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. 1, 2025
Medical Policy: V.59 Oncology testing: Hereditary cancer

Effective Date:  07/01/2025
Effective Date: 1/1/2026
Preauthorization Required: Yes

CDH1 Sequencing and/or Deletion/Duplication Analysis

  1. CDH1 sequencing and/or deletion/duplication analysis for Hereditary Diffuse Gastric Cancer (aka gastric signet ring cell carcinoma) is considered medically necessary when:
    1. The member is 18 years or older, AND
    2. The member meets at least one of the following criteria:
      1. Diffuse gastric cancer (aka gastric signet ring cell carcinoma, or SRCC) at any age, OR
      2. Lobular breast cancer at any age with a personal or family history of diffuse gastric cancer/gastric SRCC, OR
      3. A close relative with two or more gastric cancer diagnoses, AND
        1. One case was diagnosed at or before age 50, OR
        2. One case was confirmed to be diffuse gastric cancer/SRCC, OR
      4. A close relative with a history of diffuse gastric cancer/SRCC, AND
        1. A family history of Maori ancestry, OR
        2. A family history of cleft lip/palate.
  2. CDH1 sequencing and/or deletion/duplication analysis for Hereditary Diffuse Gastric Cancer (aka, gastric signet ring cell carcinoma) is considered investigational for all other indications.
BAP1 Sequencing and/or Deletion/Duplication Analysis
  1. BAP1 sequencing and/or deletion/duplication analysis 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. Cholangiocarcinoma, OR
        6. 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. Cholangiocarcinoma, OR
          6. Meningioma, OR
          7. Cutaneous melanoma, OR
          8. 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. Cholangiocarcinoma, OR
          6. Meningioma.
  2. BAP1 sequencing and/or deletion/duplication analysis for BAP1-tumor predisposition syndrome is considered investigational for all other indications.
Hereditary Polyposis Susceptibility Panels
A hereditary polyposis panel includes genes that are associated with inherited susceptibility to colon polyposis.
  1. I. Genetic testing using a hereditary polyposis susceptibility panel is considered medically necessary when the member meets BOTH A and B:
    1. The member has a history of any of the following:
      1. 10 or more cumulative adenomas, OR
      2. Congenital hypertrophy of the retinal pigment epithelium (CHRPE), OR
      3. Desmoid tumor, OR
      4. Hepatoblastoma, OR
      5. Cribriform-morular variant of papillary thyroid cancer, OR
      6. A clinical diagnosis of serrated polyposis syndrome, with at least some adenomas, based on one of the following:
        1. 5 or more serrated polyps proximal to the rectum, all being 5mm or greater in size and at least 2 being 10mm or greater in size, OR
        2. More than 20 serrated polyps of any size distributed throughout the large bowel, with at least 5 or more being proximal to the rectum, AND
    2. The panel includes, at a minimum, sequencing of the following genes: APC and MUTYH.
  2. Genetic testing using a hereditary polyposis susceptibility panel is considered investigational for all other indications.
  3. mRNA sequencing analysis in genes associated with polyposis syndromes for the interpretation of variants of unknown significance is considered investigational because it is typically either considered an existing component of the genetic testing process for quality assurance or follow up testing without proven utility.

Hereditary Breast and/or Ovarian Cancer Susceptibility Panels
A hereditary breast and/or ovarian cancer susceptibility panel includes genes that are associated with an inherited susceptibility to breast cancer, ovarian cancer, or both.

  1. Genetic testing using a hereditary breast and/or ovarian cancer susceptibility panel is considered medically necessary when:
    1. The panel includes, at a minimum, the following genes: BRCA1, BRCA2, AND
    2. The member has one of the following:
      1. The member has a personal history of breast cancer < age 65, OR
      2. The member has a personal history of ovarian cancer (including fallopian tube cancer or peritoneal cancer), OR
      3. The member has a personal history of breast cancer, AND
        1. One of the following:
          1. Ashkenazi Jewish ancestry, OR
          2. Male (sex assigned at birth), OR
          3. Triple-negative breast cancer, OR
          4. Pancreatic or ampullary cancer, OR
          5. Metastatic prostate cancer, OR
          6. High- or very-high-risk group prostate cancer, OR
          7. Multiple primary breast cancers (diagnosed synchronously or metachronously), OR
          8. The member has a close relative with any one of the following:
            1. Breast cancer diagnosed <age 50, OR
            2. Male breast cancer, OR
            3. Ovarian cancer, OR
            4. Pancreatic cancer, OR
            5. Prostate cancer that is either metastatic, intermediate-risk or high- or very-high-risk group, OR
        2. There are 3 or more total diagnoses of breast cancer and/or prostate cancer (any grade) on the same side of the family including the member with breast cancer, OR
      4. The member has a personal history of lobular breast cancer, AND
        1. A personal or family history of diffuse gastric cancer, OR
      5. The member is unaffected or the member does not have a personal history of breast cancer that meets the above criteria, AND
        1. The member has a first- or second-degree relative diagnosed with breast cancer at or before age 50 years, OR
        2. The member has a first- or second-degree relative meeting any of criteria I.B.2, I.B.3, or I.B.4, OR
        3. The member’s probability of having a BRCA1 or BRCA2 pathogenic variant is greater than 2.5% based on prior probability models (e.g., Tyrer-Cuzick, BRCApro, CanRisk), OR
      6. The member has a personal history of breast cancer, AND
        1. The member has recurrent unresectable or metastatic breast cancer and is being considered for systemic treatment using PARP inhibitors, OR
        2. The member has recurrent or metastatic breast cancer and is being considered for adjuvant treatment with Olaparib therapy.
  2. Genetic testing using a STAT hereditary breast cancer panel is considered medically necessary when:
    1. The member meets any of the above criteria, AND
    2. The member requires a rapid turn-around-time for decision making related to surgical interventions or treatment.
  3. Genetic testing using a hereditary breast and/or ovarian cancer susceptibility panel is considered investigational for all other indications.
  4. BRCA1/BRCA2 mRNA sequencing analysis in genes associated with breast and/or ovarian cancers for the interpretation of variants of unknown significance is considered investigational because it is typically either considered an existing component of the genetic testing process for quality assurance or follow up testing without proven utility.
Medical Policy: V.60 Oncology testing: Solid tumor molecular diagnostics

Effective Date: 1/1/2026
Preauthorization Required: Yes

Molecular profiling panel tests via circulating tumor DNA (CTDNA)

  1. Broad Molecular Profiling Panel Tests via Circulating Tumor DNA (ctDNA) I. Broad molecular profiling panel tests via circulating tumor DNA (ctDNA) (liquid biopsy) are considered medically necessary when:
    1. The member has a diagnosis, progression, or recurrence of one of the following:
      1. Locally advanced/metastatic pancreatic adenocarcinoma, OR
      2. Metastatic or advanced gastric cancer, OR
      3. Metastatic or advanced esophageal or esophagogastric junction cancer, OR
      4. Metastatic prostate cancer, OR
      5. Stage III or IV cutaneous melanoma, OR
      6. Metastatic colorectal cancer, OR
      7. Locally advanced or metastatic ampullary adenocarcinoma, OR
      8. Persistent or recurrent cervical cancer, OR
      9. Unresectable or metastatic biliary tract cancer, OR
      10. Suspected or confirmed histiocytic neoplasm, OR
      11. Locoregional unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine neoplasms, OR
      12. Locoregional unresectable or metastatic large or small cell neuroendocrine neoplasms, OR
      13. Locoregional unresectable or metastatic mixed neuroendocrine-non-neuroendocrine neoplasm, OR
      14. Suspected metastatic malignancy of unknown primary with initial determination of histology, OR
      15. Recurrent ovarian, fallopian tube or primary peritoneal cancer, AND
      16. At least one of the following:
        1. The member is medically unfit for invasive tissue sampling (biopsy), OR
        2. Biopsy was performed, but material was insufficient for molecular analysis, OR
        3. Biopsy was performed, but molecular analysis was not able to be completely assessed on tissue due to availability of testing methodologies, OR
        4. Biopsy is not possible due to location of the tumor, OR
    2. The member is being evaluated at diagnosis, progression, or recurrence of one of the following:
      1. Recurrent or stage IV breast cancer, OR
      2. Suspected or proven metastatic rectal cancer, OR
      3. Suspected or proven metastatic colon cancer, OR
      4. Locally advanced or metastatic lung adenocarcinoma, OR
      5. Locally advanced or metastatic large cell lung carcinoma, OR
      6. Locally advanced or metastatic squamous cell lung carcinoma, OR
      7. Locally advanced or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS),
    3. The member has a diagnosis of metastatic prostate cancer, AND
      1. The member is undergoing initial workup, OR
      2. There is biochemical or radiologic evidence of recurrence or progression as demonstrated by either of the following:
        1. Prostate specific antigen (PSA) is not undetectable, OR
        2. There is radiographic progression.
  2. Broad molecular profiling panel tests via circulating tumor DNA (ctDNA) performed simultaneously with solid tumor tissue testing is considered medically necessary when the member has one of the following diagnoses:
    1. Lung adenocarcinoma, OR
    2. Large cell lung carcinoma, OR
    3. Squamous cell lung carcinoma, OR
      1. Non-small cell lung cancer (NSCLC) not otherwise specified (NOS).
  3. Broad molecular profiling panel tests via circulating tumor DNA (ctDNA) are considered investigational for all other indications, including being performed simultaneously with solid tumor tissue testing for tumor types other than those described above.
Medical Policy: V.62 Specialty testing: Multisystem genetic conditions

Effective Date: 1/1/2026
Preauthorization Required: Yes

Combined Mitochondrial DNA Analysis and Exome Sequencing

  1. Combined1 mitochondrial DNA sequence and deletion/duplication analysis and exome sequencing is considered medically necessary when:
    1. The member meets clinical criteria for Mitochondrial Genome Sequencing, Deletion/Duplication, and/or Nuclear Gene Panel, AND
    2. The member meets clinical criteria for Standard Exome Sequencing.
  2. Combined mitochondrial DNA sequence and deletion/duplication analysis and exome sequencing is considered investigational for all other indications.

1This refers to tests for which exome sequencing (ES) and mitochondrial DNA (mtDNA) sequencing cannot be performed or billed separately (specifically 0214U and 0215U). Refer to Mitochondrial Genome Sequencing, Deletion/Duplication, and/or Nuclear Gene Panel or Standard Exome Sequencing for individual criteria that is billed separately.

Medical Policy: V.80 Specialty testing: Transplant

Effective Date: 1/1/2026
Preauthorization Required: Yes

Evidence-Based Donor-Derived Cell-free DNA for Solid Organ Transplant Rejection

  1. The use of peripheral blood measurement of donor-derived cell-free DNA in the management of patients after solid organ transplantation is considered medically necessary when:
    1. Peripheral blood measurement of donor-derived cell-free DNA has not been performed in the past twelve months, AND
    2. The member meets one of the following:
      1. The member has undergone a heart transplantation, AND
        1. The test is Allosure or Prospera, OR
      2. The member has undergone a kidney transplantation, AND
        1. The test is Allosure, Prospera, Viracor TRAC Kidney dd-cfDNA, VitaGraft Kidney 2.0, VitaGraft Kidney Baseline, or VitaGraft Kidney Subsequent, AND
          1. The member meets at least one of the following:
            1. The member has clinical signs of acute rejection, OR
            2. A biopsy was done to check for signs of acute rejection and is inconclusive, OR
            3. The member is being monitored for adequate immunosuppression, OR
      3. The member has undergone a lung transplantation, AND
        1. The test is Allosure or Prospera, AND
          1. The member meets at least one of the following:
            1. The member has clinical signs of acute rejection, OR
            2. A biopsy was done to check for signs of acute rejection and is inconclusive, OR
            3. The member is being monitored for adequate immunosuppression.
  2. The use of peripheral blood measurement of donor-derived cell-free DNA in the management of patients after solid organ transplantation is considered investigational for all other indications.
Medical Policy: V.82 Oncology testing: Hematologic malignancy molecular diagnostics

Effective Date: 1/1/2026
Preauthorization Required: Yes

Tumor Specific BCR-ABL1 FISH, Qualitative, and Quantitative Tests

  1. Tumor specific BCR-ABL1 FISH, qualitative, or quantitative tests in hematologic malignancies are considered medically necessary when:
    1. The member is suspected to have a myeloproliferative neoplasm (MPN), OR
    2. The member is undergoing diagnostic workup for:
      1. Acute lymphoblastic leukemia (ALL), OR
      2. Acute myeloid leukemia (AML), OR
      3. Chronic myeloid leukemia (CML), OR
      4. Lymphoblastic leukemia, OR
    3. The member is undergoing monitoring of disease progression or for minimal residual disease (MRD) monitoring using a quantitative test only for:
      1. Acute lymphoblastic leukemia (ALL), OR
      2. Acute myeloid leukemia (AML), OR
      3. Chronic myeloid leukemia (CML), AND
        1. The member’s provider is considering discontinuation of or has already discontinued use of TKI therapy.

Tumor Specific KIT Variant Analysis for Hematologic Malignancies

  1. Tumor specific KIT variant analysis in hematologic malignancies is considered medically necessary when:
    1. The member is being evaluated for systemic mastocytosis, OR
    2. The member has a diagnosis of acute myeloid leukemia (AML).

NTRK Fusion Analysis Panel for Hematologic Malignancies

  1. NTRK 1/2/3 fusion analysis panel via fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC) in hematologic malignancies is considered medically necessary when:
    1. The member has a diagnosis of any of the following cancers at any stage:
      1. Acute lymphoblastic leukemia (ALL).
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