CurrentCapital BluecrossPolicy MP 2.315

Gene expression profile testing and circulating tumor DNA testing for predicting recurrence in colon cancer

This policy governs coverage determinations for gene expression profile (GEP) assays and circulating tumor DNA (ctDNA) assays used to predict recurrence in stage II or stage III colon cancer following surgery for members of Capital Blue Cross programs.

Policy Summary

PayerCapital Bluecross

PolicyGene expression profile testing and circulating tumor DNA testing for predicting recurrence in colon cancer

Policy CodePolicy MP 2.315

Change TypeNo material change

Effective DateDec 1, 2025

Next Review DateN/A

Key ActionDo not expect investigational GEP or ctDNA tests (including codes 81525 and 0229U) to be covered; prior authorization will not make investigational services covered.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

stage II/IIIdisease stages

investigationalGEP stance

investigationalctDNA stance

CLIACLIA

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

Investigational — GEP and ctDNA for prognostication in stage II/III colon cancer

Covered when ALL of the following are met

Primary coverage stance: Gene expression assays and circulating tumor DNA assays for determining prognosis of stage II or stage III colon cancer following surgery are considered investigational due to insufficient evidence that use improves net health outcomes.

Available evidence shows improved risk prediction for GEP and an association between positive ctDNA and recurrence, but studies are limited (observational designs, small numbers) and do not demonstrate that test-guided management improves disease-specific survival or other net health outcomes; one randomized trial of ctDNA-guided management showed similar progression-free survival between groups.

Use of gene expression profile (GEP) assays and circulating tumor DNA (ctDNA) assays to determine prognosis in patients with stage II or stage III colon cancer following surgical resection is considered investigational. There is insufficient evidence that use of these tests improves net health outcomes, and available studies do not establish that test-guided management improves clinically meaningful outcomes.

The procedure codes 81525 and 0229U are identified in this policy as investigational and are therefore not covered.

Gene expression assays and circulating tumor DNA assays intended to predict recurrence risk after surgery for stage II or III colon cancer are categorized as investigational because current evidence, including cohort and decision-impact studies, is insufficient to demonstrate improved patient outcomes when these tests are used to guide management.

Procedure codes designated as investigational in this policy (including 81525 and 0229U) are reiterated here as not covered when billed.

Covered Indications

None specified — GEP and ctDNA prognostic testing for stage II or III colon cancer are considered investigational and therefore not covered.

Not covered — investigational tests and codes: Gene expression profile (GEP) assays and circulating tumor DNA (ctDNA) assays for predicting recurrence in stage II or III colon cancer following surgery are considered investigational and are not covered.

Procedure codes identified as investigational (81525, 0229U) are not covered; prior authorization will not make investigational services covered. Coverage determinations remain subject to member benefit terms and eligibility on the date of service.

Not Covered

Gene expression profile assays and circulating tumor DNA assays for predicting recurrence in stage II or stage III colon cancer following surgery are considered investigational and not covered due to insufficient evidence that testing improves clinical outcomes.

Tests billed using procedure codes 81525 and 0229U are classified as investigational under this policy and are therefore not covered.

Coding

Covered CPT Codesmixed

not listed

No specific CPT/HCPCS/ICD-10 codes are listed in this document portion.

Investigational; therefore, not coveredCPTNot Covered

81525	Procedure Code listed as Investigational; therefore, not covered
0229U	Procedure Code listed as Investigational; therefore, not covered

Provider Actions and Billing Notes

Denial Risk

Investigational codes — denial risk

Tests and procedure codes listed as investigational are not covered and may be denied when billed. Prior authorization will not make investigational services eligible for coverage. Providers should verify member benefits and eligibility on the date of service before ordering or billing these tests.

Investigational procedure codes: 81525, 0229U — not covered; claims may be denied.
Prior authorization does not override investigational designation and will not make services eligible for coverage.
Determine member eligibility and benefit limitations on date of service; medical necessity documentation must support any coverage determination.

Note

Laboratory and product variation note

Laboratory-developed tests (LDTs) must be performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories for high-complexity testing. The U.S. Food and Drug Administration has not required regulatory review for these tests. Program- and product-specific benefit variations apply; this policy is only applicable to certain Capital Blue Cross programs and products (see Product Variations).

Background

Multigene gene expression profile (GEP) assays and circulating tumor DNA (ctDNA) tests have been developed as prognostic markers to identify patients with stage II or III colon cancer at higher risk for recurrence after surgery who might be candidates for adjuvant chemotherapy. Standard clinicopathologic features (for example, T4 tumors, obstruction/perforation, fewer than 12 lymph nodes sampled, aggressive histology, or positive margins) continue to guide adjuvant therapy decisions, and tumor characteristics such as microsatellite instability/mismatch repair deficiency may confound interpretation of prognostic test results. Laboratory-developed tests must be performed in CLIA-certified high-complexity laboratories.

Definitions

ADENOMA

TermADENOMA

DefinitionA benign tumor made of epithelial cells, usually arranged like a gland.

ContextListed among definitions relevant to colon pathology in the policy.

LYNCH SYNDROME

TermLYNCH SYNDROME

DefinitionA hereditary predisposition to nonpolyposis colorectal cancer and other solid tumors.

ContextIncluded in policy definitions relevant to inherited colon cancer syndromes.