Billing and Coding: Genetic Testing for Oncology

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.

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**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**

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  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.