ModifiedBlue Cross Blue Shield - New MexicoPolicy CPCPLABO37

Serum Tumor Markers for Malignancies

This document governs reimbursement criteria and allowable indications for serum tumor marker testing for Blue Cross Blue Shield of New Mexico members and applies to providers submitting claims under applicable plan documents.

Policy Summary

PayerBlue Cross Blue Shield - New Mexico

PolicySerum Tumor Markers for Malignancies

Policy CodePolicy CPCPLABO37

Change TypeAdded codesexpanded/revised indications and monitoring frequencies

Effective DateOct 1, 2025

Next Review DateN/A

Key ActionReference the updated reimbursement table and use new code 0599U where applicable; follow revised monitoring frequencies (e.g., 'every visit' for borderline ovarian epithelial tumors if initially elevated).

SourceLink

POLICY UPDATE CHANGES

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

Expanded indications for multiple tumor markers (AFP, CA-125, CA19-9, CA15-3/27.29, B2M, CALCA, inhibin, LDH, beta-HCG and others) including additions for various ovarian tumor subtypes, occult primary cancers, ampullary adenocarcinoma surveillance, and systemic mastocytosis workup.

Frequency of monitoring for some markers (e.g., AFP and beta-HCG for borderline ovarian epithelial tumors) was clarified (from every 3-6 months to 'every visit' if initially elevated; beta-HCG surveillance frequencies specified).

Removed several prior indications such as certain initial diagnostic evaluations for sacrococcygeal teratomas, testicular nonseminoma (initial), and uveal melanoma metastasis evaluation for ALP.

Added indications for carcinosarcoma (malignant mixed mullerian tumors), clear cell carcinoma of the ovary, grade endometrioid carcinoma, mucinous neoplasms, and low-grade serous carcinoma for monitoring/follow-up.

1new code added (0599U) effective 10/01/2025

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Reimbursable Markers, Indications, and Updates

Marker-specific coverage updates

Marker-specific coverage updates — per-marker, per-diagnosis indications (added, removed, frequency revised) for monitoring, surveillance, initial diagnosis and follow-up.

ALL of the following

Alkaline phosphatase (ALP): For bone neoplasms, added indications for measurement during treatment and surveillance.
Alkaline phosphatase (ALP): For uveal melanoma, removed indication for initial diagnostic evaluation for metastatic or recurrent disease.

ALL of the following

Alpha fetoprotein (AFP): For ovarian cancers (borderline epithelial tumors), updated frequency for monitoring/follow-up from every 3-6 months to every visit if initially elevated.
Alpha fetoprotein (AFP): For occult primary cancers, updated specification from initial diagnostic evaluation to additional workup.
Alpha fetoprotein (AFP): For sacrococcygeal teratomas and testicular cancer (nonseminoma), removed indications for initial diagnostic evaluation where noted in prior versions.

ALL of the following

Beta-2 microglobulin (B2M): For chronic lymphocytic leukemia/small lymphocytic lymphoma, added indication for prognostic and/or therapy determination.
Beta-2 microglobulin (B2M): For Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma, removed indication for prognostication at the time of first-line treatment initiation (prior versions).

ALL of the following

Beta human chorionic gonadotropin (beta-HCG): For gestational trophoblastic neoplasia, added indications for initial workup; during and post treatment (no more than weekly); follow-up/surveillance (no more than monthly for 12 months).
Beta human chorionic gonadotropin (beta-HCG): For occult primary cancers, updated specification from initial diagnostic evaluation to additional workup; for borderline ovarian epithelial tumors, updated frequency for monitoring/follow-up to every visit if initially elevated; for sacrococcygeal teratomas and testicular nonseminoma, removed initial diagnostic indications where previously listed.

ALL of the following

BNP or NT-proBNP: For multiple myeloma, added indication for initial diagnostic workup.

ALL of the following

Calcitonin (CALCA): For medullary carcinoma, replaced indication for initial diagnostic evaluation with indication for additional workup and added indication for post-surgical evaluation; for adenocarcinoma and anaplastic/undifferentiated epithelial tumors, added indication of workup; for occult primary (unknown primary cancer), added indication for workup.

ALL of the following

Cancer antigen 15-3 and 27.29 (CA 15-3 and 27.29): For occult primary cancers (cancers of unknown primary origin), added indications for assessing disease prognosis and monitoring/follow-up for response; added monitoring indications where noted in ovarian cancer subtypes updates.

ALL of the following

Cancer antigen 19-9 (CA 19-9): Added ampullary adenocarcinoma and indications for its workup; surveillance schedule for resected ampullary cancer: every 3-6 months for 2 years, then every 6-12 months for up to 5 years as clinically indicated. Added appendiceal adenocarcinoma (baseline workup) and added indications for occult primary cancers for assessing prognosis and monitoring/follow-up for response; ovarian and pancreatic indications clarified.

ALL of the following

Cancer antigen 125 (CA-125): For appendiceal adenocarcinoma, added indication for workup to establish baseline; added Lynch syndrome surveillance/prevention strategies; for borderline ovarian epithelial tumors, updated frequency for monitoring/follow-up to every visit if initially elevated; for mucinous carcinoma of the ovary, removed specification for initial diagnostic evaluation but retained indication for additional workup if not previously done.

ALL of the following

Carcinoembryonic antigen (CEA): For appendiceal adenocarcinoma, added indications for workup to establish baseline, monitoring, and post-treatment surveillance; for colon cancer, extrahepatic cholangiocarcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and medullary carcinoma, added indication for monitoring; removed several prior non-recommended indications (e.g., NSCLC, pleural/peritoneal mesothelioma) in earlier reorganizations.

ALL of the following

Inhibin (INHA): For adrenocortical carcinoma added indication for workup; for ovarian cancers (borderline ovarian epithelial tumors and other subtypes) updated frequency for monitoring/follow-up to every visit if initially elevated; removed indication for undiagnosed pelvic masses initial diagnostic evaluation where specified previously.

ALL of the following

Lactate dehydrogenase (LDH): For multiple malignancies including ovarian cancer subtypes, added monitoring/follow-up indications for carcinosarcoma, clear cell carcinoma, grade 1 endometrioid carcinoma, mucinous neoplasms, and low-grade serous carcinoma (monitoring/follow-up). For chronic lymphocytic leukemia/small lymphocytic lymphoma, added measurement at transformation or histologic progression (if applicable). Removed several prior initial diagnostic indications for pediatric ALL, Hodgkin lymphoma, MDS, and AML, and for some myeloproliferative neoplasms as noted in update history.

ALL of the following

Serum free light chain: For multiple myeloma, updated frequency of surveillance from 'as needed' to once per month; for systemic light chain amyloidosis, maintained indication for initial diagnostic workup.

ALL of the following

Tryptase: For systemic mastocytosis, removed indications for monitoring response to therapy and/or risk classification in the most recent revision; for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes, removed indication for initial diagnostic evaluation in prior versions where applicable.

ALL of the following

Other marker housekeeping changes: Multiple markers had ovarian cancer subgroup language expanded (added carcinosarcoma, clear cell carcinoma, grade 1 endometrioid carcinoma, mucinous neoplasms, low-grade serous carcinoma) to include monitoring/follow-up; several entries had the '(less common)' ovarian designation removed. References updated and several codes (e.g., 83521, 0404U, 0599U) were added on noted dates.

Selected updated coverage criteria for tumor markers

Selected updated coverage criteria for tumor markers — policy update history entries describing added/removed/revised covered indications; surface examples and applicability.

ALL of the following

08/01/2025: Added code 0599U effective 10/01/2025 (coding update).
10/30/2024 - 01/15/2025: Document updated with literature review resulting in multiple ovarian cancer marker expansions (added monitoring/follow-up indications for carcinosarcoma, clear cell carcinoma, grade 1 endometrioid carcinoma, mucinous neoplasms, low-grade serous carcinoma) and removal of '(less common)' designation for ovarian rows; B2M and CA marker updates for occult primary were added.

ALL of the following

04/15/2024: Reimbursement Information revised to organize serum tumor markers and indications by marker; additions and removals across many markers (see detailed marker-specific updates).

Reimbursable Markers, Indications, and Updates

Reimbursable markers and indications — designated serum tumor markers reimbursable for specific cancer-related indications with frequencies noted; focus on per-marker, per-diagnosis changes (added, removed, frequency revised).

ALL of the following

Alkaline phosphatase (ALP): Indication = Bone neoplasms: Workup; During treatment; Surveillance (quarterly measurement permitted unless otherwise specified).
Alkaline phosphatase (ALP): Indication = Systemic light chain amyloidosis: Initial diagnostic workup.

ALL of the following

Alpha fetoprotein (AFP): Indication = Hepatocellular carcinoma: Screening; Workup for confirmed HCC; Surveillance (every 3-6 months for 2 years; then every 6 months).
Alpha fetoprotein (AFP): Indication = Intrahepatic cholangiocarcinoma: Workup for isolated intrahepatic mass.

Procedure Codes and Surveillance Examples

Listed procedure codes (not exhaustive)mixed

83615
83789
83880
83950
83951
84075
84078
84080
84484
84702

1–10 of 14

1/2

Recently added codeHCPCSCovered

0599U

Newly added laboratory code (refer to policy effective 10/01/2025)

recently added codesCPT

83521	Added code referenced in policy update
0404U	Added code referenced in policy update

Surveillance frequency examples

CA 19-9 — resected ampullary cancerSurveillance every 3-6 months for 2 years, then every 6-12 months for up to 5 years as clinically indicated

Borderline ovarian epithelial tumors — AFP/beta-HCG/inhibin/CA-125Monitoring frequency revised to 'every visit if initially elevated'

Gestational trophoblastic neoplasia — beta-HCGDuring and post treatment: no more than weekly; follow-up/surveillance: no more than monthly for 12 months

Documentation, Claims, and Coding Actions for Providers

Documentation Required

Provider documentation and claims submission

Providers are responsible for submission of accurate documentation of services performed and must submit claims using valid HIPAA code sets. Claims should be coded according to industry-standard coding guidelines (e.g., AMA CPT, CMS HCPCS, ICD-10-CM/PCS, NDCs, DRG, CCI). Claims are subject to review against benefit coverage, provider contract terms, medical and clinical payment/coding policies, and code-edit software logic. Upon request, providers should furnish additional documentation to support medical necessity, diagnosis, procedures, and test ordering.

Submit claims with valid HIPAA-approved codes and adhere to standard coding manuals and CCI edits.
Retain and provide clinical documentation (history, test results, indications, ordering provider notes) when requested to support necessity and frequency of testing.
Claims may be denied or adjusted if coding is incomplete, inconsistent, or lacks supporting documentation.

Definitions and Marker Matrix Context

Plan document types

Certificates of Health Care BenefitsIncluded among plan documents that govern coverage

Benefit bookletsIncluded among plan documents that govern coverage

Summary Plan Descriptions (SPD)Included among plan documents that govern coverage

Other coverage documentsAdditional plan documents that may govern coverage decisions

Payer discretion

Discretionary authorityBlue Cross and Blue Shield of New Mexico may use reasonable discretion interpreting and applying this policy to services being delivered in a particular case

Policy Summary

PayerBlue Cross Blue Shield - New Mexico

PolicySerum Tumor Markers for Malignancies

Policy CodePolicy CPCPLABO37

Change TypeAdded codesexpanded/revised indications and monitoring frequencies

Effective DateOct 1, 2025

Next Review DateN/A

SourceLink

On This Page

Alpha fetoprotein (AFP): Indication = Ovarian cancers (including carcinosarcoma, clear cell carcinoma, grade 1 endometrioid carcinoma, mucinous neoplasms, low-grade serous carcinoma, borderline epithelial tumors): Initial workup; During primary chemotherapy; Monitoring/follow-up for complete response (as clinically indicated). For borderline epithelial tumors and other ovarian subtypes, monitoring frequency: every visit if initially elevated; for malignant germ cell tumors: surveillance schedule — no more than every 2 months for first 2 years, every 4 months in years 3-5, then annually after year 5.

ALL of the following

Beta human chorionic gonadotropin (beta-HCG): Indication = Gestational trophoblastic neoplasia: Initial workup; During and post treatment (no more than weekly); Follow-up/surveillance (no more than monthly for 12 months).
Beta human chorionic gonadotropin (beta-HCG): Indication = Occult primary: Additional workup for localized adenocarcinoma or carcinoma not otherwise specified; individuals <65 years with testes presenting with retroperitoneal mass.
Beta human chorionic gonadotropin (beta-HCG): Indication = Ovarian cancers (including borderline epithelial tumors and other specified subtypes): Initial workup; During primary chemotherapy; Monitoring/follow-up for complete response (as clinically indicated).
Beta human chorionic gonadotropin (beta-HCG): Indication = Testicular cancer non-seminoma and pure seminoma: Post-diagnostic workup; Risk classification; Post-treatment surveillance (no more than every 2 months as specified).

ALL of the following

Cancer antigen 19-9 (CA 19-9): Indication = Ampullary adenocarcinoma: Workup; Surveillance (every 3-6 months for 2 years, then every 6-12 months for up to 5 years as clinically indicated) for resected ampullary cancer stage I-III.
Cancer antigen 19-9 (CA 19-9): Indication = Appendiceal adenocarcinoma: Workup to establish baseline; Abnormal measurements should be trended.
Cancer antigen 19-9 (CA 19-9): Indication = Extrahepatic and intrahepatic cholangiocarcinoma, gallbladder cancer, pancreatic adenocarcinoma, small bowel adenocarcinoma: Workup to establish baseline; Monitoring; Post-operative surveillance timeframes as clinically indicated.

ALL of the following

Cancer antigen 125 (CA-125): Indication = Ovarian cancers (including carcinosarcoma, clear cell carcinoma, grade 1 endometrioid carcinoma, mucinous neoplasms, low-grade serous carcinoma, borderline epithelial tumors): Initial workup; During primary chemotherapy; Monitoring/follow-up for complete response (as clinically indicated). For borderline epithelial tumors: monitoring every visit if initially elevated.
Cancer antigen 125 (CA-125): Indication = Appendiceal adenocarcinoma: Workup to establish baseline; Monitoring; Surveillance (if initially elevated).
Cancer antigen 125 (CA-125): Indication = Lynch syndrome: Surveillance as clinically indicated; Occult primary additional workup for those with uterus and/or ovaries present.

ALL of the following

Carcinoembryonic antigen (CEA): Indication = Appendiceal adenocarcinoma: Workup to establish baseline; Monitoring; Post-treatment surveillance.
Carcinoembryonic antigen (CEA): Indication = Breast cancer (invasive): Monitoring metastatic disease.
Carcinoembryonic antigen (CEA): Indication = Colon cancer, rectal cancer: Workup to establish baseline; Monitoring; Surveillance (every 3-6 months for 2 years, then every 6 months for total of 5 years).
Carcinoembryonic antigen (CEA): Indication = Extrahepatic cholangiocarcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, medullary carcinoma: Workup and monitoring as clinically indicated.

Billing Rule

Coding update — new code 0599U

A coding update to the reimbursement table is effective 2025-10-01. Code 0599U has been added; providers should bill using 0599U when the service/test meets the described indication in the reimbursement table and documentation supports use of this specific code.

Add and bill code 0599U beginning 2025-10-01 where clinically appropriate per the updated reimbursement table.
Verify that claims use the correct code group (CPT/HCPCS) and modifiers where applicable to avoid denials.

Note

Monitoring frequency and indications — provider implications

Monitoring frequencies and indications for tumor markers and other monitored analytes have been revised. Providers must order and follow-up tests according to the updated indication and frequency guidance in the reimbursement table. For tests used for monitoring/follow-up, ensure baseline (initial) values are documented and that follow-up intervals recorded in the medical record match the policy-specified frequency (for example: changes described for AFP and beta-HCG monitoring frequencies).

Review the reimbursement table for marker-specific monitoring frequency (e.g., AFP, beta-HCG, CA 19-9) and document clinical rationale if deviating from stated frequencies.
Ensure ordering and result documentation clearly indicate whether the test is for initial workup, prognostic/therapy determination, monitoring during treatment, or surveillance/follow-up.
When a marker is listed as ‘monitoring/follow-up’ only if initially elevated, document the initial elevated result in the record to support subsequent monitoring claims.

Note

Refer to updated reimbursement table for codes, indications, and frequencies

Reimbursement information has been reorganized into a marker-by-marker table. Providers must reference the updated reimbursement table to determine which indications and monitoring frequencies are considered reimbursable and to identify the correct billing code to use (including the newly added 0599U).

Use the updated reimbursement table to confirm reimbursable indications and allowable monitoring frequencies before ordering or billing.
Cross-check the table to select the appropriate code for the service; use 0599U where indicated beginning 2025-10-01.
If clinical circumstances require testing outside of the table-specified indications/frequencies, document the medical necessity clearly in the medical record and submit supporting documentation with the claim.