Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

The molecular analysis of solid tumors and hematologic malignancies aims to identify somatic oncogenic mutations in cancer.  These mutations, often called “driver” mutations, are becoming increasingly useful for targeted therapy selection, and may give insight into prognosis and treatment response in a subset of cancers.  In addition, molecular analysis of solid tumors and hematologic malignancies, in particular, can also aid in making a diagnosis of a specific type of malignancy.  For solid tumors, molecular analysis can be performed via direct testing of the tumor (which is addressed in this policy) or via circulating tumor DNA or circulating tumor cells (CTCs) (see Other Related Policies).  For hematologic malignancies, molecular analysis can be performed on blood samples or bone marrow biopsy samples.

For individuals with advanced cancer, somatic comprehensive genomic profiling offers the potential to evaluate a large number of genetic markers in the cancer simultaneously in order to provide potential treatment options beyond the current standard of care.

While the primary goal of the molecular analysis of solid tumors and hematologic malignancies is to identify biomarkers that diagnose or to give prognostic and treatment selection information, this testing also has the potential to uncover clinically relevant germline variations that are associated with a hereditary cancer susceptibility syndrome, and other conditions, if confirmed to be present in the germline. Current tumor testing strategies include tumor-only testing, tumor-normal paired testing with germline variant subtraction, and tumor-normal paired testing with explicit analysis of a group of genes associated with germline cancer predisposition. This is an evolving area and clear guidelines around the optimal approach for identification and reporting of the presumed germline pathogenic variants (PGPVs) are emerging.

Molecular Profiling Panel Testing of Solid Tumors and Hematologic Malignancies

Comprehensive Molecular Profiling Panels for Solid Tumors

1. It is the policy of health plans affiliated with Centene Corporation® that comprehensive molecular profiling panels for solid tumors (0037U, 0048U, 0211U, 81445, 81455) is considered medically necessary when meeting all of the following:
   1. The member/enrollee has recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer,
   2. The member/enrollee is seeking further cancer treatment (e.g., therapeutic chemotherapy),
   3. One of the following:
      1. The member/enrollee has not had previous comprehensive solid tumor molecular profiling for the primary cancer diagnosis,
      2. The member/enrollee HAS had previous comprehensive solid tumor molecular profiling for the primary cancer diagnosis, and has a new primary cancer diagnosis for which this testing is being ordered.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support comprehensive molecular profiling panels for solid tumors (0037U, 0048U, 0211U, 81445, 81455) for all other indications.

Comprehensive Molecular Profiling Panels for Hematologic Malignancies and Myeloid Malignancy Panels

1. It is the policy of health plans affiliated with Centene Corporation® that comprehensive molecular profiling panels for hematologic malignancies and myeloid malignancy panels in bone marrow or peripheral blood (81450, 81455) is considered medically necessary when meeting any of the following:
   1. The member/enrollee has a suspected or confirmed diagnosis of acute myeloid leukemia (AML),
   2. The member/enrollee has persistent cytopenia(s) (at least 4-6 months) and a myelodysplastic syndrome is suspected or has been newly diagnosed,
      1. Other causes of cytopenia(s) have been ruled out, including:

a)    Nutritional anemias (e.g., iron deficiency anemia, folate deficiency anemia, vitamin B12 deficiency anemia),

b)    Thyroid disease,

c)    Drug-induced cytopenia,

d)    Viral infection (e.g., HIV),

1. The member/enrollee was suspected to have a myeloproliferative neoplasm, and both of the following:
   1. JAK2, CALR, MPN, and BCR/ABL analysis were previously performed and the results were negative,
   2. Clinical suspicion for a myeloid neoplasm remains high,
2. The member/enrollee has a diagnosis of chronic myelogenous leukemia, and both of the following:
   1. There has been progression to accelerated phase or blast phase,
   2. BCR-ABL1 kinase domain mutation analysis has been performed and the results were negative.
1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support comprehensive molecular profiling panels for hematologic malignancies and myeloid malignancy panels in bone marrow or peripheral blood (81450, 81455) for all other indications.

Note: If a multigene panel is performed, appropriate panel codes should be used. 

Colorectal Cancer Focused Molecular Profiling Panels

1. It is the policy of health plans affiliated with Centene Corporation® that colorectal cancer focused molecular profiling panels (0111U, 81301, 81445) in solid tumors is considered medically necessary when meeting all of the following:
   1. The member/enrollee has suspected or proven metastatic, synchronous or metachronous colorectal cancer,
   2. The member/enrollee is seeking further cancer treatment (e.g., therapeutic chemotherapy,
   3. One of the following:
      1. The member/enrollee has not had previous somatic testing via a multigene cancer panel for the same primary diagnosis of colorectal cancer,
      2. The member/enrollee HAS had previous somatic testing via a multigene cancer panel for a primary colorectal cancer diagnosis, and has a new primary colorectal cancer diagnosis for which this testing is being ordered.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support colorectal cancer-focused molecular profiling panels (0111U, 81301, 81445) for all other indications.

Note: If a panel is performed, appropriate panel codes should be used.

Lung Cancer Focused Molecular Profiling Panels

1. It is the policy of health plans affiliated with Centene Corporation® that lung cancer focused molecular profiling panels (0022U, 81445) is considered medically necessary when meeting all of the following:
   1. The member/enrollee has a diagnosis of any of the following:
      1. Advanced (stage IIIb or higher) or metastatic lung adenocarcinoma,
      2. Advanced (stage IIIb or higher) or metastatic large cell lung carcinoma,
      3. Advanced (stage IIIb or higher) or metastatic squamous cell lung carcinoma,
      4. Advanced (stage IIIb or higher) or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS),
   2. The member/enrollee is seeking further cancer treatment (e.g., therapeutic chemotherapy),
   3. One of the following:
      1. The member/enrollee has not had previous somatic testing via a multigene cancer panel for the same primary lung cancer diagnosis,
      2. The member/enrollee HAS had previous somatic testing via a multigene cancer panel for a primary lung cancer diagnosis, and has a new primary lung cancer diagnosis for which this testing is being ordered.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support lung cancer-focused molecular profiling panels (81445, 0022U) for all other indications.

Note: If a panel is performed, appropriate panel codes should be used.

Cutaneous Melanoma Focused Molecular Profiling Panels

1. It is the policy of health plans affiliated with Centene Corporation® that cutaneous melanoma focused molecular profiling panels (81210, 81273, 81311, 81403, 81404, 81445) is considered medically necessary when meeting all of the following:
   1. The member/enrollee has a new diagnosis of stage IV melanoma or has recurrent melanoma,
   2. The member/enrollee is seeking further cancer treatment (e.g. therapeutic chemotherapy),
   3. One of the following:
      1. The member/enrollee has not had previous somatic testing via a multigene cancer panel for the same primary melanoma diagnosis,
      2. The member/enrollee HAS had previous somatic testing via a multigene cancer panel for a primary melanoma diagnosis, and has a new primary melanoma diagnosis for which this testing is being ordered.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support cutaneous melanoma focused molecular profiling panels (81210, 81273, 81311, 81403, 81404, 81445) for all other indications.

Note: If a panel is performed, appropriate panel codes should be used.

Acute Myeloid Leukemia (AML) Focused Molecular Profiling Panels

1. It is the policy of health plans affiliated with Centene Corporation® that acute myeloid leukemia focused molecular profiling panels (81450) for the diagnosis or evaluation of acute myeloid leukemia (AML) is considered medically necessary when:
   1. The member/enrollee has a suspected or confirmed diagnosis of acute myeloid leukemia (AML).
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support acute myeloid leukemia focused molecular profiling panels (81450) for the diagnosis or evaluation of acute myeloid leukemia (AML) for all other indications.

Note: If a multigene panel is performed, appropriate panel codes should be used.

Myeloproliferative Neoplasms (MPNs) Molecular Profiling Panel

1. It is the policy of health plans affiliated with Centene Corporation® that myeloproliferative neoplasm (MPN) molecular profiling panel (81206, 81207, 81208, 81270, 81219, 81402, 81403) is considered medically necessary when meeting both of the following:
   1. The member/enrollee is suspected to have a myeloproliferative neoplasm (i.e., polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia),
   2. The panel does not include genes other than JAK2, CALR, MPL, and BCR/ABL1.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support myeloproliferative neoplasm (MPN) molecular profiling panel (81206, 81207, 81208, 81270, 81219, 81402, 81403) analysis for all other indications.

Single-Gene Testing Of Solid Tumors And Hematologic Malignancies

ABL1 Kinase Domain Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic ABL1 kinase domain analysis (81170) in hematologic malignancies is considered medically necessary when meeting both of the following:
   1. The member/enrollee has a diagnosis of chronic myeloid leukemia (CML) or Ph-like acute lymphoblastic leukemia (ALL),
   2. Any of the following:
      1. Initial response to TKI therapy is inadequate,
      2. Loss of response to TKI therapy,
      3. Disease progression to the accelerated or blast phase,
      4. Relapsed/refractory disease.

BCR/ABL1 Breakpoint Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic BCR/ABL1 breakpoint analysis (0016U, 0040U, 81206, 81207, 81208) in hematologic malignancies is considered medically necessary when meeting either of the following:
   1. The member/enrollee is suspected to have a myeloproliferative neoplasm (i.e., polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia),
   2. The member/enrollee is undergoing workup for or to monitor disease progression of any of the following:
      1. Acute lymphoblastic leukemia (ALL),
      2. Acute myeloid leukemia (AML),
      3. Chronic myelogenous leukemia (CML),
      4. Lymphoblastic leukemia.

BRAF Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic BRAF variant analysis (81210) in solid tumors and hematologic malignancies is considered medically necessary when meeting either of the following:
   1. The member/enrollee has a diagnosis of any of the following:
      1. Suspected or proven metastatic, synchronous or metachronous colorectal cancer,
      2. Advanced or metastatic non-small-cell lung cancer (NSCLC),
      3. Stage III or stage IV cutaneous melanoma,
      4. Anaplastic thyroid carcinoma or locally recurrent, advanced and/or metastatic papillary, follicular or Hurthle cell thyroid carcinoma,
      5. Low-grade glioma or pilocytic astrocytoma,
   2. The member/enrollee is being evaluated for:
      1. Hairy cell leukemia (for individuals without cHCL immunophenotype).

BRCA1/2 Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic BRCA1/2 variant analysis (81162, 81163, 81164, 81165, 81166, 81167, 81216) in solid tumors is considered medically necessary when:
   1. The member/enrollee has a diagnosis of one of the following:
      1. Ovarian, fallopian tube and/or primary peritoneal cancer,
      2. Metastatic prostate cancer.

CALR Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic CALR variant analysis (81219) in solid tumors or hematologic malignancies is considered medically necessary when:
   1. The member/enrollee is suspected to have a myeloproliferative neoplasm (i.e., polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia).

CEBPA Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic CEBPA variant analysis (81218) in solid tumors or hematologic malignancies is considered medically necessary when:
   1. The member/enrollee has cytogenetically normal acute myeloid leukemia (AML).

EGFR Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic EGFR variant analysis (81235) in solid tumors is considered medically necessary when:
   1. The member/enrollee has a diagnosis of any of the following:
      1. Advanced or metastatic lung adenocarcinoma,
      2. Advanced or metastatic large cell lung carcinoma,
      3. Advanced or metastatic squamous cell lung carcinoma,
      4. Advanced or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS).

FLT3 Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic FLT3 variant analysis (81245, 81246, 0023U, 0046U) in solid tumors or hematologic malignancies is considered medically necessary when meeting either of the following:
   1. The member/enrollee has suspected or confirmed acute myeloid leukemia (AML),
   2. The member/enrollee has a diagnosis of acute lymphoblastic leukemia (ALL) and previous testing for BCR-ABL1 was negative.

IDH1 and IDH2 Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic IDH1 and IDH2 variant analysis (81120, 81121) in solid tumors is considered medically necessary when:
   1. The member/enrollee has a diagnosis of a glioma.

IGHV Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic IGHV variant analysis (81261, 81262, 81263) in hematologic malignancies is considered medically necessary when:
   1. The member/enrollee has a diagnosis of any of the following:
      1. Chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL),
      2. Primary cutaneous B-cell lymphoma,
      3. Mantle cell lymphoma,
      4. Post-transplant lymphoproliferative disorder.

JAK2 Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic JAK2 variant analysis (81270, 0017U, 0027U) in solid tumors or hematologic malignancies is considered medically necessary when:
   1. The member/enrollee is suspected to have a myeloproliferative neoplasm (i.e., polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia).

KIT Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that Somatic KIT variant analysis (81272, 81273) in solid tumors or hematologic malignancies is considered medically necessary when meeting any of the following:
   1. The member/enrollee is suspected to have, or is being worked up for, systemic mastocytosis,
   2. The member/enrollee has a diagnosis of acute leukemia,
   3. The member/enrollee has stage IV cutaneous melanoma,
   4. The member/enrollee has a suspected or confirmed gastrointestinal stromal tumor (GIST).

KRAS Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic KRAS variant analysis (81275, 81276, S3713) in solid tumors is considered medically necessary when meeting either of the following:
   1. The member/enrollee has suspected or proven metastatic, synchronous or metachronous colorectal cancer,
   2. The member/enrollee is undergoing workup for metastasis non-small cell lung cancer.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support somatic KRAS variant analysis (81275, 81276, S3713) in solid tumors, as a stand alone test, in an individual with non-small cell lung cancer (NSCLC).

MGMT Promoter Methylation Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic MGMT promoter methylation analysis (81287) in solid tumors is considered medically necessary when:
   1. The member/enrollee has a high grade glioma (stage III or IV), including one of the following:
      1. Anaplastic oligodendroglioma,
      2. Anaplastic oligoastrocytoma,
      3. Anaplastic astrocytoma,
      4. Anaplastic glioma,
      5. Glioblastoma.

MLH1 Promoter Methylation Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic MLH1 promoter methylation analysis (81288) in solid tumors is considered medically necessary when meeting both of the following:
   1. The member/enrollee has a diagnosis of colorectal cancer or endometrial (uterine) cancer,
   2. Previous tumor testing showed loss of MLH1 on immunohistochemistry analysis.

MPL Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic MPL variant analysis (81402, 81403) in or hematologic malignancies is considered medically necessary when:
   1. The member/enrollee displays clinical symptoms of a myeloproliferative neoplasm (i.e., polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myeloid leukemia), such as chronically elevated red blood cell counts.

Microsatellite Instability Analysis (MSI)

1. It is the policy of health plans affiliated with Centene Corporation® that somatic microsatellite instability (MSI) analysis (81301) in solid tumors is considered medically necessary when:
   1. The member/enrollee has a diagnosis of any of the following:
      1. Colorectal cancer,
      2. Endometrial cancer,
      3. Locally advanced or metastatic pancreatic adenocarcinoma,
      4. Gastric cancer,
      5. Locally advanced, recurrent or metastatic esophageal and esophagogastric junction cancer,
      6. Recurrent, progressive or metastatic cervical cancer,
      7. Testicular cancer and has had progression after high dose chemotherapy or third-line therapy,
      8. Unresectable or metastatic Ewing’s sarcoma,
      9. Unresectable or metastatic gallbladder cancer,
      10. Unresectable or metastatic intrahepatic or extrahepatic cholangiocarcinoma,
      11. Unresectable or metastatic breast cancer,
      12. Metastatic and/or recurrent small bowel adenocarcinoma,
      13. Metastatic occult primary.

NPM1 Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic NPM1 variant analysis (81310, 0049U) in hematological malignancies is considered medically necessary when:
   1. The member/enrollee has cytogenetically normal acute myeloid leukemia (AML).

NRAS Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic NRAS variant analysis (81311) in solid tumors is considered medically necessary when:
   1. The member/enrollee has suspected or proven metastatic, synchronous or metachronous colorectal cancer.

PIK3CA Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic PIK3CA variant analysis (81309, 0155U, 0177U) in solid tumors is considered medically necessary when meeting either of the following:
   1. The member/enrollee has recurrent or stage IV, HR positive, HER2 negative invasive breast cancer,
   2. The member/enrollee has a diagnosis of uterine carcinosarcoma or uterine rhabdomyosarcoma.

RET Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic RET variant analysis (81404, 81405, 81406) in solid tumors is considered medically necessary when meeting either of the following:
   1. The member/enrollee has a diagnosis of medullary thyroid cancer,
   2. Anaplastic thyroid carcinoma or locally recurrent, advanced and/or metastatic papillary, follicular or Hurthle cell thyroid carcinoma.

TP53 Variant Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that somatic TP53 variant analysis (81405) in bone marrow or peripheral blood is considered medically necessary when meeting either of the following:
   1. The member/enrollee has a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL),
   2. The member/enrollee is undergoing diagnostic workup for mantle cell lymphoma (MCL).

Measurable (Minimal) Residual Disease (MRD) Analysis

1. It is the policy of health plans affiliated with Centene Corporation® that measurable (minimal) residual disease analysis (0171U, 81479) in bone marrow or peripheral blood is medically necessary when:
   1. The member/enrollee has a diagnosis of any of the following:
      1. Acute Lymphoblastic Leukemia (ALL),
      2. Multiple Myeloma,
      3. Chronic Lymphoblastic Leukemia

Red Blood Cell Genotyping in Multiple Myeloma

1. It is the policy of health plans affiliated with Centene Corporation® that red blood cell genotyping (81479, 0001U, 0180U, 0221U) in individuals with multiple myeloma is considered medically necessary when meeting all of the following:
   1. The member/enrollee has a diagnosis of multiple myeloma,
   2. The member/enrollee is currently being treated with Daratumumab (DARA),
   3. One of the following:
      1. Auto- or allo-antibodies are detected,
      2. RBC phenotyping cannot be performed due to a transfusion within the prior three months.

Whole Exome and Whole Genome Sequencing in Cancer

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support whole exome sequencing and whole genome sequencing in solid tumors (0013U, 0036U, 81415, 81416) and hematologic malignancies (0014U, 0056U, 81425, 81426).

Genetic Testing to Confirm the Identity of Laboratory Specimens

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support genetic testing to confirm the identity of laboratory specimens (e.g., know error, ToxProtect, ToxLok) (0007U, 0079U, 81265, 81266, 81479), when billed separately, because it is generally considered to be an existing component of the genetic testing process for quality assurance.

Codes Used In This BI: