Medical_Policy

Highmark Commercial Medical Policy - Pennsylvania

Medical Policy:	L-195-002
Topic:	Hereditary (Germline) Testing After Tumor (Somatic) Testing
Section:	Laboratory
Effective Date:	November 13, 2017
Issue Date:	November 13, 2017
Last Reviewed:	March 2017

Most cancer is sporadic and due to the acquisition of somatic variants. In oncology, next generation sequencing (NGS) technology makes it feasible to catalog the DNA sequence variations within a person’s cancer (i.e., somatic mutation profiling). This helps define therapeutic targets and which might improve outcomes through the use of specific medications directed at those mutations. Germline variants can also be identified as an ancillary finding during primary tumor profiling to identify somatic mutations.

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.

Single-site or full-gene sequence germline tumor testing following somatic tumor analysis may be considered medically necessary when at least ONE of the following criteria is met:

The individual’s personal or family history is suggestive of a germline mutation, a specific germline variation is identified by somatic tumor testing, and the individual meets the published test-specific criteria to test for that variant; or
One of the identified variants is a highly-recurrent or founder mutation (i.e., BRCA1 c185delAG or the recurrent inversion of MSH2 seen in some families with Lynch syndrome); or
The tumor profile shows thousands of somatic variants, suggesting a germline mutation in a DNA mismatch repair gene or in the POLE proofreading domain; or
Two separate primary tumors are sequenced and both harbor the same genetic variant; or
The individual’s tumor harbors a mutation in BRCA1/2; or
Patient does not meet published criteria for germline testing, but variant(s) in genes that commonly harbor somatic mutations (including but not limited to TP53, APC, CDH1) are identified and the variant allele frequency in the tumor is at least 50%.

In individuals meeting criteria for germline DNA testing, analysis of the entire gene, as opposed to single site testing, is recommended.

Germline testing of somatic variants of uncertain significance (VUS) is considered not medically necessary.

Germline testing for asymptomatic individuals based solely on a family member’s somatic testing result is considered not medically necessary.

Resources, such as ClinVar15, should be used to determine if a pathogenic variant classification provided by germline testing laboratories is consistent with independent assessments of that variant.

Procedure Codes

81201, 81203, 81408, 81211, 81213, 81214, 81216, 81228, 81229, 81292, 81294, 81295, 81297, 81298, 81300, 81317, 81319, 81321, 81323, 81432, 81433, 81435, 81436, 81437, 81438, 81400, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 81479

Professional Statements and Societal Positions

The National Comprehensive Cancer Network (NCCN, 2017) states the following regarding germline testing following somatic tumor testing for BRCA1/2 mutations.

BRCA1/2 germline mutation testing should be performed when a BRCA1/2 mutation is detected by tumor profiling.
There have been various peer-reviewed publications that reviewed pre- and post-test considerations for germline testing following somatic tumor testing.
- Pre-test considerations:
  - Somatic tumor-only NGS testing is used to guide treatment for an affected person. The testing is not designed to elucidate a hereditary etiology. A germline variant may not be detected (due to differences in coverage in the testing, cellularity of the sample, allelic loss of the germline mutation) or may not be reported by the somatic testing laboratory.
  - Directed germline genetic testing can be ordered to identify a potential hereditary etiology for the person’s tumor. Referrals to oncology genetic counselors or other specialized healthcare providers should occur if the individual’s personal and/or family history meets established criteria to warrant a more detailed discussion.
  - Ancillary findings from somatic or germline testing may include variants in genes that cause a hereditary cancer syndrome, a nononcologic hereditary syndrome, or identify carrier status for Mendelian disease. Specific findings are dependent on specific testing performed by the laboratory.
  - Many patients undergoing somatic tumor profiling have advanced stage disease. Centers performing somatic tumor profiling should consider obtaining a surrogate individual to receive results in the event that the proband has passed away or is otherwise unable to receive the results.
- Post-test considerations:
  - Clinicians must determine the technical specifications of the laboratory used for somatic tumor profiling and determine if this includes paired germline testing. Some laboratories may not report germline variants.
  - Tumor profiling variant interpretation may differ from the variant interpretation process for germline mutations. For example, a laboratory profiling a somatic tumor may classify a certain variant as pathogenic whereas a laboratory testing a germline mutation may classify that same variant as a variant of uncertain significance (VUS).
  - Referrals to oncology genetic counselors or other specialized healthcare providers should occur if the individual’s personal and/or family history meets established criteria to warrant a more detailed discussion, regardless of somatic tumor profiling results.

Place of Service: Outpatient

Single-site or full-gene sequence germline tumor testing following somatic tumor analysis is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure 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.

Links

Link to Provider Resource Center for the Medical Policy Update

05/2017, REMINDER: Molecular and Genomic Testing

Link to References

Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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