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.

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.

Molecular Profiling Panel Tests Via Circulating Tumor DNA (CTDNA)

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

1. It is the policy of health plans affiliated with Centene Corporation® that Comprehensive molecular profiling panel tests via circulating tumor DNA (liquid biopsy) (0239U, 0242U, 81455) is considered medically necessary when meeting all of the following:
   1. The member/enrollee has a diagnosis of one 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),
      5. Locally advanced / metastatic pancreatic adenocarcinoma,
      6. Gastric cancer,
      7. Esophageal or Esophagogastric Junction cancer,
      8. Metastatic prostate cancer,
   2. The member/enrollee is a candidate for an anti-cancer therapy,
   3. At least one of the following:
      1. The member/enrollee is medically unfit for invasive tissue sampling (biopsy),
      2. The member/enrollee does not have a biopsy-amenable lesion.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support comprehensive molecular profiling panel tests via circulating tumor DNA (liquid biopsy) (0239U, 0242U, 81455) for all other indications.
3. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support comprehensive molecular profiling panel tests via circulating tumor DNA (liquid biopsy) (0239U, 0242U, 81455) performed simultaneously with, or subsequent to, solid tumor tissue testing.

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

1. It is the policy of health plans affiliated with Centene Corporation® that lung cancer focused panel tests via circulating tumor DNA (ctDNA) (0179U, 81210, 81235, 81276) are 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 a candidate for an anti-cancer therapy,
   3. At least one of the following:
      1. The member/enrollee is medically unfit for invasive tissue sampling (biopsy),
      2. The member/enrollee does not have a biopsy-amenable lesion.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support lung cancer focused panel tests via circulating tumor DNA (ctDNA) for all other indications.

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

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support colorectal cancer focused panel tests via circulating tumor DNA (ctDNA) (81210, 81275, 81276, 81311).

Melanoma Focused Panel Tests via Circulating Tumor DNA (ctDNA)

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support melanoma focused panel tests via circulating tumor DNA (ctDNA) (81210, 81311).

Single Gene Molecular Profiling Panel Tests Via Circulating Tumor Dna (CtDNA)

EGFR Variant Analysis via ctDNA

1. It is the policy of health plans affiliated with Centene Corporation® that EGFR variant analysis (81235) via cell-free circulating tumor DNA (ctDNA) 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 testing is being done at time of diagnosis or at the time of progression,
   3. Treatment with an EGFR tyrosine kinase inhibitor therapy (eg, erlotinib [Tarceva], gefitinib [Iressa], afatinib [Gilotrif], or osimertinib [Tagrisso]) is being considered,
   4. At least one of the following:
      1. The member/enrollee is medically unfit for invasive tissue sampling (biopsy),
      2. The member/enrollee does not have a biopsy-amenable lesion.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support EGFR variant analysis (81235) via cell-free circulating tumor DNA (ctDNA), as a stand alone test, for all other indications.

BRAF Variant Analysis via ctDNA

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support BRAF variant analysis (81210) via circulating tumor DNA (ctDNA), as a stand alone test.

KRAS Variant Analysis via ctDNA

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support KRAS variant analysis (81275, 81276) via circulating tumor DNA (ctDNA), as a stand alone test.

NRAS Variant Analysis via ctDNA

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support NRAS variant analysis (81311) via circulating tumor DNA (ctDNA), as a stand alone test.

PIK3CA Variant Analysis via ctDNA

1. It is the policy of health plans affiliated with Centene Corporation® that PIK3CA variant analysis (0177U, 81309) via circulating tumor DNA (ctDNA) is considered medically necessary when:
   1. The member/enrollee has recurrent or stage IV hormone receptor-positive/  HER2-negative breast cancer.
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support PIK3CA variant analysis (0177U, 81309) via circulating tumor DNA (ctDNA), as a stand alone test, for all other indications.

Circulating Tumor Cell Tests

AR-V7 Androgen Receptor Splice Variant Analysis in Circulating Tumor Cells (CTCs)

1. It is the policy of health plans affiliated with Centene Corporation® that AR-V7 androgen receptor splice variant analysis (81479) in circulating tumor cells (CTCs) is considered medically necessary when meeting both of the following:
   1. The member/enrollee has metastatic castration-resistant prostate cancer (M1 CRPC),
   2. The member/enrollee has had a progression after first-line treatment with enzalutamide (Xtandi®) or abiraterone (Zytiga®).
2. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support AR-V7 androgen receptor splice variant analysis (81479) in circulating tumor cells (CTCs) for all other indications.

Circulating Tumor Cell (CTC) Enumeration

1. It is the policy of health plans affiliated with Centene Corporation® that current evidence does not support circulating tumor cell (CTC) enumeration (86152, 86153).

Notes and Definitions

Cell-free circulating tumor DNA (ctDNA) is fragmented, tumor-derived DNA circulating in the bloodstream that is not being carried in a cell. ctDNA derives either directly from the tumor or from circulating tumor cells.

Circulating Tumor Cells (CTCs) are intact cells that have shed into the bloodstream or lymphatic system from a primary tumor or a metastasis site, and are carried around the body by blood circulation.

Cell-free circulating tumor DNA analysis should not be used in lieu of a histologic tissue diagnosis, however there are specific clinical considerations, outlined above, where the use of ctDNA may be considered.

Cell-free circulating tumor DNA analysis should not be performed simultaneously with tissue testing of a solid tumor.

If cell-free circulating tumor DNA analysis is negative, follow-up with tissue-based analysis is recommended.

Codes Used In This BI: