ModifiedBlue Cross Blue Shield - TexasPolicy CPCPLAB037

Serum Tumor Markers for Malignancies

This policy defines reimbursement criteria for measurement of serum tumor markers for various malignant indications and specifies which marker uses, frequencies, and indications may be reimbursable under the Plan. It applies to providers submitting claims to Blue Cross Blue Shield of Texas for covered members and products (note: not all requirements apply to every product).

Policy Summary

PayerBlue Cross Blue Shield - Texas

PolicySerum Tumor Markers for Malignancies

Policy CodePolicy CPCPLAB037

Change TypeMultiple clinical indication expansionsnew billing code added

Effective DateAug 1, 2025

Next Review Date

Key ActionWhen billing after 10/01/2025, reference updated reimbursement information and include new code 0599U where applicable.

SourceLink

POLICY UPDATE CHANGES

Added CPT/HCPCS code 0599U effective 10/01/2025.

Expanded indications for multiple tumor markers to include additional ovarian cancer histologies (carcinosarcoma, clear cell, grade 1 endometrioid, mucinous neoplasms, low-grade serous) for monitoring/follow-up.

For beta-2 microglobulin (B2M), added indications for prognostic and/or therapy determination in chronic lymphocytic leukemia/small lymphocytic lymphoma.

Added workup indication for calcitonin (CALCA) for adenocarcinoma, anaplastic/undifferentiated epithelial tumors, and occult primary cancers.

Added indications for assessing prognosis and monitoring/follow-up with CA 15-3/27.29 and CA 19-9 for occult primary cancers.

Added small bowel adenocarcinoma 'at metastasis or recurrence' to other indications.

Added uterine neoplasms indication for CA-125 initial workup.

Added gallbladder cancer adjuvant-treatment indication (as clinically indicated) for CEA.

Added INHA (inhibin) indication for workup of adrenocortical carcinoma.

Added initial diagnostic indications for systemic mastocytosis including lactate dehydrogenase (LDH).

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2025-08-01most recent Effective Date in this document section

1new code added (0599U)

5+ovarian histologies added across multiple markers

multiplemarkers with defined reimbursable indications

40+CPT/HCPCS codes listed (not all-inclusive)

Reimbursable Tumor Marker Uses and Criteria

Reimbursable markers, indications, frequencies, and exclusions

Specific serum tumor markers are reimbursable for enumerated diagnostic, treatment-monitoring, and surveillance indications; quarterly measurement is permitted by default unless a marker-specific frequency is stated.

Reimbursable marker uses and limits

Alkaline phosphatase (ALP)

Indication = Bone neoplasms: Workup; During treatment; Surveillance
Indication = 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 NOS; liver/mediastinum/retroperitoneal mass
Ovarian/fallopian tube/primary peritoneal cancer: Initial workup; During primary chemotherapy; Monitoring/follow-up for complete response as clinically indicated
Testicular cancer (non-seminoma and pure seminoma): Post-diagnostic workup; Risk classification; Surveillance no more than every 2 months; Initial diagnostic workup (seminoma)

Beta human chorionic gonadotropin (beta-HCG)

Gestational trophoblastic neoplasia: Initial workup; During and post treatment (no more than weekly); Follow-up/surveillance (no more than monthly)
Occult primary: Additional workup for localized adenocarcinoma or carcinoma NOS; individuals <65 with testes presenting with retroperitoneal mass
Ovarian cancers and germ cell tumors: Initial workup; During primary chemotherapy; Monitoring/follow-up for complete response; Surveillance no more than every 2 months for first 2 years, then every 4 months years 3-5, then annually

Calcitonin (CALCA)

Medullary carcinoma: Additional workup; Post-surgical evaluation; Monitoring; Surveillance 2-3 months postoperative, then every 6-12 months
Multiple endocrine neoplasia type 2: At diagnosis (clinical evaluation) for medullary thyroid cancer
Occult primary (unknown primary cancer): Workup

CA 19-9

Ampullary adenocarcinoma: Workup; Surveillance every 3-6 months for 2 years, then every 6-12 months up to 5 years for resected stage I-III
Appendiceal adenocarcinoma: Workup to establish baseline; abnormal measurements should be trended
Extrahepatic cholangiocarcinoma/gallbladder/intrahepatic cholangiocarcinoma: Workup to establish baseline; Monitoring; Surveillance as clinically indicated
Occult primary: Assessing disease prognosis and monitoring/follow-up for response

CA-125

Appendiceal adenocarcinoma: Workup to establish baseline
Endometrial carcinoma: Additional workup; Surveillance if initially elevated
Lynch syndrome: Surveillance
Occult primary (uterus/ovaries present): Additional workup for adenocarcinoma or carcinoma NOS
Ovarian/fallopian tube/primary peritoneal cancer: Initial workup; During primary chemotherapy; Monitoring/follow-up for complete response as clinically indicated

CEA

Appendiceal adenocarcinoma: Workup to establish baseline; Monitoring; Post-treatment surveillance
Breast cancer (invasive): Monitoring metastatic disease
Colon cancer: Workup to establish baseline; Monitoring; Surveillance every 3-6 months for 2 years, then every 6 months for total of 5 years
Medullary carcinoma: Diagnosis and additional workup; Monitoring; Post-surgical surveillance 2-3 months postoperative, then every 6-12 months

Lactate dehydrogenase (LDH)

B-cell lymphomas: Workup
Bone neoplasms: Workup
Chronic lymphocytic leukemia/SLL: Workup and at transformation or histologic progression
Melanoma: Workup for metastatic or recurrent disease
Multiple myeloma: Initial workup; Surveillance as needed post primary treatment for solitary plasmacytoma

Serum free light chain

Multiple myeloma: Initial diagnostic workup; Surveillance up to once per month
Systemic light chain amyloidosis: Initial diagnostic workup

Other markers: Various other markers (e.g., INHA/inhibin, B2M, troponin T, tryptase) are reimbursable for specific workup, monitoring, staging, or surveillance indications as enumerated in the policy text (marker-specific uses apply)

ALL of the following

For all other cancer indications not discussed above, use of the above biomarkers (alone or in a panel) are 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.

ALL of the following

Default: quarterly measurement permitted for follow-up, monitoring, and surveillance unless otherwise specified
Marker-specific frequency examples: AFP surveillance every 3-6 months for 2 years then every 6 months; CA 19-9/CA-125/CEA surveillance schedules and beta-HCG/testicular surveillance limits as enumerated above; serum free light chain surveillance up to once per month

Providers must use the marker- and indication-specific guidance in the policy when submitting claims; documentation should support the indicated clinical use and frequency.

Operational

Reference list (no coverage rules in this part)

References supporting clinical utility, diagnostic, prognostic, and guideline-based uses of tumor markers are listed below; no direct coverage rules are contained in this section.

See References section for citations including guideline and evidence sources (examples): ACS on Waldenström macroglobulinemia; ADLM Serum Free Light Chains guidance; ATA MTC guidelines; NCCN Biomarkers Compendium and NCCN guidelines; peer-reviewed studies on B2M and serum free light chains

Updated coverage criteria (summary)

Summary of coverage changes and added clinical indications from Policy Update History entries in this document segment.

Added code 0599U effective 10/01/2025 (billing update)

AFP and multiple other markers: expanded monitoring/follow-up indications to include additional ovarian cancer histologies and removal of '(less common)' designation

Beta-2 microglobulin (B2M): added prognostic and therapy-determination indications for chronic lymphocytic leukemia/small lymphocytic lymphoma

Calcitonin (CALCA): added workup indication for adenocarcinoma, anaplastic/undifferentiated epithelial tumors, and occult primary

CA 15-3/27.29 and CA 19-9: added indications for assessing prognosis and monitoring/follow-up in occult primary cancers

Procedure Codes and Billing Frequency

Listed procedure codesmixed

81500
81503
81538
81599
82105
82107
82232
82308
82378
83520

1–10 of 36

1/4

No billing codes provided in this sectionmixed

No codes listed

Recently added codesCPT

0599U

New code added to policy effective 10/01/2025

Surveillance frequency default

Default surveillance frequencyQuarterly measurement of designated serum tumor markers is permitted for follow-up, monitoring, and/or surveillance unless otherwise specified in the policy.

Exception basisMarker- and indication-specific frequency limits supersede the quarterly default when explicitly stated in the table.

Typical uses covered by default frequencyFollow-up, monitoring, and surveillance of reimbursable serum tumor markers.

Non-applicability noteWhere a different interval is listed for a specific marker/indication, that interval applies instead of the quarterly default.

Serum free light chain surveillance frequency for multiple myeloma

Documentation, Claims, and Provider Guidance

Documentation Required

Documentation and claims review — providers responsible for submission of accurate documentation and providing additional documentation on request

Providers are responsible for submission of accurate documentation of services performed and for coding claims using valid HIPAA-approved code sets. Claims are subject to code edit protocols and review against benefit coverage, provider contract language, medical policies, clinical payment and coding policies, and coding software logic. Upon request, providers must submit additional documentation to support medical necessity, coding, and billing. Providers should follow industry-standard coding guidelines (Uniform Billing, AMA CPT and CPT Assistant, HCPCS, ICD-10-CM/PCS, NDC, DRG guidelines, CMS NCCI Policy Manual and CCI edits).

Submit complete medical records and supporting documentation when requested.
Ensure claims use appropriate, up-to-date codes and modifiers per industry guidance.
Be prepared for claim review and provide additional documentation promptly upon request.

Note

References and citations — notes that this references section contains citations only and no explicit prior authorization or billing rules

References cited in this policy are provided for clinical background and evidence support only. They do not establish prior authorization, coverage, or billing rules by themselves. Providers should rely on the policy text, code tables, and Policy Update History for the operative coverage and billing requirements.

Definitions and Guideline Context

Plan documents

Governing documentsPlan documents (e.g., Certificates of Health Care Benefits, benefit booklets, Summary Plan Descriptions) govern if a conflict arises with this policy.

Provider contractsIf a conflict arises between this policy and a provider contract, the provider contract will govern.

Plan discretionBlue Cross and Blue Shield of Texas may use reasonable discretion interpreting and applying this policy; BCBSTX has final discretionary authority as provided under plan documents.

Serum free light chains — assay references and diagnostic ranges

Assay contextSerum free light chain assays and referenced diagnostic ranges (free kappa and free lambda) are described in the literature for detection of monoclonal light chains and diagnostic sensitivity.

Diagnostic ranges reference

Policy Summary

PayerBlue Cross Blue Shield - Texas

PolicySerum Tumor Markers for Malignancies

Policy CodePolicy CPCPLAB037

Change TypeMultiple clinical indication expansionsnew billing code added

Effective DateAug 1, 2025

Next Review Date

Key ActionWhen billing after 10/01/2025, reference updated reimbursement information and include new code 0599U where applicable.

SourceLink

On This Page

CA-125: added monitoring/follow-up indications for multiple ovarian histologies and added initial workup indication for uterine neoplasms

CEA: added adjuvant-treatment monitoring indication for gallbladder cancer and expanded ovarian histology monitoring additions

INHA (Inhibin): added workup indication for adrenocortical carcinoma and ovarian histology monitoring additions

LDH: added monitoring/follow-up indications for multiple ovarian histologies and added initial diagnostic indications for systemic mastocytosis

Small bowel adenocarcinoma: added indication 'at metastasis or recurrence'

SFLc surveillance interval (multiple myeloma)

Serum free light chain surveillance for multiple myeloma: up to once per month.

Diagnostic usesSerum free light chain may be used for initial diagnostic workup of multiple myeloma and systemic light chain amyloidosis.

Related markers for amyloidosisTroponin T is listed for initial diagnostic workup of systemic light chain amyloidosis alongside serum free light chain.

None specified in these chunks

No explicit threshold providedNo specific value or frequency was specified in these chunks for the requested item.

InterpretationUse the policy text or marker-specific rows elsewhere in the document to determine applicable limits when not stated here.

Action for providersSubmit supporting documentation when ordering tests with unspecified frequency to justify medical necessity per plan documents.

Billing Rule

Policy update / billing implication — Policy Update History documents coding and coverage revisions; providers should reference updates and newly added codes

Policy Update History documents coding and coverage revisions; providers must review the Policy Update History to identify new or changed codes, effective dates, and any reimbursement implications. Recent updates include addition of CPT code 0599U effective 10/01/2025 and multiple reimbursement information changes to tumor marker indications (see Policy Update History for full details). When billing, use the code sets and effective dates specified in the Policy Update History and ensure documentation supports any medical necessity or indication changes noted.

Confirm and apply newly added codes and their effective dates when submitting claims (e.g., 0599U effective 10/01/2025).
Refer to Policy Update History for changes to test indications and reimbursement guidance (tumor marker and other lab test revisions).
Maintain documentation that supports any changed indications or monitoring/follow-up uses reflected in updates.

Katzmann et al. report serum reference intervals and diagnostic ranges for free kappa and free lambda light chains (Clin Chem 2002).

Clinical relevanceSerum free light chains are used for detection and monitoring of multiple myeloma and related conditions, and referenced in multiple cited reviews and guidance documents.

Clinical practice guidelines

NCCN guidanceNCCN Clinical Practice Guidelines and the NCCN Biomarkers Compendium are cited as sources for biomarker guidance in oncology.

Other guideline sourcesGuideline and society documents referenced include NANETS and specialty guidance cited in the references list.

Use as guidanceGuidelines are referenced as informational sources to inform clinical utility, diagnostic, prognostic, and monitoring roles of tumor markers in the policy.

Reference list

Comprehensive citationsReference list includes clinical studies and guideline documents (e.g., AASLD HCC guidance, NCCN guidelines, Clin Chem practice guidelines) supporting marker uses.

Serum free light chain literatureKey references include assay and clinical utility publications for serum free light chains and AL amyloidosis (e.g., Merlini et al., Katzmann et al.).

Tumor marker guideline sourcesReferences encompass National Academy of Clinical Biochemistry practice guidelines and society guidance relevant to tumor marker quality and use.

Policy update sourcesPolicy Update History entries documenting coding and coverage revisions are included in the reference section.