Highmark Commercial Medical Policy - Pennsylvania


 
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Medical Policy: L-184-005
Topic: Hereditary Cancer Syndrome Multigene Panels
Section: Laboratory
Effective Date: November 13, 2017
Issue Date: November 13, 2017
Last Reviewed: June 2017

When a mutation in a single gene causes a significantly increased risk for certain cancers, it is called a hereditary cancer syndrome.  Hereditary cancer syndromes are usually characterized by a pattern of specific cancer types occurring together in the same family, younger cancer diagnosis ages than usual, and/or other coexisting non-cancer conditions. There are at least 50 hereditary cancer syndromes.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Hereditary Cancer Syndrome Multigene Panels may be considered medical necessary when the following clinical criteria are met.

This policy applies to all hereditary cancer syndrome panels, which are defined as assays that simultaneously test for more than one hereditary cancer syndrome. This policy does not apply when testing more than one gene related to the same hereditary cancer syndrome (e.g., Lynch syndrome).

Medical necessity coverage generally relies on criteria established for testing individual hereditary cancer syndromes. See Tables 1 and 2 for examples of genes known to be included in currently available hereditary cancer syndrome multi-gene panels with coverage guidance. This is not intended to be a complete list of available genes as these panels are evolving rapidly.

However, this policy takes into account the efficiency gains from simultaneously testing multiple candidate genes. Therefore, coverage requirements rely to some degree on how the panel will be billed. Panels may be billed in a variety of ways:

  • Gene sequencing portion:
    • A separate CPT code for sequencing each gene studied or a subset (e.g., 81201, 81294, 81297, etc.)
    • A single CPT code developed specifically for a particular type of panel (e.g., 81432, 81435, 81437)
    • A single unlisted CPT code (e.g., 81479)
  • Deletion/duplication analysis portion:
    • A separate CPT code for deletion/duplication analysis of each gene studied or a subset (e.g., 81203, 81292, 81294, 81404, 81479, etc.)
    • A single CPT code developed specifically for a particular type of panel (e.g., 81433, 81436, 81438)
    • Microarray analysis (e.g., 81228 or 81229
    • Part of a single unlisted CPT code for the sequencing and deletion/duplication portions of the panel (e.g., 81479)

Hereditary cancer syndrome multi-gene panels may be considered medically necessary when the following criteria are met:

  • Panel will be billed with separate procedure codes for each gene analyzed (however, please note that the billed amount should not exceed the list price of the test).
    • The medical necessity of each billed procedure will be assessed independently. See Tables 1 and 2 below for gene-specific policy guidance.
      • When a patient meets medical necessity criteria for any hereditary cancer syndrome gene(s) included in a multi-gene panel, genetic testing for the clinically indicated gene(s) will be covered. This includes the sequencing and deletion/duplication* components.
      • Any genes that are included in a multi-gene panel but do NOT meet medical necessity criteria will NOT be a covered service. It will be at the laboratory, provider, and patient’s discretion to determine if a multi-gene panel remains the preferred testing option.
    • Sequencing and/or deletion/duplication analysis* of any hereditary cancer syndrome gene(s) should only be performed once per lifetime and will therefore only be covered once (1) per lifetime. If gene testing was previously performed, and is now being included in a panel, such testing will not be separately reimbursable regardless of whether clinical coverage criteria are met; or
  • Panel will be billed with a single procedure code to represent all genes being sequenced, with or without another single procedure code representing the deletion/duplication analysis* portion. Code(s) may be specific to that panel or an unlisted code, such as 81479.
    • No previous hereditary cancer syndrome testing has been performed.
      • Medical necessity must be established for at least two (2) conditions included in the panel (e.g., hereditary breast and ovarian cancer and Li Fraumeni syndrome). Note that this is two conditions and not two genes (i.e., meeting criteria for only Lynch syndrome, which is caused by mutations in at least 5 genes, would not fulfill criteria alone).
    • Testing for one (1) condition was performed and billed separately. A multigene panel is now being considered as a reflex and will be billed at a rate comparable to single syndrome pricing (e.g., myRisk update).
      • Medical necessity must be established for at least one (1) condition included in the panel in addition to the already tested condition (e.g., hereditary breast and ovarian cancer was already performed, but Lynch syndrome criteria are also met).

*When deletion/duplication testing is not part of a single panel CPT code being billed, deletion/duplication testing should be billed in only one of the following ways:

  • A separate CPT code for deletion/duplication analysis of each individual gene (may include non-specific molecular pathology tier 2 codes or unlisted code 81479); or
  • A single CPT code specific to the performed deletion/duplication analysis panel; or
  • A single microarray procedure.

Procedure codes representing multiple methods for deletion/duplication testing will not be reimbursable for the same panel (e.g., test-specific deletion/duplication procedure codes and microarray will not both be reimbursable for the same panel).

When the above criteria are not met, hereditary cancer syndrome multi-gene panels are considered not medically necessary.

For all other indications not listed above in this policy, hereditary cancer syndrome multi-gene panels are considered not medically necessary.

Table 1  Covered Genes Included in Hereditary Cancer Syndrome Multi-Gene Panels 

Condition

Test Name

CPT

Birt-Hogg-Dube syndrome

FLCN Sequencing

81479

 

FLCN
Deletion/Duplication
Analysis

81479

Cowden syndrome, PTEN hamartoma tumor syndrome

PTEN
Deletion/Duplication
Analysis  

81323

 

PTEN Sequencing

81321

Cutaneous malignant melanoma

CDK 4 Deletion/Duplication Analysis

81479

 

CDK4 Exon 2 Sequencing

81479

 

CDKN2A Deletion/Duplication Analysis

81479

 

CDKN2A Sequencing

81404

Familial adenomatous polyposis

APC Deletion/Duplication Analysis

81203

 

APC Sequencing

81201

Familial Wilms tumor

WT1 Sequencing

81405

Hereditary breast and ovarian cancer

BRCA1/2 Sequencing

81211 

 

BRCA1/2 Deletion/Duplication Analysis

81213

 

BRCA1 Sequencing

81214

 

BRCA2 Sequencing

81216

Hereditary diffuse gastric cancer

CDH1 Sequencing

81406

 

CTNNA1 Deletion/Duplication Analysis

81479

 

CTNNA1 Sequencing

81479

Hereditary leiomyomatosis with renal cell cancer

FH Sequencing

81405

Hereditary mixed polyposis syndrome,
Juvenile polyposis syndrome

BMPR1A Deletion/Duplication Analysis

81479

 

BMPR1A Sequencing

81479

Hereditary papillary renal cell carcinoma

MET Sequencing

81479

 

MET Deletion/Duplication Analysis

81479

Hereditary paragangliomapheochromocytoma syndromes

SDHA Sequencing

81406

 

SDHB Deletion/Duplication Analysis

81479

 

SDHB Sequencing

81405

 

SDHC Deletion/Duplication Analysis

81404

 

SDHC Sequencing

81405

 

SDHD Deletion/Duplication Analysis

81479

 

SDHD Sequencing

81404

 

MAX Sequencing

81479

 

MAX Deletion/Duplication Analysis

81479

 

SDHAF2 Sequencing

81479

 

SDHAF2 Deletion/Duplication Analysis

81479

 

TMEM127 Sequencing

81479

 

TMEM127 Deletion/Duplication Analysis

81479

Juvenile polyposis syndrome

SMAD4 Deletion/Duplication Analysis

81405

 

SMAD4 Sequencing

81406

Li-Fraumeni syndrome

TP53 Deletion/Duplication Analysis

81479

 

TP53 Sequencing

81405

 

TP53 Targeted Sequencing

81404

Lynch syndrome

EPCAM Deletion/Duplication Analysis

81403

 

MLH1 Deletion/Duplication Analysis

81294

 

MLH1 Sequencing

81292

 

MSH2 Deletion/Duplication Analysis

81297

 

MSH2 Sequencing

81295

 

MSH6 Deletion/Duplication Analysis

81300

 

MSH6 Sequencing

81298

 

PMS2 Deletion/Duplication Analysis

81319

 

PMS2 Sequencing

81317

Multiple endocrine neoplasia type 1

MEN1 Deletion/Duplication Analysis

81404

 

MEN1 Sequencing

81405

Multiple endocrine neoplasia, type 2A

RET Sequencing

81406

 

RET Targeted Sequencing

81405

MUTYH-associated polyposis

MUTYH Deletion/Duplication Analysis

81479

 

MUTYH Sequencing

81406

Neurofibromatosis type

NF1 Deletion/Duplication Analysis

81479

 

NF1 Sequencing

81408

Peutz-Jeghers syndrome

STK11 Deletion/Duplication Analysis

81404

 

STK11 Sequencing

81479

von Hippel-Lindau syndrome

VHL Deletion/Duplication Analysis

81403

 

VHL Sequencing

81404

Procedure Codes
81479, 81323, 81321, 81403, 81404, 81405, 81406, 81408, 81203, 81201, 81211, 81213, 81214, 81216, 81292, 81294, 81295, 81297, 81298, 81300, 81317, 81319


Table 2   Not Covered Genes Included in Hereditary Cancer Syndrome Multi-Gene Panels

The following Gene testing is not covered strictly for hereditary cancer indication. In general, this category applies to genes that have only a low to moderate impact on cancer risk (compared to high penetrance cancer syndrome-causing genes) and no clear management guidelines associated with identifying a mutation.

Condition

Test Name

CPT

Tumor Predisposition Syndrome

BAP1 Deletion/Duplication Analysis

81479

 

BAP 1 Sequencing

81479

Unknown Phenotype

CHEK1 Deletion/Duplication Analysis

81479

 

CHEK1 Sequencing

81479

 

RAD51B Deletion/Duplication Analysis

81479

 

RAD15B Sequencing

81479

Von Hippel-Lindau Syndrome

VHL Deletion/Duplication Analysis

81403

 

VHL Sequencing

81404

Familial breast and/or ovarian cancer

AKT1 Deletion/Duplication Analysis

81479

 

AKT1 Sequencing

81479

 

ATM Deletion/Duplication Analysis

81479

 

ATM Sequencing

81408

 

BARD1 Deletion/Duplication Analysis

81479

 

BARD1 Sequencing

81479

 

BRIP1 Deletion/Duplication Analysis

81479

 

BRIP1 Sequencing

81479

 

CHEK2 Deletion/Duplication Analysis

81479

 

CHEK2 Sequencing

81479

 

FAM175A Deletion/Duplication Analysis

81479

 

FAM175A Sequencing

81479

 

GEN1 Deletion/Duplication Analysis

81479

 

GEN1 Sequencing

81479

 

MRE11A Deletion/Duplication Analysis

81479

 

MRE11A Sequencing

81479

 

NBN Deletion/Duplication Analysis

81479

 

NBN Sequencing

81479

 

RAD50 Deletion/Duplication Analysis

81479

 

RAD50 Sequencing

81479

 

RAD51 Deletion/Duplication Analysis

81479

 

RAD51 Sequencing

81479

 

RAD51C Deletion/Duplication Analysis

81479

 

RAD51C Sequencing

81479

 

RAD51D Deletion/Duplication Analysis

81479

 

RAD51D Sequencing

81479

 

SMARCA4 Deletion/Duplication Analysis

81479

 

SMARCA4 Sequencing

81479

 

XRCC2 Deletion/Duplication Analysis

81479

 

XRCC2 Sequencing

81479

 

XRCC3 Deletion/Duplication Analysis

81479

 

XRCC3 Sequencing

81479

Familial colorectal cancer

AXIN2 Deletion/Duplication Analysis

81479

 

AXIN2 Sequencing

81479

 

GALNT12 Deletion/Duplication Analysis

81479

 

GALNT12 Sequencing

81479

 

MLH3 Deletion/Duplication Analysis

81479

 

MLH3 Sequencing

81479

 

POLE Sequencing

81479

 

POLD1 Sequencing

81479

Familial cutaneous telangiectasia and cancer syndrome

ATR
Deletion/Duplication
Analysis

81479

 

ATR Sequencing

81479

Familial pancreatic cancer

PRSS1
Deletion/Duplication
Analysis

81479

 

PRSS1 Sequencing

81404

Familial prostate cancer

HOXB13
Deletion/Duplication
Analysis

81479

 

HOXB13 Sequencing

81479

Familial renal cell
carcinoma

MITF Sequencing

81479

 

MITF
Deletion/Duplication
Analysis

81479

Hereditary breast and pancreatic cancer

PALB2 Sequencing

81406

Hereditary mixed polyposis syndrome

GREM1
Deletion/Duplication
Analysis

81479

 

GREM1 Sequencing

81479


Refer to the following policies for additional information:

  • L-15 Lynch Syndrome Genetic Testing
  • L-106 Genetic Testing For Cancer Susceptibility and Hereditary Cancer Syndromes
  • L-123 Liquid Biopsy Testing-Solid Tumors
  • L-124 Tumor Marker Testing-Solid Testing
  • L-129 Li-Fraumeni Syndrome Testing
  • L-145 PTEN Hamartoma Tumor Syndromes Testing
  • L-149 Lynch Syndrome Tumor Screening – First Tier
  • L-150 Lynch Syndrome Tumor Screening – Second Tier
  • L-168 VonHipple-Lindau Disease Testing
  • L-172 Familial Adenomatous Polyposis Testing
  • L-177 MUTYH Associated Polyposis Testing
  • L-178 Peutz-Jeghers Syndrome Testing

Professional Statements and Societal Positions

Guidelines and Evidence

  • The National Comprehensive Cancer Network (NCCN) makes the following general recommendations for using multi-gene panels in evaluating risk for breast and ovarian cancer and now includes this option in some management algorithms:
    • “Because of their complexity, multigene testing is ideally offered in the context of professional genetic expertise for pre- and post-test counseling.”
    • “Testing of an individual without a cancer diagnosis should only be considered when an appropriate affected family member is unavailable for testing”.
    • “When more than one gene can explain an inherited cancer syndrome, then multi-gene testing may be more efficient and/or cost effective.” As commercially available tests differ in the specific genes analyzed (as well as classification of variants and many other factors), choosing the specific laboratory and test panel is important.” “Multi-gene testing can include “intermediate” penetrant (moderate-risk) genes. For many of these genes, there is limited data on the degree of cancer risk and there are no clear guidelines on risk management for carriers of mutations. Not all genes included on available multi-gene tests are necessarily clinically actionable.” If a moderate risk gene mutation is identified, “gene carriers should be encouraged to participate in clinical trials or genetic registries”.
    • “Mutations in many breast cancer susceptibility genes involved in DNA repair may be associated with the rare autosomal recessive condition, Fanconi anemia.” Therefore, multi-gene testing may unexpectedly reveal that an individual and their family are at an increased risk for this condition.
    • “There is an increased likelihood of finding variants of unknown significance when testing for mutations in multiple genes.”
  • Genetic/Familial High-Risk Assessment: Breast and Ovarian and Genetic/Familial High-Risk Assessment: Colorectal are currently the only cancer-specific NCCN guidelines that address the use of multi-gene panels.
  • The American College of Medical Genetics has a policy statement that offers general guidance on the clinical application of large-scale sequencing focusing primarily on whole exome and whole genome testing. However, some of the recommendations regarding counseling around unexpected results and variants of unknown significance and minimum requirements for reporting apply to many applications of NGS sequencing applications.

Place of Service: Outpatient

Hereditary cancer syndrome multigene panels are typically outpatient procedures which are only eligible for coverage as inpatient procedures in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.


The policy position applies to all commercial lines of business


Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

A network provider cannot bill the member for the non-covered service.

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