This document addresses gene mutation testing to determine whether an individual is at risk for the development of malignant tumors (including but not limited to breast, colon, lung, pancreatic and ovarian cancers) and to guide cancer management or targeted cancer therapy in individuals with malignant conditions. This document also addresses the use of circulating tumor DNA testing to assess gene mutations.

Note(s):

• This document does not address gene panel testing (defined by five or more genes or gene variants tested on the same day on the same member by the same rendering provider). For information on these tests, please see the following:
  • GENE.00052 Whole Genome Sequencing, Whole Exome Sequencing, Gene Panels, and Molecular Profiling
• This document does not address circulating tumor cell (CTC) tests. For information on these tests, please see LAB.00015 Detection of Circulating Tumor Cells.
• This document does not provide coverage criteria for drugs including but not limited to chemotherapeutic agents or associated therapeutic products.
• For information on genetic testing for inherited diseases (including preconception or prenatal genetic testing and testing for germline genetic diseases), see CG-GENE-13 Genetic Testing for Inherited Diseases.
• When an individual genetic test is addressed in a separate medical policy or clinical utilization management guideline (CUMG), that policy or CUMG applies. For additional information, please see the following related documents:
  • CG-GENE-15 Genetic Testing for Lynch Syndrome, Familial Adenomatous Polyposis (FAP), Attenuated FAP and MYH-associated Polyposis
  • CG-GENE-16 BRCA Genetic Testing
  • CG-GENE-19 Measurable Residual Disease Assessment in Lymphoid Cancers Using Next Generation Sequencing
  • GENE.00025 Proteogenomic Testing for the Evaluation of Malignancies
  • GENE.00052 Whole Genome Sequencing, Whole Exome Sequencing, Gene Panels, and Molecular Profiling

Clinical Indications

Medically Necessary:

1. Gene Mutation Testing for Cancer Susceptibility (See Table A below)
   Gene mutation testing for cancer susceptibility is considered medically necessary when all of the following criteria are met:
   1. The genetic disorder is associated with a potentially significant cancer; and
   2. The risk of the significant cancer associated with the genetic disorder cannot be identified through biochemical or other testing; and
   3. A specific mutation, or set of mutations, has been established in the scientific literature to be reliably associated with the risk of developing malignancy; and
   4. The results of the genetic test may impact the medical management (for example, surveillance; life-style) of the individual; and
   5. Genetic counseling, which encompasses all of the following components, has been performed:
      1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
      2. Education about inheritance, genetic testing, disease management, prevention and resources; and
      3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
      4. Counseling for the psychological aspects of genetic testing.
2. Gene Mutation Testing to Guide Cancer Management or Targeted Cancer Therapy (See Table B below)
   Gene mutation testing used to identify individuals for cancer management or to guide targeted cancer therapy is considered medically necessary when all of the following criteria are met:
   1. The individual is a candidate for treatment (for example, targeted therapy using a pharmaceutical or biologic treatment) or other cancer management strategies, and the mutation status of a specific gene, or set of mutations, is required prior to initiating, or as part of treatment; and
   2. A specific mutation, or set of mutations, has been established in the scientific literature to identify those most likely to benefit from treatment.
3. Circulating Tumor DNA (Liquid Biopsy) to Guide Cancer Management or Targeted Cancer Therapy (See Table C below)
   Use of a circulating tumor DNA (ctDNA) test for cancer management or to guide targeted cancer therapy in individuals with solid tumors is considered medically necessary when the mutation(s) meets criteria “B” above and when formalin-fixed paraffin-embedded tumor tissue (FFPET) is inadequate in quality or quantity or is unavailable for testing.

Note: For information on circulating tumor DNA panel testing (defined by five or more genes or gene variants tested on the same day on the same member by the same rendering provider), see GENE.00052 Whole Genome Sequencing, Whole Exome Sequencing, Gene Panels, and Molecular Profiling.

Not Medically Necessary:

1. Gene Mutation Testing for Cancer Susceptibility
   Gene mutation testing for cancer susceptibility is considered not medically necessary in individuals not meeting all of the Section A criteria above.
2. Gene Mutation Testing to Guide Cancer Management or Targeted Cancer Therapy
   Gene mutation testing used to identify individuals for cancer management or to guide targeted cancer therapy is considered not medically necessary when the medically necessary criteria in Section B above are not met.
3. Circulating Tumor DNA (Liquid Biopsy) to Guide Cancer Management or Targeted Cancer Therapy
   Use of a circulating tumor DNA (ctDNA) test for cancer management or to guide targeted cancer therapy in individuals with solid tumors is considered not medically necessary when the medically necessary criteria in Section C above is not met, including to detect the recurrence of a solid tumor, including colorectal cancer, and to test for solid tumor cancer susceptibility.