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

National Correct Coding Initiative (NCCI) Policy Manual for Medicare Services:

• 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 Proposed Local Coverage Determination (LCD) DL39365 Genetic Testing for Oncology. Please refer to the LCD for reasonable and necessary requirements.

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

Molecular code descriptions of the AMA CPT Manual in general 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 common variants or duplication/deletion variants.
• As stated in the NCCI Coding Policy Manual, these codes in general should not be billed together except in uncommon scenarios where it is reasonable and necessary, such as billing a code for “full gene sequence” with another code for “duplication/deletion variants” when both tests are required to evaluate a patient’s documented disease.

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 Manual. 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 Manual and the NCCI Policy Manual for Medicare Services 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 1 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 88373 since only 1 single probe procedure was used, regardless of how many slides are made with the single source specimen.
  • If 2 different single probe procedures are used to evaluate several slides from 1 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 1 single probe procedure is used on 2 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 88373 since only 1 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 81455 covers 51 or greater genes.
• This means any test matching the CPT code description for 81455, regardless of whether the test analyzed 52 genes or 200 genes, would be billed under the 81455 code with only 1 UOS.
• 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.

GSP CPT codes can also list specific genes that are required to be on a testing panel (e.g., see CPT code 81437 – “Hereditary neuroendocrine tumor disorders”); any gene panel that does not include all required genes cannot be billed with that CPT code.

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:

• Gene expression profiling (GEP) can be performed using a Next Generation Sequencing (NGS) methodology, as defined in the CPT code 0153U – Oncology (breast), mRNA, gene expression profiling by next-generation sequencing of 101 genes
• In other cases, GEP can be performed using quantitative PCR (real-time PCR) methodology, as defined in the CPT code 0005U – Oncology (prostate) gene expression profile by real-time RT-PCR of 3 genes (ERG, PCA3, and SPDEF), urine, algorithm reported as risk score.

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).

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 manual describe specific parameters that limit a code’s scope of coverage. Definitions are frequently provided at the beginning of sections and subsections within the AMA CPT Manual. 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: Testing that focuses on (targets) a specific part(s) of a gene.

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.

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.

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 coverage information regarding CPT codes 81327 and 0229U, please refer to NCD 210.3 Colorectal Cancer Screening Tests.

Utilization Parameters

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

The following tests may only be reported once per beneficiary lifecycle:

• 81202
• 81215
• 81217
• 81308
• 81318
• 81322
• 81353
• 81432
• 81433
• 81435
• 81436
• 81437
• 81438
• 0101U
• 0102U
• 0103U
• 0129U
• 0130U
• 0135U
• 0162U

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.