Article - Billing and Coding: MolDX: Targeted and Comprehensive Genomic Profile Testing in Cancer (A55624)

CMS National Coverage PolicyN/AArticle TextNext Generation Sequencing (NGS)NGS allows identification of somatic and/or germline alterations in multiple genes simultaneously. This guideline focuses on Targeted and Comprehensive Genomic Profile testing for somatic variant detection using tumor-based panels for cancer that may be performed by NGS.Refer toMolDX: Defining panel services in MolDX (A59865)forfurther guidance on the distinction between single analyte and panel tests.Definitions:Targeted Tumor PanelsTargeted tumor panels are hereby defined as tests that identify somatic alterations known to occur in certain regions (i.e.,'hotspots') within specific genes of interest for cancer management (i.e., diagnosis, selection of molecularly targeted therapies, prognosis in a context where prognostic classification is essential for treatment selection). Generally, these panels are limited to specific variant types at defined sites, such as single nucleotide variants (SNVs), small insertions or deletions (INDELs), single site copy number variants, or gene fusions. These alterations typically represent response or lack of response to corresponding targeted cancer therapies. The hotspot test should include relevant targets required for companion diagnostic testing and/or known to be necessary for proper patient management.Comprehensive Genomic Profile (CGP) TestingCGP testing refers to NGS-based molecular assays that provide additional insight beyond individual gene hotspots; these assays seek to describe the genomic makeup of a tumor and can help identify underlying mechanisms of disease to guide clinical decision making. These tests include not only mutations in individual relevant genes, but also patterns of mutations across related genes in established cancer pathways and often include an assessment of overall mutational burden. These tests typically involve sequencing of entire exonic regions of genes of interest within a comprehensive gene panel or whole exome sequencing and may also include select intronic regions. CGP tests can detect multiple types of molecular alterations (i.e., SNVs, small and large INDELs, copy number variants (CNVs), structural variants (SVs), and splice-site variants) in a single assay. Patterns of mutations seen across multiple genes may be used to infer clinically relevant etiologies, such as DNA mismatch repair deficiency and microsatellite instability (MSI), total mutational load/burden (TMB) and chromosome abnormalities such as loss of heterozygosity (LOH). CGP testing may also include RNA sequencing to detect structural variations, such as translocations or large deletions, and to detect functional splicing mutations. CGP testing is not defined as a targeted panel by MolDX. CGP tests are expected to yield information of clinical relevance beyond a targeted panel, for example, to identify relevant clinical trials for patient management or identify possible therapeutic interventions for off-label use. It is expected that a CGP will identify all clinically relevant information attainable for the type of service performed.CPT coding InstructionsTargeted Tumor PanelsTo bill for DNA-based panels that measure specific SNVs, INDELs, CNVs or rearrangements, review CPT codes 81445 and 81450. If a DNA-based targeted panel meeting the coverage requirements is used, and MSI is also performed, 81457 can be billed. If a DNA-based targeted test meeting coverage requirements is performed that includes MSI and CNVs, 81458 can be billed.81449 or 81451 for RNA-based targeted testing may also be billed for the same specimen that received a DNA-based NGS test if compliant with the language of A57503, is non-duplicative, and performed serially to DNA testing as a separate service (with a separate order and report). If only RNA-based testing is reasonable and necessary, 81449 or 81451 may be billed alone if policy requirements are met. If two targeted panels (one for DNA and the other for RNA) are always performed together and meet policy criteria, 81479 should be used for such a service to reduce claims processing errors as this would constitute one service.The unit of service (UOS) for an NGS gene panel is one (UOS=1). Providers must also provide the approved DEX Z-Codeidentifier for the test.Effective July 1, 2017, laboratories with 2 to 4 genes on their targeted NGS panel should use CPT 81479 and one (1) UOS along with their test identifier (DEX Z-Code) to represent this service on their claims.CGPCPT code 81459, based on the inclusion of the comprehensive test components addressed in the definition above, is considered a CGP test by this contractor and may be billed when all stated components of the service have satisfied technical assessment requirements. Because this code includes both DNA-only and DNA/RNA combined services in its description, it is assumed that services that include DNA/RNA combined testing add no additional relevant genomic information beyond that provided by a DNA-only test. For CGP tests that include the use of RNA to interrogate relevant genomic information beyond that captured with DNA-based testing, billing with CPT 81479 is appropriate. Additionally, if a service meets the definition of a CGP but NOT 81459, CPT code 81479 is appropriate.Therefore, to report a CGP service, test providers should use CPT codes 81459 or 81479, in addition to the approved DEX Z-Codefor the test. Coverage of CGPs is limited to one test per surgical specimen and precludes the use of any further molecular testing on that specimen.For NGS-based tests that do not fit under the above definitions of targeted or Comprehensive panels, billing with the Not Otherwise Classified (NOC) code 81479 along with the approved DEX Z-Codeidentifier is appropriate.Tier 1 and/or Tier 2 individual biomarker CPT codes should not be used for a single gene or any combination of genes when testing is performed as part of a NGS or other multiplexing technology panel.Refer toBilling and Coding: MolDX: Next-Generation Sequencing for Solid Tumors A57901for CPT/HCPCS codes and ICD-10 codes relevant for solid tumors.Refer toBilling and Coding: MolDX: Next-Generation Sequencing Lab-Developed Tests for Myeloid Malignancies and Suspected Myeloid Malignancies A57891for CPT/HCPCS codes and ICD-10 codes relevant for myeloid malignancies.