CurrentCapital BluecrossPolicy MP 2.337

Proteomic Testing for Targeted Therapy in Non-Small Cell Lung Cancer

Policy governs coverage determination for proteomic testing (including VeriStrat) when used to predict survival or to select targeted therapy for management of non-small-cell lung cancer (NSCLC) for Capital Blue Cross-administered programs; indicates investigational status and cross-references related molecular testing policies.

Policy Summary

PayerCapital Bluecross

PolicyProteomic Testing for Targeted Therapy in Non-Small Cell Lung Cancer

Policy CodePolicy MP 2.337

Change TypeAdministrative / coding updates (no change to policy statement)

Effective Date12/01/2025

Next Review Date

Key ActionIf coverage of a test is requested but is not listed in this policy, refer to MP 2.259 - Expanded Molecular Panel Testing of Cancers to Identify Targeted Therapies for additional guidance.

POLICY UPDATE CHANGES

09/27/2023 Consensus Review: Coding table and references updated; removed 0080U from policy as it does not apply to cancer management.

10/04/2022 Consensus Review: No change to policy statement. NCCN language added. Cross referenced policies updated. FEP language revised. Background, Rationale and References updated.

04/07/2021 Consensus Review: Description/Background updated. References updated. No change to policy statement.

07/20/2020 Consensus Review: Reference updates. No changes to policy statement.

Removed 0080U from policy as it does not apply to cancer management.

09/23/2024 Consensus Review: Coding table and references updated.

10/04/2022 Consensus Review: FEP language revised; added NCCN language and cross referenced policies updated.

Planned Administrative Update 10/29/2025: Removed Benefit Variations Section and updated Disclaimer.

1Primary coverage stance (investigational/not covered)

Coverage Summary

This policy governs coverage determinations for proteomic testing (including the VeriStrat assay) when used to predict survival or to select targeted therapy for non-small-cell lung cancer (NSCLC) in programs administered by Capital Blue Cross. The use of proteomic testing, including but not limited to VeriStrat, is considered investigational / not covered for all uses in the management of NSCLC.

Policy metadata

Policy NumberMP 2.337

Effective Date12/1/2025

Last Review09/27/2023

SubjectProteomic testing (e.g., VeriStrat) for targeted therapy in non-small-cell lung cancer

Scope SummaryPolicy governs coverage determination for proteomic testing (including VeriStrat) to predict survival or select targeted therapy for NSCLC for Capital Blue Cross–administered programs; proteomic testing is considered investigational and not covered for management of NSCLC, with related cross-references to molecular testing policies.

Medical Necessity / Investigational Determinations

Medically Necessary / Investigational Determination

Policy statement:

ALL of the following

The use of proteomic testing, including but not limited to the VeriStrat assay, is considered investigational for all uses in the management of non-small-cell lung cancer.
There is insufficient evidence to support a general conclusion concerning the health outcomes or benefits associated with this procedure.

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Coding

Investigational / therefore not covered when used for Proteomic testingCPTNot Covered

81538

Proteomic analysis: multiple reaction monitoring (note: listed as investigational for proteomic testing in NSCLC per policy)

Removed / Not applicable code in cancer managementCPT|HCPCSNot Covered

0080U

Proprietary code removed from policy as it does not apply to cancer management

Coding table updated (no specific codes listed in this part)mixed

No codes listed

Provider Actions & Billing Guidance

Documentation Required

Refer to related molecular testing policy

If coverage of a test is requested but is not listed in this policy, refer to MP 2.259 - Expanded Molecular Panel Testing of Cancers to Identify Targeted Therapies for additional guidance.

Billing Rule

Investigational tests not covered

Proteomic testing for NSCLC (e.g., VeriStrat) is considered investigational and therefore not covered; CPT code 81538 is listed as investigational and not covered when used for proteomic testing in NSCLC.

81538

Background and Evidence Summary

Proteomic tests measure serum or tumor protein patterns (the proteome) using mass spectrometry or protein microarrays and have been proposed as prognostic or predictive markers for response to therapies such as EGFR tyrosine kinase inhibitors in NSCLC. The literature includes retrospective validations, prospective nonrandomized cohort studies, and randomized trials assessing associations between proteomic classifications (for example, VeriStrat 'good' versus 'poor') and outcomes such as overall survival or progression-free survival. Although some studies show prognostic associations, trials have not demonstrated that directing therapy based on proteomic classification improves net health outcomes. Therefore, the evidence is insufficient to demonstrate a net health benefit, and proteomic testing for NSCLC is considered investigational and not covered.

Study / Evidence	Key Finding
Key RCT (PROSE)	VeriStrat classification significantly associated with overall survival in multivariate model (HR good vs poor 1.88; 95% CI 1.25-2.84; p=0.003) but did not establish treatment selection benefit.
EMPHASIS RCT	No significant differences in PFS or OS among VeriStrat groups receiving erlotinib or chemotherapy; results restricted to squamous histology.
Key guideline references cited	ASCO Living Guideline 2023; ACCP Chest 2013; J Clin Oncol 2018 and other proteomic and biomarker studies (multiple PMIDs listed).

Proteomic testing: Measurement and analysis of protein patterns (the proteome) using mass spectrometry or protein microarray to develop prognostic or predictive signatures.

VeriStrat: A commercially available serum-based proteomic test (Biodesix) using MALDI mass spectrometry and an 8-peak signature that classifies samples as 'good' or 'poor' and has been investigated as a prognostic or predictive marker in NSCLC.

Revision History

07/20/2020revised