Medical Policy Update

Blue Cross and Blue Shield of Nebraska is proud to work with our provider network to serve your patients, our members. We are updating several medical policies. Please review the changes and effective dates outlined here:

Genetic Testing

Oct. 2, 2024

Revised Medical Policies

Medical Policy V.59 Hereditary Cancer Susceptibility Syndromes

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

Hereditary Breast Cancer Susceptibility Panels
A hereditary breast cancer susceptibility panel includes genes that are associated with inherited susceptibility to breast cancer.

  1. Genetic testing using a hereditary breast cancer susceptibility panel (81162, 81163, 81164, 81165, 81166, 81167, 81216, 81307, 81321, 81351, 81432, 81433, 0129U) is 
    considered medically necessary when:
    1. The member meets BRCA1 and BRCA2 Sequencing and Deletion/Duplication analysis, AND
    2. The panel includes, at a minimum, sequencing of the following genes: BRCA1, BRCA2.
  2. Genetic testing using a STAT hereditary breast cancer panel (81162, 81163, 81164, 81165, 81166, 81167, 81216) is considered medically necessary when:
    A. The member meets any of the above criteria, AND
    B. The member requires a rapid turn-around-time for decision making related to surgical interventions and treatment.

Genetic testing using a hereditary breast cancer susceptibility panel (81162, 81163, 81164, 81165, 81166, 81167, 81216, 81307, 81321, 81351, 81432, 81433, 0129U) is considered investigational for all other indications.

Hereditary Neuroendocrine Cancer Susceptibility Panels
A hereditary neuroendocrine cancer susceptibility panel is one that includes genes that are associated with inherited susceptibility to a neuroendocrine cancer.

  1. Genetic testing using a hereditary neuroendocrine cancer susceptibility panel (81437, 81438) is considered medically necessary when:
    1. The member has a diagnosis of at least one of the following:
      1. Adrenocortical carcinoma, OR
      2. Paraganglioma/pheochromocytoma, OR
      3. Parathyroid adenoma or primary hyperparathyroidism before age 30, OR
      4. Multiple parathyroid adenomas, OR
      5. Multigland hyperplasia without obvious secondary cause, OR
      6. Recurrent primary hyperparathyroidism, OR
      7. Gastrinoma, OR
      8. Duodenal or pancreatic neuroendocrine tumor, OR
      9. A first-degree relative meeting any of the above criteria, but is not available for testing, OR
    2. The member meets criteria for MEN1 sequencing and/or deletion/duplication analysis, OR
    3. The member meets criteria for RET sequencing and/or deletion duplication analysis.
  2. Genetic testing using a hereditary neuroendocrine cancer susceptibility panel (81437, 81438) is considered investigational for all other indications.

NOTE: If a multigene cancer panel is performed, the appropriate panel code should be used

BAP1 Sequencing and/or Deletion/Duplication Analysis

  1. BAP1 sequencing and/or deletion/duplication analysis (81479) for BAP1-tumor predisposition syndrome is considered medically necessary when:
    1. The member has a personal history of:
      1. Two or more of the following:
        1. BAP1-inactivated melanocytic tumors (aka atypical spitz tumor), OR
        2. Uveal melanoma, OR
        3. Malignant mesothelioma, OR
        4. Renal cell carcinoma, OR
        5. Hepatocellular carcinoma, OR
        6. Cholangiocarcinoma, OR
        7. Meningioma, OR
      2. One of the tumors/cancers listed in the criteria A.1., AND
        1. A cutaneous melanoma, OR
        2. A basal cell carcinoma, OR
      3. One of the tumors/cancers listed in the criteria A.1., AND
        1. A first- or second-degree relative with any of the following tumors/cancers:
          1. BAP1-inactivated melanocytic tumors (aka atypical spitz tumor), OR
          2. Uveal melanoma, OR
          3. Malignant mesothelioma, OR
          4. Renal cell carcinoma, OR
          5. Hepatocellular carcinoma, OR
          6. Cholangiocarcinoma, OR
          7. Meningioma, OR
          8. Cutaneous melanoma, OR
          9. Basal cell carcinoma, OR
      4. Both of the following:
        1. A diagnosis of:
          1. Cutaneous melanoma, OR
          2. Basal cell carcinoma, AND
        2. A first- or second-degree relative with any of the following tumors/cancer:
          1. BAP1-inactivated melanocytic tumors (aka atypical spitz tumor), OR
          2. Uveal melanoma, OR
          3. Malignant mesothelioma, OR
          4. Renal cell carcinoma, OR
          5. Hepatocellular carcinoma, OR
          6. Cholangiocarcinoma, OR
          7. Meningioma.
  2. BAP1 sequencing and/or deletion/duplication analysis (81479) for BAP1-tumor predisposition syndrome is considered investigational for all other indications.

SMAD4 and/or BMPR1A Sequencing and/or Deletion/Duplication Analysis

  1. SMAD4 and/or BMPR1A sequencing and/or deletion/duplication analysis (81405, 81406, 81479) for juvenile polyposis syndrome (JPS) is considered medically necessary when:
    1. The member has 5 or more juvenile polyps in the colon, OR
    2. The member has multiple juvenile polyps throughout the gastrointestinal tract, OR
    3. The member has a family history of JPS.
  2. SMAD4 and/or BMPR1A sequencing and/or deletion/duplication analysis (81405, 81406, 81479) for juvenile polyposis syndrome (JPS) is considered investigational for all other indications.

MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 Sequencing and/or Deletion/Duplication Analysis

  1. MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 sequencing and/or deletion/duplication analysis (81404, 81405, 81406, 81479) for hereditary paraganglioma/pheochromocytoma syndrome (PGL/PCC) is considered medically necessary when:
    1. The member has a diagnosis of one or more of the following:
      1. Pheochromocytoma, OR
      2. Paraganglioma, OR
      3. Clear cell renal cell cancer, OR
      4. Gastrointestinal stromal tumor (GIST), OR
    2. The member has a close relative with paraganglioma or pheochromocytoma.
  2. MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 sequencing and/or deletion/duplication (81404, 81405, 81406, 81479) for hereditary paraganglioma/pheochromocytoma syndrome (PGL/PCC) is considered investigational for all other indications.
Medical Policy V.60 Genetic Testing: Molecular Analysis of Solid Tumors and Hematologic Malignancviesv

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

HLA Typing for Transplantation

  1. HLA typing for transplantation (81370, 81371, 81372, 81373, 81376, 81378, 81379, 81380, 81382) is considered medically necessary when the member meets the following:
    1. The member is being considered for any of the following:
      1. Recipient of bone marrow transplantation, OR 
      2. Donor for bone marrow transplantation, OR
      3. Recipient of solid organ transplantation, OR
      4. Donor for solid organ transplantation.
  2. HLA typing for transplantation (81370, 81371, 81372, 81373, 81376, 81378, 81379, 81380, 81382) is considered investigational for all other indications.

HPV-Related Solid Tumor Minimal Residual Disease (MRD) Testing 

  1. Minimal residual disease analysis for HPV-related head and neck cancers using cell-free DNA (0356U) is medically necessary when: 
    1. The member has a personal history of HPV-driven oropharyngeal cancer, AND
    2. The identification of recurrence or progression of disease will require a change in management, AND
    3. The member is not undergoing concurrent surveillance or monitoring for recurrence or progression by any other method, AND
    4. The member meets one of the following:
      1. The member is currently being treated for HPV-driven oropharyngeal cancer, AND
        1. The test has not previously been done for this episode of cancer, OR
      2. The member is not currently being treated for HPV-driven oropharyngeal cancer, AND
        1. The test has not been done in the past 12 months. 
  2. Minimal residual disease analysis (0356U) using tumor tissue from HPV-related head and neck cancers is considered investigational for all other indications.

Tumor Matational Burden (TMB) 

  1. Tumor mutational burden (TMB) testing (81479) is considered medically necessary when:
    1. The member has a diagnosis of:
      1. Recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer, 
        AND
      2. The member has had progression of the cancer following prior treatment, AND
      3. The member has no remaining satisfactory treatment options, AND
      4. The member does not have central nervous system cancer. 
         
  1. Use of an adjustable cranial orthosis as a treatment of persistent plagiocephaly or brachycephaly without synostosis may be considered medically necessary when all of the following conditions have been met:
    • the individual is between 3 and 18 months old
    • documented failure of conservative therapy (repositioning and physical therapy) of at least 2 months duration
    • the individual has a cephalic index that is at least two standard deviations above or below the mean for the appropriate gender and age.
       
Medical Policy: V.61 Oncology: Circulating Tumor DNA and Circulating Tumor Cells (Liquid Biopsy)

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

Circulating Tumor Cell Tests
AR-V7 Circulating Tumor Cells (CTC) Analysis

  1. AR-V7 circulating tumor cells (CTC) analysis (81479) is considered medically necessary when:
    1. The member has a diagnosis of metastatic castration-resistant prostate cancer, AND
    2. Tissue-based testing is not feasible for the member, AND
    3. The test is ordered only once during the current cancer diagnosis, AND
    4. The member has at least one of the following:
      1. Newly metastatic cancer, OR
      2. Signs of clinical, radiological or pathologic disease progression.
  2. AR-V7 circulating tumor cells (CTC) analysis (81479) is considered investigational for all other indications.
Medical Policy: V.63 Genetic Testing: Hematologic Conditions (Non-Cancerous)

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

Inherited Thrombophilia
Factor V Leiden (F5) and Prothrombin (F2) Variant Analysis for Inherited Thrombophilia

  1. F5 (81241) and F2 (81240) variant analysis to confirm or establish a diagnosis of an inherited thrombophilia is considered medically necessary when:
    1. The member had a venous thromboembolism (VTE) that meets at least one of the following:
      1. Provoked by a nonsurgical major transient risk factor, OR
      2. Provoked by pregnancy or postpartum, OR
      3. Provoked by combination oral contraceptive use, OR
    2. The member is planning to discontinue anticoagulation after venous thromboembolism (VTE), AND
      1. The member has a history of one of the following:
        1. Cerebral venous thrombosis, OR
        2. Splanchnic venous thrombosis, OR
    3. The member has a minor provoking risk factor for VTE (e.g., immobility, minor injury, illness, infection), AND
      1. The member has two first- or second-degree relatives with VTE, OR
      2. The member meets both of the following:
        1. At least one of the relatives had VTE under age 50, AND
          1. The relative’s thrombophilia status is unknown, OR
    4. The member is a female planning a pregnancy, AND
      1. Has a first- or second-degree relative who is known to be homozygous for factor V Leiden, OR
      2. Has a first- or second-degree relative who is known to be a compound heterozygote for factor V Leiden and prothrombin (F2) mutation, OR
    5. The member is receiving systemic cancer treatment, AND
      1. Does not have a personal history of VTE, AND
      2. Has a first-degree relative with VTE.
  2. F5 (81241) and F2 (81240) variant analysis to confirm or establish a diagnosis of an inheritedthrombophilia is considered investigational for all other indications, including:
    1. Fetal loss or adverse pregnancy outcomes (examples: placental abruption, fetal growth restriction, or preeclampsia).
Medical Policy: V.65 Genetic Testing: Epilepsy, Neurodegenerative and Neuromuscular Disorders

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

Alzheimer Disease
PSEN1, PSEN2, and APP Sequencing and/or Deletion/Duplication Analysis

  1. PSEN1 (81405, 81479), PSEN2 (81406, 81479), and/or APP (81406, 81479) sequencing and/or deletion/duplication analysis to establish a diagnosis or determine future risk to develop early-onset Alzheimer disease (diagnosed before age 65 years) is considered medically necessary when:
    1. The member is 18 years of age or older, AND
    2. The member is asymptomatic*, AND
      1. Has a family history of dementia that is consistent with an autosomal dominant pattern of inheritance, AND
        • Has at least one relative with a history of early-onset Alzheimer disease (diagnosed before age 65 years), OR
    3. The member is symptomatic with dementia, AND
      1. Was diagnosed with dementia at 65 years of age or younger, AND
        • Has a close relative diagnosed with dementia, OR
        • Has an unknown family history (e.g., adoption), OR
      2. Was diagnosed with dementia at 66 years of age or older, AND
        • Has a family history of dementia that is consistent with an autosomal dominant pattern of inheritance, AND
        • Has at least one close relative who was diagnosed with dementia at 65 years of age or younger.
  2. Genetic testing for Alzheimer’s disease via other genes is considered investigational.**
  3. PSEN1 (81405, 81479), PSEN2 (81406, 81479), and/or APP (81406, 81479) sequencing and/or deletion/duplication analysis to establish the diagnosis or determine future risk to develop early-onset Alzheimer disease (diagnosed before age 65 years) is considered investigational for all other indications

NOTE: Predictive testing should only be performed in the setting and context of thorough pre- and post-test counseling
NOTE: Please see clinical guidelines “APOE Variant Analysis for Alzheimer’s Disease” for coverage 
criteria for APOE testing

Huntington's DISEASE
HTT Repeat Analysis

  1. HTT repeat analysis to establish a diagnosis or for predictive testing of Huntington’s disease (HD) (81271, 81274) is considered medically necessary when:
    1. The member displays clinical features of Huntington’s disease (i.e., progressive motor disability featuring chorea, where voluntary movement may also be affected), OR
    2. The member has a clinical diagnosis of Huntington’s disease, OR
    3. The member is undergoing predictive testing*, AND
      1. The member is presymptomatic/asymptomatic, AND
      2. The member is 18 years of age or older, AND
        1. The member has a close relative with CAG trinucleotide repeat expansion of 27 or more in HTT, OR
        2. The member has a first-degree relative with a clinical diagnosis of HD without prior genetic testing.
  2. HTT repeat analysis to establish a diagnosis or for predictive testing of Huntington’s disease (HD) (81271, 81274) is considered investigational for all other indications.

NOTE: Predictive testing should only be performed in the setting and context of thorough pre- and post-test counseling.

Medical Policy: V.66 Genetic Testing: Cardiac Disorders

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

Familial Hypercholesterolemia (FH)
Familial Hypercholesterolemia (FH) Panels

  1. Genetic testing for familial hypercholesterolemia (FH) via multigene panel (81401, 81405, 81406, 81407, 81479) to establish or confirm a diagnosis of familial hypercholesterolemia (FH) is considered medically necessary when:
    1. The member has at least two or more elevated LDL-C measurements, including assessment after intensive lifestyle modification, AND
    2. There is no apparent secondary cause of hypercholesterolemia (e.g., hypothyroidism, diabetes, renal disease, nephrotic syndrome, liver disease, medications), AND
      1. The member is a child with LDL-C levels greater than or equal to 190 mg/dl, OR
      2. The member is a child with LDL-C levels greater than or equal to 160 mg/dl with one of the following:
        1. At least one first-degree relative with elevated LDL-C, OR
        2. At least one first-degree relative with premature CAD, OR
        3. Limited family history (e.g., adoption), OR
        4. A family history of both hypercholesterolemia and premature CAD, OR
      3. The member is an adult with LDL-C levels greater than or equal to 250 mg/dl, OR
      4. The member is an adult with LDL-C levels greater than or equal to 190 mg/dl with one of the following:
        1. At least one first-degree relative with elevated LDL-C, OR
        2. At least one first-degree relative with premature CAD, OR
        3. Limited family history (e.g. adoption), OR
      5. The member is an adult with LDL-C levels greater than or equal to 160 mg/dl with one of the following:
        1. A family history of both hypercholesterolemia and premature CAD, OR
          1. A personal history of premature CAD, OR
    3. The member is an adult with premature CAD, AND
      1. A family history of both hypercholesterolemia and premature CAD.
  2. Genetic testing for familial hypercholesterolemia (FH) via multigene panel (81401, 81405, 81406, 81407, 81479) to establish or confirm a diagnosis of familial hypercholesterolemia (FH) is considered investigational for all other indications.
Medical Policy: V.70 Genetic Testing: Lung Disorders

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

Donor-derived Cell-free DNA for Lung Transplant Rejection
Evidence-Based Donor-Derived Cell-free DNA for Lung Transplant Rejection

  1. The use of peripheral blood measurement of donor-derived cell-free DNA tests (81479) with sufficient evidence of clinical utility and validity in the management of patients after lung transplantation is considered medically necessary when:
    1. The member has undergone lung transplantation, AND
    2. The test has not been performed in the last 12 months, AND
    3. The member meets at least one of the following:
      1. The member has clinical signs of acute rejection, OR
      2. A biopsy was done and is inconclusive for rejection, OR
      3. The member is being monitored for adequate immunosuppression.
  2. The use of peripheral blood measurement of donor-derived cell-free DNA tests (81479) in the management of patients after lung transplantation is considered investigational for all other indications.
Medical Policy: V.74 Genetic Testing: General approach to Genetic Testing

Effective Date: 1/1/2025
Preauthorization Required: YES
Additional policy statement:

General Criteria for Targeted Carrier Screening
The criteria below is intended for the evaluation of genetic testing that has not been more specifically addressed by coverage criteria in another policy or another section of this policy.

Targeted carrier screening is defined as a test that screens via full gene sequencing or targeted mutation analysis for a pathogenic or likely pathogenic variant in a gene associated with a specific genetic condition.

  1. Carrier screening for a genetic disorder may be considered medically necessary when:
    1. The member is considering pregnancy or is currently pregnant, AND
    2. The genetic disorder is a recessive condition with a childhood onset, AND
    3. One of the following:
      1. The member has a close relative with a known pathogenic or likely pathogenic variant associated with the disorder, OR
      2. The member’s reproductive partner is a carrier for the genetic disorder, OR
      3. The member or the member’s reproductive partner are members of a population known to have a carrier rate of 1% or higher for the genetic condition, OR
      4. The member or the member’s reproductive partner has a first- or second-degree relative who is affected with the genetic disorder.
  2. Carrier screening for a genetic disorder is considered investigational for all other indications.

Prenatal Diagnosis for Single Gene Disorders
The criteria below is intended for the evaluation of genetic testing that has not been more specifically addressed by coverage criteria in another policy or another section of this policy. State-level regulations may also necessitate review of National Guidelines, National or Local Coverage Determinations and/or FDA approvals.

  1. Prenatal diagnosis for single-gene disorders via amniocentesis, CVS (chorionic villus sampling), or PUBS (percutaneous umbilical blood sampling), may be considered medically necessary when:
    1. The member meets any of the following:
      1. At least one biological parent has a known pathogenic variant for an autosomal dominant condition, OR
      2. Both biological parents are known carriers of an autosomal recessive condition, OR
      3. One biological parent is suspected or known to be a carrier of an X-linked condition, OR
      4. The member has a history of a previous child with a genetic condition and the member is suspected to have germline mosaicism, AND
    2. The natural history of the disease is well-understood, and there is a high likelihood that the disease has high morbidity, AND
    3. The genetic test has adequate sensitivity and specificity to guide clinical decision making and residual risk is understood.
  2. Prenatal diagnosis for single-gene disorders via amniocentesis, CVS, or PUBS, for adult onset single-gene disorders (examples: hereditary cancer syndromes such as BRCA1/2, etc.) is considered not medically necessary.
  3. Prenatal diagnosis for single-gene disorders, via amniocentesis, CVS, or PUBS, is considered investigational for variants of unknown significance (VUS).
  4. Prenatal diagnosis for single-gene disorders, via amniocentesis, CVS, or PUBS, is considered investigational for all other indications.

General Criteria for Oncology Algorithmic Tests
The criteria below is intended for the evaluation of genetic testing that has not been more specifically addressed by coverage criteria in another policy or another section in this policy. State-level regulations may also necessitate review of National Guidelines, National or Local Coverage Determinations and/or FDA approvals.

  1. Oncology algorithmic testing* is considered medically necessary when:
    1. The member has a suspected or confirmed neoplasm and/or malignancy, AND
    2. The test has clinical validity, as demonstrated by accurately determining diagnostic, prognostic or clinical information for a disease, AND 
    3. The test has clinical utility, as demonstrated by at least one of the following:
      1. The test will determine if a particular therapeutic intervention is effective (or ineffective) in the member, or if a particular intervention may be harmful, OR
      2. The test will directly impact the member’s clinical management, OR
      3. The test will determine prognosis, OR
      4. The test will provide or refine estimates of the natural history, recurrence risk, or the predicted course of the genetic condition.
  2. Oncology algorithmic testing is considered investigational for all other indications.

General Criteria for Other Tests
The criteria below is intended for the evaluation of testing that has not been more specifically addressed by coverage criteria in another policy or another section of this policy. State-level regulations may also necessitate review of National Guidelines, National or Local Coverage Determinations and/or FDA approvals.

  1. Other tests are considered medically necessary when:
    1. The member displays relevant clinical features consistent with the intended use of the test, AND
    2. The test has clinical validity, as demonstrated by accurately determining diagnostic, prognostic or clinical information for a disease, AND 
    3. The test has clinical utility, as demonstrated by at least one of the following:
      1. The test will determine if a particular therapeutic intervention is effective (or ineffective) in the member, or if a particular intervention may be harmful, OR
      2. The test will directly impact the member’s clinical management, OR
      3. The test will determine prognosis, OR
      4. The test will provide or refine estimates of the natural history, recurrence risk, or the predicted course of the disease or genetic condition, AND
    4. Testing is being performed in a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory.
  2. Other tests are considered investigational for all other indications.
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