CONCERT GENETICS ONCOLOGY: CIRCULATING TUMOR DNA AND CIRCULATING TUMOR CELLS (LIQUID BIOPSY)

See Important Reminder at the end of this policy for important regulatory and legal information.

OVERVIEW

Cell-free circulating tumor DNA (ctDNA) originates directly from the tumor tissue (primary or metastasis); as tumor cells die the contents are released into the bloodstream. Genetic tests performed on cell-free circulating tumor DNA (ctDNA), also referred to as a liquid biopsy, potentially offer a noninvasive alternative to tissue biopsy for detection of “driver mutations” or acquired genetic mutations that may guide targeted therapy, and may also be used to track progression of disease.

Circulating tumor cells (CTCs) are intact tumor cells that are shed from tumor cells into the bloodstream or lymphatic system. Most assays detect CTCs through the use of surface epithelial markers such as EpCAM and cytokeratins. The primary reason for detecting CTCs is prognostic rather than for guiding therapeutic choices, through quantification of circulating levels.

POLICY REFERENCE TABLE

Coding Implications

This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2022, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. The inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Please see the Concert Genetics Platform for a comprehensive list of registered tests.

OTHER RELATED POLICIES

This policy document provides criteria for circulating tumor DNA (ctDNA) and circulating tumor cells testing (liquid biopsy). For other oncology-related testing, please refer to:

• Oncology: Molecular Analysis of Solid Tumors and Hematologic Malignancies for criteria related to DNA testing of a solid tumor or a blood cancer.

• Genetic Testing: Hereditary Cancer Susceptibility Syndromes for criteria related to genetic testing to determine if an individual has an inherited cancer susceptibility syndrome.

• Oncology: Algorithmic Testing for criteria related to gene expression profiling and tumor biomarker tests with algorithmic analyses.
• Oncology: Cancer Screening for criteria related to the use of non-invasive fecal, urine, or blood tests for screening for cancer.
• Genetic Testing: General Approach to Genetic and Molecular Testing for criteria related to circulating tumor DNA or circulating tumor cell testing that is not specifically discussed in this or another non-general policy.

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CRITERIA

It is the policy of health plans affiliated with Centene Corporation® that the specific genetic testing noted below is medically necessary when meeting the related criteria:

MOLECULAR PROFILING PANEL TESTS VIA CIRCULATING TUMOR DNA (ctDNA)

Broad Molecular Profiling Panel Tests via Circulating Tumor DNA (ctDNA)

I. Broad molecular profiling panel tests via [circulating tumor DNA (liquid biopsy)](0239U, 0242U, 0326U, 81445, 81455, 81462, 81463, 81464) are considered medically necessary when:

A. The member/enrollee has a diagnosis, progression, or recurrence of one of the following:

1. Advanced (stage IIIb or higher) or metastatic lung adenocarcinoma, OR
2. Advanced (stage IIIb or higher) or metastatic large cell lung carcinoma, OR

3. Advanced (stage IIIb or higher) or metastatic squamous cell lung carcinoma, OR

4. Advanced (stage IIIb or higher) or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS), OR
5. Locally advanced/metastatic pancreatic adenocarcinoma, OR
6. Gastric cancer, OR
7. Esophageal or esophagogastric junction cancer, OR
8. Metastatic prostate cancer, OR
9. Advanced (stage III or higher) cutaneous melanoma, OR
10. Metastatic colorectal cancer, OR
11. Hormone receptor positive/HER2-negative recurrent unresectable or stage IV breast cancer, AND

B. At least one of the following:

1. The member/enrollee 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.

II. Broad molecular profiling panel tests via [circulating tumor DNA (liquid biopsy)](0239U, 0242U, 0326U, 81445, 81455, 81462, 81463, 81464) are considered investigational for all other indications.

III. Broad molecular profiling panel tests via [circulating tumor DNA (liquid biopsy)](0239U, 0242U, 0326U, 81445, 81455, 81462, 81463, 81464) performed simultaneously with solid tumor tissue testing are considered investigational.

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Lung Cancer Focused Panel Tests via Circulating Tumor DNA (ctDNA)

I. Lung cancer focused panel tests via [circulating tumor DNA (ctDNA)](0179U, 81210, 81235, 81275, 81479, 81445) are considered medically necessary when:

A. The member/enrollee has a diagnosis or progression of any of the following:

1. Advanced (stage IIIb or higher) or metastatic lung adenocarcinoma, OR
2. Advanced (stage IIIb or higher) or metastatic large cell lung carcinoma, OR
3. Advanced (stage IIIb or higher) or metastatic squamous cell lung carcinoma, OR
4. Advanced (stage IIIb or higher) or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS), AND

B. At least one of the following:

1. The member/enrollee 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.

II. Lung cancer focused panel tests via [circulating tumor DNA (ctDNA)](0179U, 81210, 81235, 81275, 81479, 81445) are considered investigational for all other indications.

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Colorectal Cancer Focused Panel Tests via Circulating Tumor DNA (ctDNA)

I. Colorectal cancer focused panel tests via [circulating tumor DNA (ctDNA)](81210, 81275, 81311, 81403, 81479) are considered medically necessary when:

A. The member/enrollee has a diagnosis of metastatic colorectal adenocarcinoma, AND

B. Panel includes KRAS, NRAS, and BRAF analysis, AND

C. At least one of the following:

1. The member/enrollee 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.

II. Colorectal cancer focused panel tests via [circulating tumor DNA (ctDNA)](81210, 81275, 81311, 81403, 81479) are considered investigational for all other indications.

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Melanoma Focused Panel Tests via Circulating Tumor DNA (ctDNA)

I. Melanoma focused panel tests via [circulating tumor DNA (ctDNA)](81210, 81311, 81479) are considered medically necessary when:

A. The member/enrollee has a diagnosis or recurrence of advanced (stage III or higher) cutaneous melanoma, AND

B. Panel includes BRAF and NRAS, AND

C. At least one of the following:

1. The member/enrollee 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.

II. Melanoma focused panel tests via [circulating tumor DNA (ctDNA)](81210, 81311, 81479) are considered investigational for all other indications.

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SINGLE GENE MOLECULAR PROFILING PANEL TESTS VIA CIRCULATING TUMOR DNA (ctDNA)

EGFR Variant Analysis via ctDNA

I. EGFR variant analysis (81235) via cell-free circulating tumor DNA (ctDNA) is considered medically necessary when:

A. The member/enrollee has a diagnosis of any of the following:

1. Advanced (stage IIIb or higher) or metastatic lung adenocarcinoma, OR
2. Advanced (stage IIIb or higher) or metastatic large cell lung carcinoma, OR
3. Advanced (stage IIIb or higher) or metastatic squamous cell lung carcinoma, OR
4. Advanced (stage IIIb or higher) or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS), AND

B. The testing is being done at time of diagnosis, OR

C. The testing is being done at the time of progression, AND

D. Treatment with an EGFR tyrosine kinase inhibitor therapy (examples: erlotinib [Tarceva], gefitinib [Iressa], afatinib [Gilotrif], or osimertinib [Tagrisso]) is being considered, AND

E. At least one of the following:

1. The member/enrollee 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.

II. EGFR variant analysis (81235) via cell-free circulating tumor DNA (ctDNA), as a stand alone test, is considered investigational for all other indications.

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BRAF Variant Analysis via ctDNA

I. BRAF variant analysis (81210) via circulating tumor DNA (ctDNA) is considered medically necessary when:

A. The member/enrollee meets one of the following:

1. The member/enrollee has metastatic colorectal cancer, AND a) Testing for NRAS and KRAS is also being performed, either as separate tests or as part of a panel, OR
2. The member/enrollee has stage III or higher cutaneous melanoma, AND a) Is being considered for adjuvant or other systemic therapy, OR
3. The member/enrollee has locally advanced or metastatic pancreatic adenocarcinoma, AND a) Is being considered for anticancer therapy, AND

B. The member/enrollee meets one of the following:

1. The member/enrollee 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.

II. BRAF variant analysis (81210) via circulating tumor DNA (ctDNA) for advanced or metastatic non-small cell lung cancer, when not part of a larger molecular profiling panel, is considered investigational.

III. BRAF variant analysis (81210) via circulating tumor DNA (ctDNA) is considered investigational for all other indications.

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KRAS Variant Analysis via ctDNA

I. KRAS variant analysis (81275, 81276) via circulating tumor DNA (ctDNA) is considered medically necessary when:

A. The member/enrollee has metastatic colorectal cancer, AND

B. Testing for NRAS and BRAF is also being performed, either as separate tests or as part of an NGS panel, OR

C. The member/enrollee has locally advanced or metastatic pancreatic adenocarcinoma, AND

1. Is being considered for anticancer therapy, AND

D. The member/enrollee meets least one of the following:

1. The member/enrollee 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.

II. KRAS variant analysis (81275, 81276) via circulating tumor DNA (ctDNA) for advanced or metastatic non-small cell lung cancer when not part of a larger molecular profiling panel is considered investigational.

  

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