DraftBlue Cross Blue Shield - Rhode IslandPolicy N/A

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

Defines coverage stance for gene expression profiling (Oncotype DX Colon) and circulating tumor DNA tests as prognostic markers to predict recurrence after surgery in stage II and III colon cancer for Blue Cross Blue Shield - Rhode Island members.

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 changes

Effective DateJan 1, 2024

Next Review DateN/A

Key ActionVerify member benefits and file claims for CPT 81525 with an appropriate ICD-10 diagnosis code from C18.0-C20 or C21.1.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

81525CPT code specified for Oncotype DX Colon

Stage II/IIIClinical stages addressed

Medicare Adv & CommercialProducts named

CLIARegulatory standard

Coverage Criteria

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Medically Necessary Tests

The following GEP and ctDNA tests may be considered medically necessary for prognostic assessment following surgery in stage II or III colon cancer:

Medically necessary listing: Oncotype DX Colon (Genomic Health) CPT 81525 is considered medically necessary for Medicare Advantage Plans and Commercial Products for prognostic assessment following surgical resection in stage II or III colon cancer

Policy statement names this assay explicitly

Coverage for genetic testing services may be affected by contractual exclusions tied to the state Biomarker Testing Mandate (RI.G.L. 27-19-81). For commercial groups that have excluded the expanded biomarker-related coverage under their contract, certain genetic testing services may be treated as contract exclusions and therefore not covered. Providers should consult the member's Benefit Booklet or the related Genetic Testing Services / Proprietary Laboratory Analyses policies to determine whether a specific test is covered, requires authorization, or is excluded for that funded group.

The provided policy excerpt does not include a specific list of tests or clinical indications that are explicitly excluded. For member-specific exclusions or details about non-covered services, providers must verify benefits with the member's subscriber agreement and benefit documentation.

This draft indicates Medical Criteria: Not applicable, and does not present specific medical necessity criteria or condition-based rules for the tests described in the excerpt.

The excerpt does not contain explicit statements labeling any service as not medically necessary. Determinations about medical necessity and any resulting member liability are subject to the member's subscriber agreement and employer agreement.

Covered Indications

Prognostic testing after surgical resection to predict recurrence risk in stage II or III colon cancer

Prognostic testing after surgical resection to predict recurrence risk in stage II or III colon cancer may be considered when using the validated 12-gene recurrence score assay (Oncotype DX Colon).

Test and coding: Oncotype DX Colon (12-gene recurrence score assay; CPT 81525) is identified in this policy as the gene expression profiling test for prognostic assessment after surgery in stage II or III colon cancer

When billed, include an appropriate ICD-10 diagnosis code from C18.0-C20 or C21.1 as listed in coding guidance

Intended clinical use: Use of the 12-gene recurrence score is to stratify recurrence risk after surgical resection and inform consideration of adjuvant chemotherapy in stage II and stage III disease

Overview and policy statement specify prognostic use in stage II/III

Evaluation of recurrence risk and guidance of adjuvant chemotherapy decisions in stage II/III colon cancer

Published studies support the use of multigene expression profiling and ctDNA assays to evaluate recurrence risk and to inform adjuvant chemotherapy decisions in stage II/III colon cancer:

Clinical evidence for 12-gene recurrence score: Multiple studies (e.g., SUNRISE, SUNRISE-DI, prospective impact studies) demonstrate that the 12-gene recurrence score stratifies recurrence risk and influences adjuvant chemotherapy recommendations in stage II/III colon cancer

See referenced literature (Yamanaka et al., Oki et al., Brenner et al., Cartwright et al., Srivastava et al.)

Clinical evidence for ctDNA methylation assays: Studies assessing detection of methylated BCAT1 and IKZF1 in circulating tumor DNA report associations between post-surgery ctDNA detection and increased risk of residual disease and lower recurrence-free survival, supporting use of ctDNA assays to detect residual disease and recurrent colorectal cancer

See referenced literature (Murray et al., Young et al., Musher Melson et al., Symonds et al.)

Interpretation considerations: Clinical and pathologic features (including microsatellite instability and mismatch repair status) and the limits of existing high-risk feature definitions should be considered when applying assay results to adjuvant therapy decisions

Background and evidence summaries note potential confounding clinical factors

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

Associated ICD-10 diagnosis codesICD-10

C18.0-C20	Malignant neoplasms of colon through rectum (ICD-10 range as listed)
C21.1	Malignant neoplasm of anus and anal canal

Number of lymph nodes examined — threshold

Number of lymph nodes examinedLess than 12 sampled lymph nodes at surgery is identified as an inadequately low number of sampled lymph nodes (< 12)

Clinical significanceAn inadequate lymph node count (< 12) is listed among pathologic features used to identify high‑risk stage II colon cancer

Impact on adjuvant decisionsAn inadequately low lymph node count may contribute to classification as high‑risk disease and influence consideration of adjuvant chemotherapy

Provider Actions

Prior Authorization

Prior Authorization Required

Prior authorization: Not applicable per this policy excerpt. Medicare Advantage Plans and Commercial Products: Oncotype DX Colon (Genomic Health) is listed as medically necessary for Medicare Advantage and commercial products when billing requirements are met.

Affected code: CPT 81525 — see coding block for required ICD-10 codes
Verify member-specific benefits and contract exclusions in the member's Benefit Booklet or Evidence of Coverage; employer/group contract provisions may supersede policy (source chunks 6,7,20)

Documentation Required

Benefit Verification

Verify member eligibility and benefits in the appropriate Benefit Booklet, Evidence of Coverage, or Subscriber Agreement prior to ordering testing. Some commercial groups may have contract exclusions for expanded biomarker/genetic testing per state or group-specific mandates; check related Genetic Testing Services or Proprietary Laboratory Analyses policies for details.

For member-specific benefit questions call the provider call center (source chunk 20)

Billing Rule

Coding / Claim Filing

When billing CPT 81525, include an appropriate ICD-10 diagnosis code from the range C18.0-C20 or C21.1. Failure to submit an applicable diagnosis code may result in claim denial.

CPT 81525 — file with ICD-10 C18.0-C20 or C21.1

Denial Risk

Member Agreement and Medical Necessity

Coverage and payment are determined by the member's subscriber agreement and employer contract; services deemed not medically necessary or non-covered per those agreements may be denied. Providers must inform members in writing if services will be rendered at the member's expense when non-covered.

Benefits documents supersede this policy
Obtain written member agreement before providing non-covered services

Not Covered

For some commercial groups, specific genetic testing services may be explicitly not covered when those services are contract exclusions under the Biomarker Testing Mandate. Whether a particular test is excluded depends on the group's contract language; providers should review the member's Benefit Booklet or the related Genetic Testing Services policies to determine coverage for the funded group in question.

The excerpt does not provide a named list of tests or indications that are explicitly excluded from coverage. For definitive exclusion lists, consult the member’s subscriber agreement, benefit booklet, or the related policy documents referenced by the plan.

Definitions

12‑gene recurrence score assay for colon cancer (CPT 81525)

Test name and CPTOncotype DX Colon — CPT 81525 (Oncology (colon), mRNA, 12‑gene expression profiling)

Manufacturer/ProviderGenomic Health (Oncotype DX Colon)

Clinical usePrognostic gene expression profiling to assess recurrence risk after surgery in stage II/III colon cancer

Laboratory‑developed test (LDT)

DefinitionLaboratory‑developed tests (LDTs) are tests developed and validated in‑house by clinical laboratories and offered as laboratory services

Regulatory standardLDTs must meet Clinical Laboratory Improvement Amendments (CLIA) general regulatory standards

FDA reviewLDTs may be offered without additional FDA premarket review as noted in the policy

12‑gene recurrence score

Assay description12‑gene recurrence score is a multigene expression assay that stratifies recurrence risk in stage II and III colon cancer

Evidence baseReferenced in multiple studies (e.g., SUNRISE study) demonstrating stratification of recurrence risk and impact on adjuvant chemotherapy decisions

Genes includedAssay reported as a recurrence score derived from expression of 12 genes (plus housekeeping genes) as used in Oncotype DX Colon

methylated BCAT1/IKZF1 circulating tumor DNA (ctDNA)

Biomarker targetsDetection of methylation of BCAT1 and IKZF1 in circulating tumor DNA (ctDNA)

Clinical applicationUsed to detect residual disease and recurrent colorectal cancer after surgery

Supporting studiesMultiple referenced studies evaluate post‑surgery detection of methylated BCAT1/IKZF1 ctDNA and association with residual disease and recurrence risk

Background

Stage II and III colon cancer are managed primarily with surgical resection; adjuvant chemotherapy is considered for high-risk stage II disease and for stage III disease. Gene expression profiling and circulating tumor DNA (ctDNA) tests are intended to help identify patients at increased risk of recurrence after surgery to inform adjuvant chemotherapy decisions. Clinical and pathologic features (for example, tumor substage including T4a/T4b, obstruction or perforation at diagnosis, number of lymph nodes examined < 12, aggressive histologic features, and margin status) are commonly used to assess risk, but their ability to identify which patients will clearly benefit from adjuvant therapy is limited. Microsatellite instability and mismatch repair deficiency may confound interpretation and affect expected benefit from fluorouracil-based regimens, so these factors should be considered when using gene expression or ctDNA test results to guide treatment decisions.

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