Blue Cross Blue Shield Illinois serum tumor markers Coverage

Coverage Criteria — Reimbursable Indications and Scope

Reimbursable serum biomarker indications and surveillance

Measurement of specified serum biomarkers may be reimbursable for the listed cancer-related indications and surveillance schedules; biomarkers or indications not listed are not reimbursable.

Except where otherwise specified, quarterly measurement of designated serum biomarkers is permitted for follow-up, monitoring, and/or surveillance.

Alkaline phosphatase (ALP)

Bone neoplasms: workup.
Melanoma (uveal): workup.
Systemic light chain amyloidosis: initial diagnostic workup.

Alpha fetoprotein (AFP)

Hepatocellular carcinoma: screening; workup for confirmed HCC; surveillance (every 3-6 months for 2 years, then every 6 months).
Intrahepatic cholangiocarcinoma: workup for isolated intrahepatic mass.
Occult primary: additional workup for localized adenocarcinoma or carcinoma not otherwise specified; liver, mediastinum, or retroperitoneal mass.
Ovarian cancer/fallopian tube cancer/primary peritoneal cancer: initial workup; during primary chemotherapy; monitoring/follow-up for complete response (as clinically indicated).
Less common ovarian cancers (carcinosarcoma, clear cell carcinoma): monitoring and follow-up as indicated.

Ovarian and related biomarkers (general ovarian indications)

Mucinous neoplasms of the ovary: monitoring and follow-up.
Low-grade serous carcinoma: monitoring and follow-up.
Borderline epithelial tumors: monitoring/follow-up (every visit if initially elevated).
Malignant germ cell tumors: surveillance (no more than every 2 months for the first 2 years, every 4 months in years 3–5, then annually after year 5).
Malignant sex cord stromal tumors: surveillance if clinically indicated; frequency based on stage (6–12 months if early-stage low-risk; 4–6 months if high-risk).

Cancer antigen 125 (CA-125)

Post-treatment surveillance (every 3–6 months for 2 years, then every 6 months for a total of 5 years).
At metastasis or recurrence.
Occult primary: initial evaluation/workup; additional workup for adenocarcinoma or carcinoma not otherwise specified in those with a uterus and/or ovaries present.

Cancer antigen 19-9 (CA 19-9)

Initial diagnostic workup and establishing baseline for ampullary, appendiceal, extrahepatic and intrahepatic cholangiocarcinoma, gallbladder cancer and pancreatic adenocarcinoma; monitoring and surveillance as clinically indicated (for resected ampullary cancer: every 3–6 months for 2 years, then every 6–12 months up to 5 years).
Abnormal measurements should be trended.

Carcinoembryonic antigen (CEA)

Colon cancer: workup to establish baseline; monitoring; surveillance (every 3–6 months for 2 years, then every 6 months for a total of 5 years).
Breast cancer (invasive): monitoring metastatic disease.
Workup/monitoring for appendiceal, uterine, intrahepatic cholangiocarcinoma, gallbladder cancer, peritoneal mesothelioma as clinically indicated.

Chorionic gonadotropin beta polypeptide (CGB3)

Gestational trophoblastic neoplasia: initial workup; during and post treatment (no more than weekly); follow-up/surveillance (no more than monthly for 12 months).
Occult primary: additional workup for localized adenocarcinoma.

Serum free light chains

Surveillance: no more than every 2 months for the first 2 years, every 4 months in years 3–5, then annually after year 5.
Multiple myeloma: initial diagnostic workup; follow-up; surveillance (up to once per month).
Malignant sex cord stromal tumors: surveillance if clinically indicated with frequency based on stage (6–12 months early-stage low-risk; 4–6 months if high-risk).

Calcitonin (CALCA)

Initial diagnostic workup for medullary carcinoma and related indications; additional workup; post-surgical evaluation; monitoring; surveillance (2–3 months postoperative, then every 6–12 months).
At diagnosis for multiple endocrine neoplasia, type 2 (clinical evaluation).

Other biomarkers (examples)

BNP or NT-proBNP: initial diagnostic workup.
Beta-2 microglobulin (B2M): workup for B-cell lymphomas, Castleman disease, chronic lymphocytic leukemia/small lymphocytic lymphoma (including prognostic/therapy determination), and multiple myeloma (initial diagnostic workup; follow-up/surveillance as needed for solitary plasmacytoma).
Troponin T: initial diagnostic workup for systemic light chain amyloidosis.
Tryptase: initial diagnosis for systemic mastocytosis.

For all other cancer indications not discussed above, use of the above biomarkers (alone or in a panel) is not reimbursable; all other serum tumor markers not addressed above (alone or in a panel) are not reimbursable; analysis of proteomic patterns in serum for screening and detection of cancer is not reimbursable.

Coverage scope and codes

Lists covered test codes and policy update history; a new policy effective 09/05/2025 with implementation noted for 01/01/2026.

The following CPT/HCPCS and other test codes are listed as relevant to this policy: 81500, 81503, 81538, 81599, 82105, 82107, 82232, 82308, 82378, 83520, 83521, 83789, 83880, 83950, 83951, 84075, 84078, 84080, 84484, 84702, 84703, 84704, 84999, 86300, 86301, 86304, 86305, 86316, 86336, 0003U, 0092U, 0163U, 0404U, 0558U, 0559U, 0599U, G0327.

Policy Update History: 09/05/2025, Effective Date; Summary of Changes = 01/01/2026: New policy.

Coding — Procedure and Test Codes

Listed procedure codesCPT

81500
81503
81538
81599
82105
82107
82232
82308
82378
83520

1–10 of 37

1/4

listed laboratory and molecular test codesmixed

81500
81503
81538
81599
82105
82107
82232
82308
82378
83520

1–10 of 37

1/4

Surveillance frequency (examples)

Typical surveillance exampleEvery 3–6 months for the first 2 years, then every 6–12 months up to 5 years as clinically indicated

Germ cell tumor exceptionSome germ cell tumor monitoring may have shorter intervals; specific guidance notes ‘no more than every 2 months’ for certain indications

Initial post-treatment periodQuarterly measurement is permitted for designated serum biomarkers for follow-up, monitoring, and/or surveillance unless otherwise specified

Long-term surveillanceAfter initial 2-year period, surveillance frequency commonly decreases to every 6–12 months depending on cancer type and clinical judgment

Provider Actions — Documentation and Billing Guidance

Documentation Required

Documentation and claim review expectations

Providers are responsible for submission of accurate documentation of services performed and must code claims using valid HIPAA-approved code sets and industry-standard coding guidelines. Claims are subject to code edit protocols and claim review; upon request, providers are urged to submit any additional documentation to support the claim.

Billing Rule

Test and billing codes

The following procedure and laboratory test codes are relevant to this policy and should be used when billing the listed serum biomarker services: 81500, 81503, 81538, 81599, 82105, 82107, 82232, 82308, 82378, 83520, 83521, 83789, 83880, 83950, 83951, 84075, 84078, 84080, 84484, 84702, 84703, 84704, 84999, 86300, 86301, 86304, 86305, 86316, 86336, 0003U, 0092U, 0163U, 0404U, 0558U, 0559U, 0599U, G0327.

Use HIPAA-approved code sets and appropriate code combinations per industry coding guidelines when submitting claims.

Definitions and Test Background

Plan documents and Covered Services

Definition of Plan documentsIncludes Certificates of Health Care Benefits, benefit booklets, Summary Plan Descriptions, and other coverage documents; plan documents govern when conflicts arise with policy

Covered Services governanceIf a conflict arises between this policy and a plan document under which a member is entitled to Covered Services, the plan document will govern

Provider responsibilityProviders must submit accurate documentation and appropriate codes; claims are subject to code edit protocols and claim review as described in plan documents

Serum biomarkers

Serum biomarkers definedBiochemical substances measured in blood that may reflect tumor presence or behavior (commonly called tumor markers)

Authoritative sources

OpenPayer

Serum Tumor Markers for Malignancies

Coverage Criteria — Reimbursable Indications and Scope

Coding — Procedure and Test Codes

Provider Actions — Documentation and Billing Guidance

Definitions and Test Background