Tumor marker and molecular marker testing for cancer — coverage criteria
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This policy lists common cancer types and associated tumor markers, relevant CPT codes, and notes when marker results are necessary for safe or effective use of therapy; it applies to providers ordering tumor/molecular marker testing for oncology patients covered by Highmark Delaware.
No material clinical or coverage changes in this revision.
Coverage criteria for tumor and molecular marker testing
General coverage criteria
Covered when ALL of the following are met:
See test-specific criteria referenced in the table for details.
The table of tumor and molecular markers included in this policy is not all‑inclusive. Tests or markers that are not listed in the table are subject to test‑specific criteria or separate policies and are not automatically covered.
Use of tumor markers for indications that are not supported by the relevant test‑specific criteria or that are not related to FDA‑labeled therapy guidance may be considered not medically necessary under the applicable policy and therefore may not be covered.
Covered indications where tumor markers guide therapy or prognosis
Examples of metastatic cancers and associated tumor markers
Examples of covered metastatic cancers and associated tumor markers
- Melanoma (metastatic): BRAF — (see test-specific criteria); associated treatments include vemurafenib, dabrafenib, trametinib (and combinations).
Applicable policy: test-specific criteria.
- Non-small cell lung cancer (metastatic): EGFR — CPT 81235; ALK — CPT 81401 or 81479; associated FDA‑labeled treatments include crizotinib, ceritinib, and alectinib for ALK-positive disease.
When an associated FDA‑labeled therapy exists, the marker result is necessary for safe/effective use (companion diagnostic).
Example CPT and procedure codes
Provider requirements, prior authorization, and documentation
Prior Authorization Required
Prior authorization is required per the test-specific criteria before ordering molecular tumor marker testing when indicated by policy.
- Applies to tests listed under test-specific criteria (e.g., KRAS, NRAS, BRAF, EGFR, ALK where referenced).
- Prior auth must be obtained when the test is being used to guide therapy selection for FDA‑labeled treatments (companion diagnostics).
Obtain prior authorization and include clinical information demonstrating medical necessity. If the test result is required to determine eligibility for an FDA‑labeled therapy (companion diagnostic), document how results will be used to guide treatment.
- Include cancer type, stage (e.g., metastatic / stage IV), and prior treatments in the request.
- When testing is performed to select targeted therapy (for example, KRAS/NRAS for anti-EGFR therapy in metastatic colorectal cancer; BRAF for BRAF inhibitors in metastatic melanoma; EGFR/ALK for targeted NSCLC agents), specify the intended associated therapy.
- If claim code or CPT differs by marker, include the specific test name or CPT (e.g., 81275 for KRAS, 81311 for NRAS, 81210 for BRAF, 81235 for EGFR, 81401/81479 for ALK as applicable).
Documentation Required When Testing Guides Therapy
When test results will directly guide therapy, submit documentation with the claim or prior authorization showing how the result will affect management. Acceptable documentation includes pathology reports, treatment plan notes, and documentation of the targeted therapy being considered.
- Pathology report confirming diagnosis and stage (e.g., metastatic / stage IV).
- Progress notes that state the treatment decision depends on the molecular result.
- Order form or treatment plan naming the intended FDA‑labeled drug linked to the marker (e.g., cetuximab or panitumumab for RAS wild-type colorectal cancer; vemurafenib or dabrafenib for BRAF‑mutant melanoma; crizotinib/ceritinib/alectinib for ALK‑positive NSCLC).
Companion Diagnostic / Denial Risk
Companion diagnostic requirement: failure to document that a molecular test result is required for safe/effective use of an FDA‑labeled therapy may result in denial of coverage.
- Tests tied to an associated FDA‑labeled treatment (listed in policy tables) are considered companion diagnostics; provide documentation showing the therapy is being considered.
- If no documentation links the test to treatment selection, the service may be reviewed as not medically necessary and denied.
Key definitions
Background and clinical context
Tumor and molecular markers are assays used in metastatic cancers both for prognostic information and to identify patients eligible for targeted therapy. Common examples referenced in this policy include BRAF, KRAS, NRAS, EGFR, and ALK, which are listed with typical clinical contexts (for example, BRAF in metastatic colorectal cancer or melanoma; KRAS/NRAS in metastatic colorectal cancer; EGFR and ALK in non‑small cell lung cancer).
Not covered / exclusions
Tests or tumor markers that are not listed in the policy table or that do not meet the applicable test‑specific criteria require review and are not automatically covered. Providers should follow the referenced test‑specific policy or submit supporting clinical documentation for review when ordering markers outside the table.
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