Billing and Coding: Genetic Testing for Oncology

Internet-Only Manuals (IOMs):

• CMS IOM Publication 100-04, Medicare Claims Processing Manual,
  • Chapter 16, Section 10 Background, Section 40.8 Date of Service (DOS) for Clinical Laboratory and Pathology Specimens and Section 120.1 Negotiated Rulemaking Implementation
  • Chapter 18 Preventive and Screening Services
• CMS IOM Publication 100-08, Medicare Program Integrity Manual,
  • Chapter 3 Verifying Potential Errors and Taking Corrective Actions

Social Security Act (Title XVIII) Standard References:

• Title XVIII of the Social Security Act, Section 1833(e) states that no payment shall be made to any provider of services or other person under this part unless there has been furnished such information as may be necessary in order to determine the amounts due such provider or other person under this part for the period with respect to which the amounts are being paid or for any prior period.

Code of Federal Regulations (CFR) References:

• CFR, Title 42, Subchapter B, Part 410 Supplementary Medical Insurance (SMI) Benefits, Section 410.32 Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions
• CFR, Title 42, Section 414.502 Definitions
• CFR, Title 42, Subpart G, Section 414.507 Payment for clinical diagnostic laboratory tests and Section 414.510 Laboratory date of service for clinical laboratory and pathology specimens
• CFR, Title 42, Part 493 Laboratory Requirements
• CFR, Title 42, Section 493.1253 Standard: Establishment and verification of performance specifications
• CFR, Title 42, Section 1395y(b)(1)(F) Limitation on beneficiary liability

Medicare National Correct Coding Initiative (NCCI) Policy Manual:

• Chapter 10, Section F Molecular Pathology
• Chapter 10, Section M Medically Unlikely Edits (MUEs)

This Billing and Coding Article provides billing and coding guidance for Local Coverage Determination (LCD) L39365 Genetic Testing for Oncology. Please refer to the LCD for reasonable and necessary requirements.

All instructions provided within the American Medical Association (AMA) Current Procedural Terminology (CPT) Codebook with rules and guidelines from the AMA’s CPT Editorial Panel and the Medicare NCCI Policy Manual should be followed when utilizing CPT codes for billing. Proper coding involves interpreting code descriptions provided by these sources as well as any associated parentheticals. The instructions below do not represent the full breadth or depth of instructions found in the CPT Codebook and the Medicare NCCI Policy Manual. Providers that bill Medicare are expected to follow all instructions found in these sources.

Molecular code descriptions in the CPT Codebook generally have some or all of the following components:

1. Medical condition under investigation
2. Genetic content to be tested
3. Technology/methodology used for testing
4. Specimen type evaluated

Providers must ensure that their use of molecular CPT codes represent the highest level of specificity in what testing was performed. The following reviews each of these components with general tips for each:

1. Medical Condition

When a code designates coverage of a specific medical condition (e.g., CPT code 81432 - “Hereditary breast cancer- related disorders”), all genes billed under this code must fall under the description of the medical condition. Even if all the genes described by a CPT code are tested in a claim, the CPT code can only be used if the described medical condition matches the documented disease.

2. Genetic Content

Commonly, molecular CPT codes have a gene(s) listed within their coding description. Special attention must be paid to what elements of a gene are analyzed since not all codes describe the analysis of an entire gene. A gene could be tested for a single well-known variant (e.g., CPT code 81210 - V600 variants in the BRAF gene) or the gene could be fully sequenced (e.g., CPT code 81406 – full sequence of the BRAF gene). In fact, several codes in the Tier 1 molecular section cover the same gene but differ in what element of that gene they cover.

• For instance, the CPT codes 81201, 81202, and 81203 all describe tests for the same gene, APC, but cover different elements of the gene such as full gene sequence, known familial variants or duplication/deletion variants.
• As stated in the Medicare NCCI Policy Manual Chapter 10, these codes in general should not be billed together. An exception could be in uncommon scenarios such as billing a code for “full gene sequence” with another code for “duplication/deletion variants” when the disease variants cannot be identified by performing full gene sequencing. “Procedures reported together must be both medically reasonable and necessary (e.g., sequencing of procedures) and ordered by the physician who is treating the beneficiary and using the results in the management of the beneficiary's specific medical problem.”

Less commonly, molecular CPT codes are defined by only a test methodology, as is seen in codes for Fluorescence In Situ Hybridization (FISH) found in the Surgical Pathology section of the CPT Codebook. In brief, FISH is a technique where a probe (a short, single-stranded nucleic acid sequence) targets a specific genetic sequence and is labeled/tagged with a fluorescent dye. If the target is found, the fluorescent dye becomes attached to that target and can be seen under microscopy or other related imaging. In oncology, FISH probes are used to evaluate many different genes for many different cancers; however, many FISH CPT codes do not specify which genes or which cancers are being evaluated. As a result, special attention must be paid to what unit of service (UOS) is found in the code description.

A UOS for FISH testing could be defined in numerous ways, including number of slides evaluated, number of single source specimens evaluated, number of FISH probes used, number of FISH procedures performed, or number of cells counted. For Medicare, both the CPT Codebook and the Medicare NCCI Policy Manual specify which of these UOS applies, and billing for more UOS than were actually performed is not permitted.

The NCCI manual states that regardless of how many blocks or slides are created from a surgical, cytologic, or hematologic specimen, testing multiple blocks or slides from the same specimen source (e.g., tube of blood) still is considered as 1 UOS per source specimen.

For example:

• The UOS described for CPT code 88373 is both “per specimen” and “each additional single probe stain procedure.” Depending on the testing scenario, the code may or may not be used, and should only be used in relation to additional probes NOT additional specimens.
  • If one single probe procedure is used for a specimen from one source (e.g., right iliac crest bone marrow aspiration), only 1 UOS may be claimed, even if multiple slides from the specimen are tested with the same probe:
  • 1 UOS with the parent CPT code 88367,
  • 0 UOS should be reported with CPT code 88373 since only one single probe procedure was used, regardless of how many slides are made with the single source specimen.
• If two different single probe procedures are used to evaluate several slides from one source specimen, only 2 UOS may be claimed:
  • 1 UOS with the parent CPT code 88367, AND
  • 1 UOS with the additional CPT code  88373
• If one single probe procedure is used on two source specimens (e.g., one bone marrow aspiration specimen from the right iliac crest and another specimen from the left iliac crest), only 2 UOS may be claimed:
  • 2 UOS with the parent CPT code 88367,
  • 0 UOS should be reported with CPT code 88373 since only one single probe procedure was used.
• The same logic for single probe stain procedures is also true of using multiplex probe stain procedures (CPT code 88374); the UOS is based on the overall multiplex probe stain procedure NOT the number of probes within the multiplex stain.

CPT codes that describe a genomic sequencing panel (GSP) often include instructions that define the number of genes covered, for instance using a range (5-50 genes) or using a minimum number required (e.g., “at least” 10 genes).

For instance:

• CPT code 81436 covers at least five genes and must include the genes MLH1, MSH2, EPCAM, SMAD4, and STK11.
• This means any test matching the CPT code description for 81436, regardless of whether the test analyzed five genes or 20 genes, would be billed under the CPT code 81436 code with only 1 UOS.
• Additionally, this means that any test without all five mandatory genes (MLH1, MSH2, EPCAM, SMAD4, and STK11) would NOT be billed with this code.
• When a CPT code for a panel is used in this context, no other CPT codes may be used to describe the panel, regardless of presence or absence of modifiers.

3. Technology/Methodology

When a CPT code description specifies a particular technology and/or testing methodology, only that technology and/or methodology may be used when billing that code. Therefore, special attention must be paid to the full code description, especially if the type of content tested has technology that typically varies from CPT code to CPT code. For example, CPT codes describing a gene expression profiling (GEP) test often include the specific methodology used for that test, such as RT-PCR (e.g., 81518), microarray (e.g., 81521), and next-generation sequencing (e.g., 81523).

Conversely, if a technology and/or methodology is NOT specified in a code description, there is no need to match the technology and/or methodology to that code (e.g., a full sequence analysis of three different genes can be performed by Sanger Sequencing or NGS). For example, CPT code 81279 describes targeted sequence analysis for the gene JAK2 without specifying a sequencing technology. JAK2 is often part of a sequence of reflexive tests evaluating for a myeloproliferative neoplasm, and commonly each step is performed using real time/quantitative (RT/q) PCR. However, each step of that testing sequence could also be performed with Sanger sequencing technology. Additionally, JAK2 could be part of a small NGS panel test with other genes, which, if less than five genes, could be billed as CPT code 81279 and three additional CPT codes representing three other genes. Finally, as technology advances, whole exome/genome sequencing is being utilized more and more as a backbone to customized testing, wherein all unanalyzed data is masked (only certain genetic content is made visible while the rest of the data is hidden from the interpreter) and only a smaller set of genes is analyzed and billed. The benefit to this newer method is the collected data can be reanalyzed as additional customized panels by unmasking additional genetic content without having to rerun the whole exome/genome sequencing. Again, if the custom panel is small, CPT code 81279 would be billed in tandem with up to three other gene codes.

Per the Medicare NCCI Policy Manual Chapter 10, “A Tier 1 or Tier 2 molecular pathology procedure CPT code should not, in general, be reported with a genomic sequencing procedure, molecular multianalyte assay, multianalyte assay with algorithmic analysis, or proprietary laboratory analysis CPT code where the CPT code descriptor includes testing for the analyte described by the Tier 1 or Tier 2 molecular pathology code. Procedures reported together must be both medically reasonable and necessary (e.g., sequencing of procedures) and ordered by the physician who is treating the beneficiary and using the results in the management of the beneficiary's specific medical problem.”

4. Specimen Type

Some CPT codes (particularly PLA codes) define what type of specimens or specimen sources are covered by the code description. For instance, some multianalyte assays with algorithmic analyses evaluate gene expression in tumor tissue. Sometimes these tests are restricted to fresh tissue whereas other tests have been optimized to use formalin-fixed, paraffin-embedded tissue. These definitions are often clearly stated within the CPT code description and must be followed when present.

Definitions

Providers should be familiar with all terminology found within the CPT code descriptions before billing Medicare for these codes. Many of the molecular terms utilized in the CPT Codebook describe specific parameters that limit a code’s scope of coverage. Definitions are frequently provided at the beginning of sections and subsections within the CPT Codebook. The following are selected definitions of terminology and phrases commonly seen in the code descriptions:

• “always including”/“must include”: Targets that are required in testing described by a CPT code.
• “at least”/“or greater”: Minimum number of genes required to bill for a specific CPT code.

• • For instance, if a CPT code description for a panel requires “at least” 10 genes, this means the panel size must, at minimum, analyze 10 genes. However, if the panel analyzes 11, 20, 50, or 100 genes and this code is used, no other codes may be used to describe the panel, regardless of presence or absence of modifiers.

• Common variants/Common deletions/etc.: Genetic variants most predominantly associated with a disease, as defined by professional society guidelines. Billing CPT codes with “common” variants in the code description should not include testing for uncommon and/or rare variants. If a variant is felt to be “common,” this designation must be supported by a professional society’s guidelines.
• Deletion/duplication analysis: Testing that evaluates for loss (deletion) or gain (duplication) of stretches of genetic sequence (dosage of a particular genomic region).
• “e.g.,”: Examples of … Depending on the context, listed examples following an “e.g.,” may or may not be required in the testing described by a code.
• Full gene sequence/full sequence analysis: Testing that evaluates, at a minimum, all exons of a gene. Depending on the testing methodology used, a full sequence analysis may also include additional non-coding sequence (e.g., promotor region, introns) and/or may NOT include data on certain types of variants, such as duplication/deletion variants.
• Qualitative: Results of a test provided as descriptive terms (e.g., positive, negative, inconclusive).
• Quantitative: Results of a test provided as numeric measurements/values (e.g., International Units per milliliter [IU/mL]).
• Targeted genomic sequence analysis/targeted sequence analysis: Typically defined as testing that focuses on (targets) a specific part(s) of a gene. This term is also used to describe selective review of larger regions of the genome when the term is used in the context of more comprehensive sequencing, such as whole genome/exome sequencing.

Coding Guidance

Notice: It is not appropriate to bill Medicare for services that are not covered (as described by the entire LCD) as if they are covered. When billing for non-covered services, use the appropriate modifier.

Per the Medicare NCCI Policy Manual Chapter 10, “CPT codes 81445, 81450, and 81455 describe targeted genomic sequence, DNA analysis or combined DNA and RNA analysis. CPT code 81445 applies to solid organ neoplasm type (5-50 genes) and CPT code 81450 applies to hematolymphoid neoplasm type (5-50 genes), while CPT code 81455 applies to the number of genes analyzed for either a solid or hematolymphoid neoplasm (51 or greater genes). Providers/suppliers may not report CPT code 81455 with either CPT code 81445 or 81450. CPT codes 81449, 81451, and 81456 describe targeted genomic sequence RNA analysis using a separate method.”

“All genomic sequencing procedures and molecular multianalyte assays (e.g., CPT codes 81410-81471), many multianalyte assays with algorithmic analyses (e.g., CPT codes 81490-81599, 0004M-XXXXM), and many Proprietary Laboratory Analyses (PLA) (e.g., CPT codes 0001U-XXXXU) are DNA or RNA analytic methods that simultaneously assay multiple genes or genetic regions. A provider/supplier shall not separately report testing for the same gene or genetic region by a different methodology (e.g., CPT codes 81105-81408, 81479, 88364-88377). CMS payment policy does not allow separate payment for multiple methods to test for the same analyte.”

“If one laboratory procedure evaluates multiple genes using a next generation sequencing procedure, the laboratory shall report only one unit of service of one genomic sequencing procedure, molecular multianalyte assay, multianalyte assay with algorithmic analysis, or proprietary laboratory analysis CPT code. If no CPT code accurately describes the procedure performed, the laboratory may report CPT code 81479 (Unlisted molecular pathology procedure) with one unit of service or may report multiple individual CPT codes describing the component test results when medically reasonable and necessary. Procedures reported together must be both medically reasonable and necessary (e.g., sequencing of procedures) and ordered by the physician who is treating the beneficiary and using the results in the management of the beneficiary's specific medical problem.”

For tests that are genomic sequencing procedures that simultaneously assay multiple genes or genetic regions, coverage would be dependent on the genetic content examined and whether the content is covered for the patient’s specific medical condition by the LCD.

• A targeted genomic sequence analysis panel that tests 5 to 50 genes and contains genes that meets LCD coverage criteria for the management of the patient’s specific medical condition to improve the patient’s outcome may be billed with CPT codes 81445, 81449, 81450, or 81451.
• A targeted genomic sequence analysis panel that tests for 51 or greater genes and contains genes that meets LCD coverage criteria for the management of the patient’s specific medical condition to improve the patient’s outcome may be billed with the CPT codes 81455 or 81456.
• A targeted genomic sequence analysis panel that tests five or greater genes and contains NO genetic content covered by the LCD criteria is billed with CPT codes 81445, 81449, 81450, 81451, 81455, or 81456 and the appropriate modifier to indicate a non-covered service.

It would not be expected that providers would perform, for an oncologic condition, a genomic sequencing procedure (e.g., next generation sequencing) that simultaneously assays multiple genes or genetic regions which would not be accurately described by CPT codes 81445, 81449, 81450, 81451, 81455 or 81456. Frequent utilization of CPT code 81479 and/or multiple individual CPT codes describing the component test results will be subject to review.

Note: For coverage information regarding CPT codes 0022U, 0037U, 0111U, 0172U, 0239U, and 0242U, please refer to NCD 90.2 Next Generation Sequencing (NGS).

Note: For all DNA-only NGS testing for non-hematologic malignancies, the NCD 90.2 section B or section D criteria must be met.

The NCD 90.2 is only applicable to DNA sequencing diagnostic laboratory tests using NGS for non-hematologic, somatic (acquired) and germline (inherited) cancers.

• For non-hematologic DNA sequencing NGS tests that meet CMS FDA approval or clearance in NCD 90.2 section B.1.b. or section B.2.b., follow NCD requirements in section B.1.a. or section B.2.a.
• For non-hematologic DNA sequencing NGS tests that do not meet CMS NCD 90.2 section B requirements that are performed in CLIA-certified laboratories, refer to NCD 90.2 section D AND the LCD for coverage criteria.
• For NGS tests with combined DNA and RNA analysis of somatic and germline cancers, RNA analysis of somatic and germline cancers, and NGS tests for hematologic cancers, refer to the LCD for coverage criteria.

Note: For coverage information regarding CPT codes 88230 through 88291, please refer to NCD 190.3 Cytogenetics Studies.

Note: For coverage information regarding CPT code 81327 and 81528, please refer to NCD 210.3 Colorectal Cancer Screening Tests.

Note: Unlisted CPT codes 81479, 81599, and 88299 will be reviewed on a claim-by-claim basis to determine if coverage criteria in an NCD and/or an LCD are met. Include the gene(s) or specific laboratory test name on the claim and submit documentation with the claim to support the service was performed and mets LCD coverage criteria.

For coding guidance on Tier 1 and Tier 2 codes, CPT code 81479 (Unlisted Molecular Pathology), testing for multiple genes, -59 Modifier, Next Generation Sequencing (NGS), Genomic Sequencing Profiles (GSP), Multianalyte Assays with Algorithmic Analyses (MAAAs) and Proprietary Laboratory Analyses (PLAs), please refer to the billing and coding article A58917 Molecular Pathology and Genetic Testing.

Table 1. Tier 2 codes’ genes meeting LCD coverage criteria

Utilization Parameters

Genetic testing for hereditary cancer syndromes is considered germline testing, and therefore only permitted once per beneficiary’s lifecycle.

The following tests are germline tests:

• 81202
• 81215
• 81217
• 81293
• 81296
• 81299
• 81308
• 81318
• 81322
• 81353
• 81432
• 81433
• 81435
• 81436
• 81437
• 81438
• 0101U
• 0102U
• 0103U
• 0129U
• 0130U
• 0131U
• 0132U
• 0133U
• 0134U
• 0135U
• 0162U
• 0238U

Documentation Requirements

1. All documentation must be maintained in the patient's medical record and made available to the contractor upon request.
2. Every page of the record must be legible and include appropriate patient identification information (e.g., complete name, dates of service[s]). The documentation must include the legible signature of the physician or non-physician practitioner responsible for and providing the care to the patient.
3. The submitted medical record must support the use of the selected ICD-10-CM code(s). The submitted CPT/HCPCS code(s) must describe the service performed.
4. The medical record must demonstrate that the treating clinician who is responsible for the management of the patient’s cancer or substantiated suspicion of cancer is the same person as the ordering clinician.
5. The medical record must include documentation to support an established diagnosis of cancer or a substantiated suspicion of cancer.
6. The medical record must include documentation of how the test results will directly impact the management of the patient’s specific medical problem.
7. The medical record must clearly document the communication and discussion of pre-test and post-test counseling and the risk associated with genetic testing.
8. The medical record from the ordering clinician must clearly indicate all tests that are to be performed.