CurrentCapital BluecrossPolicy MP 2.343

Proteogenomic testing for patients with cancer

This policy governs coverage of proteogenomic testing (integration of proteomic, transcriptomic, and genomic data) for individuals with cancer for Capital BlueCross products to which the policy applies.

Policy Summary

PayerCapital Bluecross

PolicyProteogenomic testing for patients with cancer

Policy CodePolicy MP 2.343

Change TypeRoutine review — no material changes

Effective DateJan 1, 2025

Next Review DateN/A

Key ActionVerify member benefit coverage and prior authorization requirements with the member's specific product before ordering testing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

investigationalcoverage stance

GPS Cancerexample test

1/1/2025effective

1procedure codes

Coverage Criteria — Proteogenomic Testing

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Investigational (Not covered)

Investigational (Not covered): Proteogenomic testing of individuals with cancer (including but not limited to the GPS Cancer test) is considered investigational for all indications due to insufficient evidence to support a general conclusion about improved health outcomes or clinical benefit.

Effective 1/1/2025

Not covered — investigational

Coverage determination

Investigational stance: Proteogenomic testing of patients with cancer (including but not limited to the GPS Cancer test) is considered investigational for all indications and is therefore not covered.

Evidence is insufficient to demonstrate clinical validity or clinical utility; testing methods are not standardized or validated.

Proteomic testing that measures protein products alone (without integration of genomic and transcriptomic information) is explicitly distinguished from proteogenomic testing in this policy. When only protein-level measurements are performed, those assays are not considered proteogenomic testing under this policy and therefore are not evaluated by the proteogenomic coverage statements in this document.

Proteogenomic testing — including commercially available tests such as the GPS Cancer test — is considered investigational and not covered for all indications. The rationale is that available studies are early-stage (cross‑sectional and cohort studies) and there is no published evidence demonstrating clinical validity or clinical utility

The provided document excerpts do not list any additional explicit exclusions beyond the distinction between proteomic (protein-only) testing and proteogenomic testing; no other test-specific or indication-specific exclusions are stated in the supplied chunks.

Because proteogenomic testing (for example, GPS Cancer) is considered investigational for all indications in this policy, it is therefore regarded as not medically necessary for any clinical indication covered by this policy due to insufficient evidence that such testing provides health benefit.

The evidence summary notes there is no published evidence on the clinical validity or utility of the GPS Cancer test and that proteogenomic research is at an early stage. Very few studies have applied proteogenomic markers for diagnosis or prognosis, and further work is required to standardize and validate analytic methods before clinical utility can be established.

The text excerpts provided do not contain the literal phrase "not medically necessary" in the quoted sections; however, the policy's investigational / not covered stance implies that proteogenomic tests may be denied as not medically necessary based on the stated insufficiency of evidence and investigational determination.

Covered Indications and Test-Specific Notes

GPS Cancer test intended use vs evidence

Intended use vs evidence: The GPS Cancer test is a commercially available proteogenomic assay intended to inform personalized treatment decisions by integrating whole‑genome sequencing, whole‑transcriptome sequencing, and quantitative proteomics; however, there is no published evidence demonstrating the clinical validity or clinical utility of the GPS Cancer test to support its use for routine clinical decision making.

Further research and standardization of proteogenomic testing methods are needed before clinical benefit can be established.

Proteogenomic evaluation in research or characterization contexts

Research/characterization context: Proteogenomic evaluations and related analyses are described in research and tumor‑characterization studies and referenced proteome databases and analytic pipelines (for example CPTAC pipelines and multiple proteome databases), but these citations reflect research contexts and do not define covered clinical indications.

References include multiple literature citations and database resources; no evidence establishes improved patient outcomes for clinical use.

Not Covered — Investigational

Proteogenomic testing for individuals with cancer — including but not limited to the GPS Cancer test — is considered investigational for all indications and therefore not covered under this policy.

Proteogenomic testing of patients with cancer (including, but not limited to, the GPS Cancer test) is explicitly stated as investigational and not covered for any indication in the coding/coverage information section of the policy.

In the supplied excerpts there are no enumerated lists of specific tests or clinical indications set out as individually not covered beyond the general investigational determination; the document instead applies the investigational / not covered conclusion to proteogenomic testing broadly.

Provider Actions and Billing Guidance

Prior Authorization
Benefit and prior authorization verification
This policy applies only to certain Capital Blue Cross products and program designs. Providers should verify the member's specific benefits and whether prior authorization is required before ordering proteogenomic testing.
Applies only to products administered by Capital Blue Cross; benefit variations may exist.
Providers should consult the member's health benefit plan or contact Capital Blue Cross for benefit and prior authorization information.

Billing Rule
Coding and preauthorization note
The identification of a billing or procedure code in this policy does not imply that the service is a covered benefit. Coverage is determined by the member's benefit plan and some services may require preauthorization.
Procedure code listed for proteogenomic testing: 81479
Presence of a code in this section does not denote coverage; check member benefit language.

Denial Risk
Prior authorization and denial risk
Proteogenomic testing for patients with cancer (including, but not limited to, GPS Cancer) is considered investigational for all indications under this policy. Coverage decisions and any preauthorization requirements are governed by the member's benefit plan; providers should assume a high risk of denial for investigational services unless plan documents state otherwise and should obtain any required prior authorization.
Proteogenomic testing (e.g., GPS Cancer) is considered investigational for all indications and therefore not covered under this policy.
Obtain prior authorization when required by the member's plan; absence of prior authorization may result in claim denial.

Note
Genetic counseling recommended
Recommend formal genetic counseling performed by a clinician experienced in genetic medicine and testing methods when genetic testing for an inherited condition is being considered. Counseling can help patients understand benefits, harms, and familial implications, and may affect testing decisions.
Genetic counseling is recommended for patients at risk for inherited disorders or when genetic testing is considered.
Counseling should be provided by a clinician with expertise in genetic medicine and testing methods.

Documentation Required
Benefit verification and plan documentation
Providers should consult the member's health benefit plan language or contact Capital Blue Cross Provider Services or Member Services to determine coverage, benefit limits, and preauthorization requirements for proteogenomic testing.
Benefit determinations are based on the applicable health benefit plan language; medical policies do not describe member benefits.
Contact Capital Blue Cross Provider Services or Member Services for questions about application to a specific member's plan.

Step Therapy
Step therapy
No step therapy requirements for proteogenomic testing are described in this policy. Treating providers should still verify any plan-specific utilization management rules that may apply.
No step therapy described in the policy excerpts.
Verify plan-specific utilization management (step therapy or other) with the member's benefit plan.

Denial Risk
Claims and denial implication
Proteogenomic testing for patients with cancer is considered investigational for all indications; claims may be denied on that basis. Providers should document clinical rationale when ordering tests and confirm coverage before performing testing.
Investigational designation creates a denial risk for claims related to proteogenomic testing.
Document clinical rationale and obtain preauthorization when required by the member's plan.

Definitions and Background

Proteogenomics integrates genomic, transcriptomic, and proteomic data to better characterize tumor biology. The approach aims to identify diagnostic, prognostic, and predictive biomarkers; quantify protein expression and modifications over time; and relate protein-level findings to genomic drivers. Methods described in the literature and policy background include whole‑genome and whole‑transcriptome sequencing combined with quantitative proteomics (top‑down and bottom‑up mass spectrometry) and bioinformatics pipelines to integrate these data for tumor characterization.

Proteogenomic testing — definition

DefinitionProteogenomic testing: integration of proteomic, transcriptomic, and genomic information to provide a comprehensive view of genome function and protein products, used to detect cancer signatures, identify biomarkers, and correlate protein profiles with disease states.

ScopeApplied to combined analysis of genome, transcriptome (RNA), and proteome data to characterize tumors and inform research or potential clinical hypotheses.

DistinctionDistinct from proteomic-only testing because it requires integration of genomic and transcriptomic information with proteomic data.

Proteomic testing — definition

DefinitionProteomic testing: measurement of protein products alone (the proteome) without integration of genomic or transcriptomic information.

Policy noteWhen protein products alone are tested, this is not considered proteogenomic testing under this policy.

ApplicationsMay include large-scale profiling of proteins but lacks the genomic/transcriptomic context required for proteogenomic interpretation.

Top-down mass spectrometry — definition

DefinitionTop-down mass spectrometry: identification and characterization of intact proteins in a sample without prior knowledge of which proteins are present, providing comprehensive protein profiles including posttranslational modifications and protein isoforms.

CapabilityProvides protein 'profiles' or 'maps' and allows isolation of intact proteins for further sequencing and analysis.

ContextDescribed as a method that documents posttranslational modifications and other isoforms useful for proteogenomic characterization.

Bottom-up mass spectrometry — definition

DefinitionBottom-up mass spectrometry: identification of proteins by analyzing peptide fragments that indicate the presence of specific proteins; relies on peptide fragments to identify proteins.

Technique exampleSelective reaction monitoring is a bottom-up modification that permits direct quantification and specific identification of low‑abundance proteins using target peptide 'signatures'.

Use caseMultiplex assays using bottom-up approaches can quantify multiple receptor proteins (e.g., EGFR, HER2, HER3) in a sample.

Bioinformatics platforms used in proteogenomics

DefinitionBioinformatics platforms in proteogenomics: software tools that integrate genomic and proteomic data to interpret complex proteogenomic results.

ExamplesNamed tools include PARADIGM, the Proteogenomic Mapping Tool, Genome Peptide Finder, Peppy, and VESPA.

RoleThese platforms map peptides to the genome, match predicted peptide sequences, automate searches from translated databases, and provide visual integration of data for analysis.

Proteogenomic testing (integrated analysis) — definition

Integrated analysisProteogenomic testing combines proteomic and genomic (molecular) characterization of tumors to understand protein-level expression, modifications, and their genomic drivers.

ObjectivesAims include detecting cancer signatures, identifying diagnostic/prognostic/predictive biomarkers, quantifying protein levels over time, and correlating protein profiles with disease states.

Research contextDescribed primarily as an investigational and research-focused approach with diverse analytic methods and limited standardization in clinical application.

Revision History and References

2024-11-19Administrative updateLatest

Removed NCCN statement from policy history.

2024-03-21Consensus review

Consensus review with no change to the policy statement; references updated.

2024-01-19Administrative update

Administrative update adding clinical benefit language.

2023-08-07Consensus review

Consensus review with no change to the policy statement; background updated.

2022-08-30Consensus review

Consensus review with no change to the policy statement; NCCN language added and product variation, background, rationale, and references updated.

2021-11-04Consensus review

Consensus review for FEP and references with no changes to coding.

2020-06-22Consensus review

Consensus review with no change to policy statement; coding reviewed and references updated; product variation statement updated.

This policy references external materials and scientific literature to support the rationale, including the Blue Cross Blue Shield Association Medical Policy Reference Manual section 2.04.140 on proteogenomic testing for patients with cancer and multiple peer‑reviewed studies (selected citations span approximately 2010–2021) that describe proteogenomic characterization and related analytic resources.