CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Circulating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy)

This policy governs coverage determinations for use of circulating tumor DNA and circulating tumor cells (liquid biopsy) in cancer management for Blue Cross Blue Shield - Rhode Island members, distinguishing Medicare Advantage and Commercial Products.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyCirculating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 12, 2016

Next Review DateN/A

Key ActionVerify member benefits with the provider call center prior to ordering testing, since coverage varies by contract.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredMedicare Advantage

Not medically necessaryCommercial Products

2 CPT codesNon-covered codes

12/01/2016Effective date

03/03/2021

Coverage Determination

General coverage determination

Covered when ALL of the following are met:

Overall coverage stance: The use of circulating tumor DNA (ctDNA) and/or circulating tumor cells (CTCs) is considered not covered or not medically necessary for all indications due to insufficient evidence of clinical validity and clinical utility.

Medicare Advantage: not covered; Commercial products: not medically necessary.

The policy excludes the use of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) for all indications. All indications for ctDNA and CTC testing are not covered / not medically necessary as described in the Medicare Advantage and Commercial sections because the available evidence is insufficient to determine effects on health outcomes.

For Commercial Products, ctDNA and/or CTC testing is considered not medically necessary for all indications. The rationale is that clinical validity and clinical utility have not been established across intended uses (selecting targeted therapy, monitoring treatment response, predicting relapse, and screening); published data demonstrating effects on health outcomes are lacking and available studies are insufficient to support replacing tissue-based analyses.

Coding and Reimbursement

Not covered / Not medically necessary codesCPTNot Covered

86152	Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood)
86153	Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); physician interpretation and report, when required

Provider Actions and Billing Guidance

Note

Prior Authorization

Prior authorization: Not applicable for this policy.

Prior Authorization

Verify Member Benefits and Eligibility

Benefit verification required — benefits and eligibility vary by contract. Providers must verify member-specific coverage in the member's Evidence of Coverage, Benefit Booklet, subscriber agreement, or employer agreement; those documents supersede this policy.

Check the member's Evidence of Coverage/Benefit Booklet or subscriber agreement for coverage details.
For member-specific benefits and eligibility, call the provider call center.

Background

Liquid biopsy refers to analysis of tumor-derived material in peripheral blood, most commonly circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs). ctDNA consists of small fragments of tumor-derived cell-free DNA that are typically present at a low fraction of total cell-free DNA and therefore require highly sensitive detection methods. CTCs are intact tumor cells shed into the bloodstream from primary or metastatic sites; they are typically short-lived and are detected using epithelial surface markers (for example, EpCAM and cytokeratins). Both approaches aim to noninvasively characterize tumors and their genomes but have methodological heterogeneity and limited demonstrated clinical utility.

Definitions

ctDNA — definition and key properties

TermCirculating tumor DNA (ctDNA)

DefinitionCell-free DNA fragments in blood derived from tumor cells (primary tumor, metastases, or CTCs).

Key propertyOften represents a small fraction of total cell-free DNA (usually <1%), requiring highly sensitive detection methods such as digital PCR or BEAMing.

Clinical use describedUsed for genomic characterization of the tumor and to detect known driver mutations (targeted) or by untargeted sequencing approaches.

CTCs — definition and key properties

TermCirculating tumor cells (CTCs)

Line of Therapy / Indication Details

Line-of-therapy related determinations

Use of ctDNA or CTC testing for line-of-therapy decisions is considered not supported when ANY of the following describe the intended clinical use:

Uses evaluated: Testing to select targeted treatment, to monitor treatment response, or to predict relapse (post‑curative) were evaluated, but the evidence is inadequate to establish clinical validity or clinical utility for these purposes.

Randomized trial of CTC‑guided therapy switch showed no overall survival benefit; observational data are insufficient and methods vary across tests.

Biomarker Examples and Requirements

EGFR, ALK (examples) — biomarker examples referenced

ExamplesEGFR and ALK (non–small-cell lung cancer) cited as examples of known driver mutations detectable by targeted ctDNA approaches.

Detection approachesTargeted analysis of known mutations or untargeted methods (eg, next-generation sequencing, whole-exome/genome sequencing).

Clinical validity noteClinical validity must be established independently for each commercially available ctDNA test; published clinical outcome data are lacking.

HER2 — biomarker example

MarkerHER2

ContextHER2 expression has been evaluated on circulating tumor cells in breast cancer; studies and meta-analyses report prognostic and predictive associations.

References and Revision History

2018-06-01reference_list_updateLatest

Reference list includes at least 26 citations related to circulating tumor cells and ctDNA (references numbered through 26).

Policy effective date: 12/01/2016. Policy last updated: 03/03/2021. Status: CURRENT.

Note

Policy notice — verify benefits and do not bill members for non‑covered services without written consent

This medical policy is informational only and does not guarantee payment. Benefits and eligibility are determined by the member's subscriber agreement or employer agreement, which supersede this policy. Contact the provider call center for member-specific benefits and follow contractual terms before billing members.

Policy is not a guarantee of payment and may be revised at any time.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyCirculating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 12, 2016

Next Review DateN/A

Key ActionVerify member benefits with the provider call center prior to ordering testing, since coverage varies by contract.

SourceLink

On This Page

Denial Risk

Denial Risk and Member Financial Responsibility

Denial risk — Medicare Advantage and Commercial plans: circulating tumor DNA and circulating tumor cells (liquid biopsy) are not covered or considered not medically necessary for all indications; claims may be denied and services may be non-covered.

If a service is determined to be not medically necessary or a non-covered benefit, the claim may be denied.
Providers may not bill the member for services determined to be not medically necessary or non-covered unless the member was informed and agreed in writing in advance.

Note

Provider Action: Contact Provider Call Center

Provider action required — contact the provider call center for member-specific questions and before delivering services when coverage is uncertain.

Verify coverage prior to testing to avoid claim denials and unexpected member liability.
Obtain documented member consent in writing if a non-covered service will be provided at the member's expense.

DefinitionIntact tumor cells released into the bloodstream from a primary tumor and/or metastatic sites.

Key propertiesShort circulating half-life (approximately 1–2 hours) and typically detected via epithelial surface markers such as EpCAM and cytokeratins.

Primary rationale for testingPrognostic assessment by quantifying circulating levels; assays include enrichment followed by immunologic, molecular, or functional detection methods.

Circulating tumor cells (CTCs) — research context

Research contextCTCs have been studied as prognostic and predictive biomarkers across multiple tumor types, but clinical validity and utility data are insufficient to support routine clinical use for treatment selection or monitoring.

Detection methodsCTC assays typically include an enrichment step based on biological (marker expression) or physical properties followed by detection; methods vary widely and require independent validation for each commercially available test.

Evidence summaryObservational studies and meta-analyses report prognostic associations (see references for breast, colorectal, prostate, hepatocellular and other cancers), but randomized data showing improved health outcomes are lacking.

ReferencesMultiple studies cited (eg, Fehm et al.; Riethdorf et al.; meta-analyses summarized in references).

PD-L1 — biomarker example

MarkerPD-L1

ContextPD-L1 expression has been reported on circulating tumor cells in breast cancer; frequency and potential predictive value are described in referenced studies.

Reference exampleMazel et al. report frequent PD-L1 expression on circulating breast cancer cells (see references).

Estrogen receptor (ER) — biomarker example

MarkerEstrogen receptor (ER)

ContextHeterogeneity of ER expression in circulating tumor cells from metastatic breast cancer has been documented; this has research implications for prognostication and therapy selection but lacks demonstrated clinical utility.

ReferenceBabayan et al. and other referenced studies examine ER heterogeneity in CTCs in metastatic breast cancer.

Do not charge members for non‑covered services unless they agreed in writing in advance.

Prior authorization is listed as not applicable for this policy, but benefit verification is required.