CurrentCapital BluecrossPolicy MP 2.375

Molecular testing in the management of pulmonary nodules

This medical policy governs coverage determinations for plasma-based proteomic screening tests (e.g., Nodify XL2, Nodify CDT, REVEAL) and gene expression profiling of bronchial brushings (Percepta GSC) when used in the diagnostic management of undiagnosed pulmonary nodules detected by CT or following indeterminate bronchoscopy results for suspected lung cancer. It applies to products administered by Capital Blue Cross with noted product/program variations.

Policy Summary

PayerCapital Bluecross

PolicyMolecular testing in the management of pulmonary nodules

Policy CodePolicy MP 2.375

Change TypeConsensus & Administrative updates

Effective DateNov 1, 2025

Next Review Date

Key ActionVerify member-specific benefits and product variations and determine coverage by member benefit terms and medical necessity.

POLICY UPDATE CHANGES

07/09/2025 Consensus Review. No change to policy statement. Updated coding table; relocated codes 0080U, 0092U, 0360U to MP 2.277 & Removed 84999 from the policy.

10/07/2025 Administrative Update. Removed Benefit Variations Section and updated Disclaimer.

01/24/2025 Administrative Update. Removed NCCN statement.

2Test classes designated investigational

1Procedure codes listed as investigational

2025-11-01Policy effective date

Coverage Summary

Scope: This policy governs coverage determinations for plasma-based proteomic screening tests (for example, Nodify XL2, Nodify CDT, REVEAL) and gene expression profiling of bronchial brushings (for example, Percepta GSC) when used in the diagnostic management of undiagnosed pulmonary nodules detected by computed tomography or following indeterminate bronchoscopy results. Coverage applicability is to products administered by Capital Blue Cross with noted product/program variations.

Coverage stance: mixed — the policy designates the test classes at issue as investigational (see policy determinations) and lists investigational procedure codes; it is current and effective 11/01/2025 with last review on 07/09/2025.

Policy metadata

Policy NumberMP 2.375

Policy StatusCURRENT

Effective Date11/1/2025

Last Review07/09/2025

Scope SummaryCoverage determinations for plasma-based proteomic screening tests (e.g., Nodify XL2, Nodify CDT, REVEAL) and gene expression profiling of bronchial brushings (Percepta GSC) when used in the diagnostic management of undiagnosed pulmonary nodules detected by CT or following indeterminate bronchoscopy results; applies to products administered by Capital Blue Cross with product/program variations.

Medical‑Necessity & Coverage Determinations

Proteomic Plasma-based Screening - Coverage Determination

Plasma-based proteomic screening in individuals with undiagnosed pulmonary nodules detected by computed tomography is:

ALL of the following

Test type: Plasma-based proteomic screening (including but not limited to Nodify XL2® (BDX-XL2), Nodify CDT®, and REVEAL Lung Nodule Characterization (MagArray))
listed examples are not exhaustive
Indication: Individuals with undiagnosed pulmonary nodules detected by computed tomography
any nodule detected by CT
Policy determination: Considered investigational due to insufficient evidence to support a general conclusion concerning health outcomes or benefits
Therefore not supported as medically necessary by this policy

Gene Expression Profiling of Bronchial Brushings - Coverage Determination

Gene expression profiling on bronchial brushings in individuals with undiagnosed pulmonary nodules following indeterminate bronchoscopy is:

ALL of the following

Test type: Gene expression profiling on bronchial brushings (including but not limited to Percepta® Genomic Sequencing Classifier)
including first- and second-generation Percepta tests
Indication: Individuals with indeterminate bronchoscopy results from undiagnosed pulmonary nodules
intended to assist subsequent management (rule-in or rule-out) but does not diagnose lung cancer
Policy determination: Considered investigational due to insufficient evidence to support a general conclusion concerning health outcomes or benefits
Thus not supported as medically necessary by this policy

Not Medically Necessary / Investigational

Determination: Both plasma-based proteomic screening and gene expression profiling of bronchial brushings are considered investigational due to insufficient evidence to support a general conclusion that use of these tests improves net health outcomes.

Regulatory context: These tests are offered as laboratory-developed tests under CLIA (laboratories must be CLIA high-complexity licensed), and the FDA has not required regulatory review of these specific tests.

Investigational metrics

Test classes designated investigational2

Procedure codes listed as investigational1

Provider Actions & Billing Guidance

Documentation Required

Applicability and benefit variation

Providers must verify member-specific benefits and product variations before ordering or billing for molecular testing for pulmonary nodules. This policy applies only to certain programs and products administered by Capital Blue Cross and is subject to benefit variations; for example, FEP PPO follows the FEP Medical Policy Manual.

Example: FEP PPO — refer to FEP Medical Policy Manual

Billing Rule

Coding list does not guarantee coverage

Identification of a code in the coding section does not denote coverage. Coverage and payment are determined by the member's benefit program terms, eligibility on the date of service, and a determination that the services are medically necessary and appropriate.

Affected code: 81479

Background & Evidence Summary

Rationale: Plasma-based proteomic screening measures protein concentrations or signatures (examples include Nodify XL2, Nodify CDT, REVEAL) intended to risk-stratify pulmonary nodules to reduce unnecessary invasive procedures; bronchial brush gene expression profiling (Percepta GSC and earlier Percepta versions) measures airway gene activity to assist post-bronchoscopy management decisions but does not diagnose lung cancer.

Regulatory and evidence considerations: These assays are commercially available as laboratory-developed tests under CLIA and have not undergone FDA review. Although clinical validation studies exist (including validation cohorts for Nodify XL2 and REVEAL and multicenter prospective validation for Percepta GSC), limitations such as evolving test versions, exclusions from validation cohorts, small sample sizes, dependence on specific clinical models, and need for independent validation mean the evidence is insufficient to demonstrate an improvement in net health outcomes.

Study / Finding	Key Result / Limitations
Nodify XL2 specificity (validation study)	Validation study showed 97% specificity in low-to-moderate pretest probability (≤50%) patients; primary limitation: many patients excluded for incomplete clinical data or determined outside intended-use population; uncertainty whether intended-use population was determined a priori; need validation in independent intended-use sample.
REVEAL validation	Retrospective study demonstrated rule-out use with VA Clinical Factors Model; correctly identified 65% of intermediate-risk samples; NPV and sensitivity 94%; limitations: small sample size and use with a single testing model; needs validation in independent samples and additional probability models.
Percepta GSC validation	Three-cohort prospective multicenter validation showed down-classification of intermediate-risk to low with 91% NPV and up-classification to high with 65% PPV; further assessment of clinical utility and where test fits in clinical pathway is needed.

Definitions

ProteomicsStudy of the structure and function of proteins; used to measure protein concentrations/characteristics to identify disease.

Gene Expression Profiling (GEP)Measurement of gene activity (mRNA) within cells to assess risk for malignancy.

Revision History

10/07/2025Administrative UpdateLatest

Removed Benefit Variations Section and updated Disclaimer.

07/09/2025Consensus Review

No change to policy statement. Updated coding table; relocated codes 0080U, 0092U, 0360U to MP 2.277 and removed 84999 from the policy.

01/24/2025Administrative Update

Removed NCCN statement.