U designates the OptiSeq™ Colorectal Cancer NGS Panel, a proprietary next-generation sequencing (NGS) and methylation assay for colorectal cancer.

Key payers covered: Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0498UCPTProprietary Laboratory AnalysisNext-Generation SequencingColorectal CancerMethylation PanelLaboratory MedicineGenetic Testing

Billing Code Overview

Service type: Next-generation sequencing (NGS) tumor and circulating biomarker panel with methylation analysis

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`00`	Standard/Not otherwise specified modifier placeholder (per input list)	Use when no additional modifier applies; report `0498U` without special circumstance modifier when standard testing performed.
`22`	Increased procedural services	Use when additional work, such as substantially greater technical or interpretive effort, is documented (e.g., complex repeat testing, extensive microdissection of FFPE tissue).
`52`	Reduced services	Use when the test is partially reduced or an abbreviated panel is performed and documentation supports a reduced service.
`53`	Discontinued procedure	Use when testing was initiated but discontinued for documented reasons (e.g., inadequate specimen) prior to completion.

Taxonomy Code	Specialty	Notes
`207RG0100X`	Hematology & Oncology	Medical oncologists commonly order tumor genomic profiling for targeted therapy selection.
`207RH0000X`	Medical Oncology	Oncology subspecialists managing colorectal cancer care order and interpret NGS reports.
`2085P0207X`	Pathology	Surgical pathologists oversee tissue processing, microdissection, and specimen adequacy assessment.
`363L00000X`	Clinical Laboratory	Clinical molecular/pathology laboratories perform the NGS assay under CLIA certification.
`207K00000X`	Gastroenterology	Gastroenterologists may order testing at diagnosis or for recurrence evaluation.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C18.9`	Malignant neoplasm of colon, unspecified	Common indication for colorectal cancer molecular profiling to guide therapy and prognostic assessment.
`C20`	Malignant neoplasm of rectum	Rectal cancers benefit from NGS profiling for actionable mutations and potential targeted therapies.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Used when testing is performed for surveillance or recurrence risk assessment in a patient with prior colorectal cancer.
`C78.7`	Secondary malignant neoplasm of liver and intrahepatic bile duct	When metastatic disease is present, tumor profiling from metastasis or blood can inform systemic therapy.
`R97.2`	Elevated carcinoembryonic antigen [CEA]	Rising tumor marker prompting molecular testing for recurrence or residual disease evaluation.
`Z15.09`	Genetic susceptibility to other malignant neoplasm	When germline risk or family history prompts targeted methylation or mutation assessment as part of broader evaluation.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81479`	Unlisted molecular pathology procedure	Used when a specific proprietary PLA code is not available; for `0498U` the PLA code is reported instead of `81479`.
`88184`	Interpretation of molecular cytogenetic or molecular pathology test results (may be used for separate professional component reporting in some payor policies)	May be reported by the pathologist or molecular geneticist when separate interpretive services are billed; check payer rules for bundling with `0498U`.
`36415`	Collection of venous blood by venipuncture	Used when a peripheral blood specimen is collected for ctDNA analysis accompanying the `0498U` panel.
`88305`	Level III surgical pathology, gross and microscopic examination	Used when pathologist performs initial histopathology assessment of FFPE tissue prior to molecular testing; typically billed separately from the molecular test.
`G9999`	Placeholder for payer-specific molecular billing instructions	Some payors use local or HCPCS-level guidance for billing proprietary tests; inclusion here represents administrative steps adjacent to `0498U`.