CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Gene Expression Profile Testing and Circulating Tumor DNA Testing for Predicting Recurrence in Colon Cancer

Defines medical coverage and coding for Oncotype DX Colon and related GEP/ctDNA prognostic tests for stage II and III colon cancer following surgery for BCBSRI Medicare Advantage and commercial products.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyGene Expression Profile Testing and Circulating Tumor DNA Testing for Predicting Recurrence in Colon Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective Date01 01 2024

Next Review DateN/A

Key ActionOrdering physician must be involved in authorization and administrative processes; laboratories may not obtain authorization on behalf of the ordering physician.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

01 01 2024Effective date

Stage II/IIIIntended population

81525CPT referenced

CLIARegulatory standard

C18-C20,C21.1

Coverage Criteria

Medically Necessary Coverage

Covered when ALL of the following are met for Medicare Advantage Plans and Commercial Products:

Population: Patient with stage II or stage III colon cancer following surgical resection being evaluated for recurrence risk to inform adjuvant chemotherapy decisionsstage II or III

See policy overview and policy statement

Test: Oncotype DX Colon (Genomic Health) 12-gene mRNA gene expression profiling assay (CPT 81525)CPT 81525

Assay description per CPT code listing

Laboratory/Regulatory: Test must be performed as a CLIA high-complexity laboratory service (commercial or laboratory-developed test)CLIA high-complexity

LDTs and CLIA requirement referenced in policy definitions

Some employer or group contracts include explicit exclusions for expanded biomarker-related coverage under the state mandate. When such a contract exclusion applies, the expanded biomarker services described in this policy may not be covered for members of that group; determine coverage by reviewing the member's Benefit Booklet.

Medical criteria: Not applicable. This document does not provide a separate medical-criteria table.

Covered Indications

Prognostic testing to predict recurrence risk in stage II or III colon cancer following surgery to inform adjuvant chemotherapy decisions.

Intended use: Use of gene expression profiling and/or circulating tumor DNA assays to estimate recurrence risk after surgical resection for stage II or III colon cancer to inform adjuvant chemotherapy decisions

Supporting evidence

12-gene assay studies: Key validation and impact studies include Venook et al., Yothers et al., Reimers et al., Yamanaka et al., and SUNRISE/SUNRISE-DI publications (see references).
ctDNA studies and reviews: ctDNA analytic and clinical studies and reviews include Tie et al. (NEJM 2022) and NCI task force and other evaluations of methylated BCAT1/IKZF1 and ctDNA for recurrence detection and adjuvant guidance (see references).

Coding

Covered CPT CodesCPTCovered

81525

Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes content and 5 housekeeping) , utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a recurrence score

ICD-10 Diagnosis CodesICD-10

C18.0-C20	Malignant neoplasm of colon to rectum
C21.1	Malignant neoplasm of anus and anal canal

Provider Actions & Billing Guidance

Prior Authorization

Prior authorization is not required for services covered by this policy. Ordering physicians remain responsible for any authorization, appeal, or other administrative processes related to authorization/medical necessity; laboratories and third parties are not permitted to obtain authorizations on behalf of the ordering physician.

Not applicable (no prior authorization required)

Note

Eligibility / Benefits Verification

Providers must verify member benefits and eligibility prior to providing services. Benefits and eligibility are determined by the member's subscriber agreement or certificate; contact the Blue Cross Blue Shield of Rhode Island provider services number to verify coverage for the planned service.

Verify benefits/eligibility via provider call center
Coverage determined by member-specific subscriber agreement/certificate

Not Covered

Specific genetic testing services may be excluded from coverage for some groups because of contract-level exclusions. Refer to the member's Benefit Booklet to confirm whether a particular test is covered, subject to authorization, considered not medically necessary, or specifically not covered under the group's contract.

Background

Gene expression profiling (GEP) assays and circulating tumor DNA (ctDNA) tests have been developed as prognostic markers to identify patients with stage II or stage III colon cancer who are at higher risk of recurrence after surgical resection. These tests, including commercially available assays such as the 12‑gene expression score, are intended to supplement standard clinicopathologic risk factors (for example, T4 tumors, obstruction/perforation, inadequate lymph node sampling, aggressive histology, or positive margins) to inform decisions about adjuvant chemotherapy. Laboratory-developed tests must meet CLIA high-complexity requirements when offered by a clinical laboratory.

Definitions

Oncotype DX Colon (CPT 81525)

AssayOncotype DX Colon — an mRNA gene expression profiling assay for colon cancer (commercially available from Genomic Health)

CPT code81525 — Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (and 5 housekeeping), algorithm reported as a recurrence score

Intended usePrognostic test to predict recurrence risk in stage II or III colon cancer following surgical resection to inform adjuvant chemotherapy decisions

AvailabilityCommercial service (Oncotype DX Colon) and may be offered as a laboratory-developed test under CLIA high-complexity laboratory licensing

Laboratory‑Developed Test (LDT)

DefinitionLaboratory-developed test (LDT): a clinical laboratory–developed and validated in-house test offered as a laboratory service

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyGene Expression Profile Testing and Circulating Tumor DNA Testing for Predicting Recurrence in Colon Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective Date01 01 2024

Next Review DateN/A

Key ActionOrdering physician must be involved in authorization and administrative processes; laboratories may not obtain authorization on behalf of the ordering physician.

SourceLink

On This Page

Guidelines and reviews: Relevant guideline and review citations include ASCO guideline update, AHRQ technical brief, Washington State Health Care Authority review, and NCI task force whitepaper (references listed).

References

References related to use of 12-gene recurrence score and ctDNA for recurrence risk assessment and guiding adjuvant therapy in stage II/III colorectal cancer — validation, impact studies, and guideline/review citations (listed for reference; do not establish additional coverage requirements).

Reference list (select): Venook et al.; Yothers et al.; Reimers et al.; Yamanaka et al.; SUNRISE and SUNRISE-DI impact studies; Tie et al. (NEJM 2022); NCI task force whitepaper; ASCO guideline update; AHRQ technical brief; Washington State Health Care Authority review; multiple ctDNA and methylated DNA analytic studies.

Note

Contract-Specific Exclusions

Coverage and benefits may vary by contract. Some groups have contract exclusions for expanded biomarker or genetic testing coverage per the Rhode Island mandate and employer agreements. Providers should refer to the member's benefit booklet and applicable proprietary laboratory analysis/genetic testing policies to determine if services require authorization, are covered, or are contract exclusions.

Some employer groups may exclude expanded biomarker/genetic testing coverage
Refer to the member's Benefit Booklet and related Genetic Testing / PLA policies

Denial Risk

Ordering Physician Involvement and Liability

Only the ordering physician shall be involved in authorization, appeals, or other administrative processes related to authorization/medical necessity. Laboratories or their representatives may not obtain authorization on behalf of the ordering provider. If a laboratory provides a service that was not authorized, BCBSRI will deny payment and may hold the laboratory financially liable. Services determined not medically necessary or non-covered may not be billed to the member unless the member was informed and provided written consent in advance.

Laboratories and third parties may not obtain authorizations for ordering physicians
Unauthorized lab-obtained services will be denied and may be the laboratory's financial liability
Do not bill members for non-covered or not medically necessary services unless informed and consent obtained in writing

Regulatory contextLDTs must meet Clinical Laboratory Improvement Amendments (CLIA) general regulatory standards and laboratories offering LDTs must be licensed for CLIA high‑complexity testing

Examples in policyMultigene expression panels and ctDNA assays for predicting recurrent colon cancer may be offered as LDTs under CLIA high-complexity oversight

12‑Gene Recurrence Score

Definition12‑gene recurrence score: a gene expression assay that generates a recurrence score used to estimate risk of recurrence in stage II and III colon (and rectal) cancer

Validation evidenceValidated in multiple studies including CALGB 9581, NSABP C‑07, and SUNRISE (see referenced validation studies)

Clinical impactStudies report the assay can influence adjuvant chemotherapy decision‑making in stage II/III colon cancer

Circulating Tumor DNA (ctDNA)

DefinitionCirculating tumor DNA (ctDNA): tumor‑derived DNA detectable in blood used as a biomarker for colorectal cancer recurrence detection

Clinical roleUsed in studies for detection of post‑surgery recurrence and to guide adjuvant therapy decisions in stage II colon cancer (eg, Tie et al. NEJM 2022)

Assay types referencedIncludes assays for methylated BCAT1/IKZF1 and broader ctDNA sequencing approaches cited in policy references