Blue Cross Blue Shield - Tennessee Serum Biomarkers Coverage Update | OpenPayer
ModifiedBlue Cross Blue Shield - TennesseePolicy N/A
Serum Tumor Markers for Malignancies
Defines coverage indications, limitations, and CPT/HCPCS codes for serum tumor marker tests used in diagnosis, staging, monitoring, and surveillance of malignancies for BlueCross BlueShield of Tennessee members.
Key ActionVerify prior authorization and use updated procedure codes (including new CPT codes 0558U and 0559U) and ensure documentation supports the revised indication for each serum biomarker when ordering or billing.
Adjusted terminology from 'serum tumor markers' to 'serum biomarkers' to broaden definition.
Updated indications for multiple specific biomarkers (ALP, Beta-2 microglobulin, BNP/NT-proBNP, CA19-9, CA-125, CEA, HE4, Inhibin, serum free light chains) including additions, removals, and reorganization of indications.
Removed the entire Lactate dehydrogenase (LDH) section from the serum tumor biomarker table.
Added CPT codes 0558U and 0559U (effective 7/1/2025) and removed CPT code 83615.
>30CPT/HCPCS codes listed
~40+Procedure & proprietary codes
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Bibliographic references
>=2New CPT codes added
1Biomarker sections removed
multipleTable indication updates
Coverage Criteria for Serum Biomarkers
Coverage Criteria — Included Serum Biomarkers
Covered indications (selected examples) — measurement of specified serum biomarkers meets coverage criteria for the listed indications when used for diagnostic workup, monitoring, surveillance, or follow-up as noted. Except where otherwise specified, quarterly measurement is permitted for follow-up, monitoring, and/or surveillance.
ANY of the following
Alkaline phosphatase (ALP): meets coverage criteria for workup of bone neoplasms and for workup of melanoma (uveal).
Alpha fetoprotein (AFP): meets coverage criteria for initial diagnostic workup of systemic light chain amyloidosis; workup for intrahepatic cholangiocarcinoma for isolated intrahepatic mass; additional workup for occult primary (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, and monitoring/follow-up for complete response as clinically indicated; multiple ovarian cancer subtypes for monitoring/follow-up (carcinosarcoma, clear cell, grade 1 endometrioid, mucinous neoplasms, low-grade serous); ovarian borderline and germ cell tumor surveillance per specified frequencies; testicular cancer (nonseminoma and pure seminoma) for workup, risk classification, and surveillance per specified frequencies.
Beta-2 microglobulin (B2M): meets coverage criteria for workup and prognostic/therapy determination in chronic lymphocytic leukemia/small lymphocytic lymphoma; for multiple myeloma initial diagnostic workup and follow-up/surveillance as needed for solitary plasmacytoma; for systemic light chain amyloidosis initial diagnostic workup; for Waldenström macroglobulinemia/lymphoplasmacytic lymphoma workup; Castleman disease — workup (added).
BNP or NT-proBNP: meets coverage criteria for indicated cardiac-related assessments and specific hematologic indications per policy (note: systemic light chain amyloidosis indication moved to Troponin T section during revision).
Calcitonin (CALCA): meets coverage criteria for workup of adenocarcinoma and anaplastic/undifferentiated epithelial tumors; medullary thyroid carcinoma — additional workup, post-surgical evaluation, monitoring, and surveillance (2–3 months postoperative, then every 6–12 months); multiple endocrine neoplasia type 2 — clinical evaluation at diagnosis; occult primary — workup.
Cancer antigen 15-3 and 27.29 (CA 15-3 and 27.29): meets coverage criteria for monitoring metastatic breast cancer.
Cancer antigen 19-9 (CA 19-9): meets coverage criteria for workup and baseline/monitoring/surveillance for ampullary adenocarcinoma, appendiceal adenocarcinoma (baseline), extrahepatic cholangiocarcinoma (baseline/monitoring), gallbladder cancer (baseline/monitoring/post-resection surveillance as clinically indicated), intrahepatic cholangiocarcinoma (baseline/monitoring), pancreatic adenocarcinoma (baseline/monitoring/post-op and post-adjuvant surveillance per schedule), and select occult primary indications to establish baseline.
Cancer antigen 125 (CA-125): meets coverage criteria for workup and baseline in appendiceal adenocarcinoma; initial evaluation/workup for occult primary when uterus and/or ovaries present; ovarian/fallopian tube/primary peritoneal cancer — initial workup, during primary chemotherapy, monitoring/follow-up for complete response as clinically indicated; uterine neoplasms — additional workup/surveillance.
Carcinoembryonic antigen (CEA): meets coverage criteria for baseline/monitoring/post-treatment surveillance in appendiceal adenocarcinoma; monitoring metastatic breast cancer; colon cancer — baseline/monitoring and surveillance schedule (every 3–6 months for 2 years, then every 6 months for total of 5 years); extrahepatic cholangiocarcinoma baseline/monitoring; intrahepatic cholangiocarcinoma baseline; medullary carcinoma — diagnosis and additional workup, monitoring, and post-surgical surveillance (2–3 months postoperative, then every 6–12 months); occult primary — workup for adenocarcinoma or carcinoma not otherwise specified.
Human epididymis protein 4 (HE4): meets coverage criteria for ovarian/fallopian tube/primary peritoneal cancer — initial workup, during primary chemotherapy, and monitoring/follow-up for complete response as clinically indicated; monitoring/follow-up indications for various less common ovarian cancer subtypes and borderline/malignant germ cell/sex cord stromal tumors per specified frequencies and indications.
Inhibin (INHA): meets coverage criteria for occult primary (additional workup for adenocarcinoma or carcinoma not otherwise specified) and for ovarian/fallopian tube/primary peritoneal cancer — initial workup, during primary chemotherapy, monitoring/follow-up for complete response as clinically indicated; applicable monitoring for specified ovarian subtypes and surveillance schedules.
Serum free light chains (sFLC): meets coverage criteria for Castleman disease workup; multiple myeloma — initial diagnostic workup, follow-up, and surveillance (up to once per month); systemic light chain amyloidosis — initial diagnostic workup.
Troponin T: meets coverage criteria for initial diagnostic workup of systemic light chain amyloidosis.
Tryptase: meets coverage criteria for initial diagnosis of systemic mastocytosis.
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Coverage Criteria — Revisions
Revised biomarker coverage and indications — coverage and indications updated for specific biomarkers; changes are additive/clarifying to prior table entries.
ANY of the following
Adjusted terminology: 'serum tumor markers' broadened to 'serum biomarkers' to reflect some serum-related markers more accurately described as biomarkers rather than tumor markers.
ALP: removed 'during treatment, surveillance' from indications for bone neoplasms; added 'Melanoma (uveal)' as an indication for workup.
Beta-2 microglobulin: Castleman disease indication moved/clarified as a separate entry for workup.
Chorionic gonadotropin beta polypeptide (CGB3): renamed from Beta‑human chorionic gonadotropin (beta‑hCG); modified occult primary language to 'mediastinum or' under occult primary designation.
Coverage Criteria — Marker-specific Examples
Many tumor markers are covered for specified cancer types and clinical scenarios — marker-by-marker indications consolidated below (examples).
ANY of the following
AFP: see Covered indications; multiple testicular and ovarian tumor subtypes and surveillance schedules outlined in the policy.
CA‑125 and HE4: used for ovarian/fallopian tube/primary peritoneal cancer initial workup, monitoring during chemotherapy, and monitoring/follow-up for complete response as clinically indicated; applicable to several less common ovarian histologies and surveillance schedules.
CA 19‑9: baseline and monitoring for biliary, pancreatic, ampullary, gallbladder, and intrahepatic cholangiocarcinoma; post-operative and surveillance schedules where specified.
CEA: baseline, monitoring, and surveillance for colorectal cancer and other indicated GI and medullary thyroid malignancies; monitoring metastatic breast cancer.
Coverage Criteria — Use and Operational Notes
Diagnostic, prognostic, and monitoring uses of serum tumor markers and related assays across oncology, hematology, and cardiology contexts are supported only when aligned with the specific indications listed in this policy and when clinical documentation supports their medical necessity.
ALL of the following
Use of biomarkers for cancer screening or for indications not specifically listed in this policy does not meet coverage criteria (see Not Medically Necessary/Not Covered below).
When a biomarker is performed for monitoring or surveillance, frequency should follow the schedules specified in this policy (e.g., malignant germ cell tumor surveillance: no more than every 2 months for first 2 years, every 4 months in years 3–5, then annually after year 5; colon cancer surveillance: every 3–6 months for 2 years, then every 6 months to complete 5 years), or be clinically justified in documentation.
Laboratory CPT codes and analyte-specific codes listed in the policy (e.g., 83521, 83789, 83880, 83950, 84484, 84702–84704, 86300–86305, 86316, 86336, 0558U, 0559U) should be used as applicable for billing; proprietary multi‑analyte tests are addressed separately (e.g., 0003U Overa™).
Not Medically Necessary / Not Covered
Not medically necessary / Not covered
ALL of the following
Analysis of proteomic patterns in serum for the screening and detection of cancer does not meet coverage criteria.
For all other cancer indications not discussed above, use of the listed biomarkers (alone or in a panel of serum tumor markers) does not meet coverage criteria.
All other serum tumor markers not addressed above (alone or in a panel of serum tumor markers) do not meet coverage criteria.
Lactate dehydrogenase (LDH) is explicitly excluded and does not meet coverage criteria as a covered serum biomarker under this policy.
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Covered Indications and Marker-Specific Uses
Workup, initial evaluation, monitoring/follow-up, and surveillance (updated per biomarker rows)
Workup, initial evaluation, monitoring/follow-up, and surveillance are permitted for specific cancers according to the updated biomarker table entries and marker-specific recommendations.
ALP and bone-related indications: ALP: covered for workup of bone neoplasms and workup of melanoma (uveal) as added in the revisions. Removed 'during treatment, surveillance' for ALP in bone neoplasms.
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Ovarian and uterine cancer workup and monitoring: CA-125, HE4, inhibin, and AFP: covered for initial workup, during primary chemotherapy, and monitoring/follow-up for complete response as clinically indicated; uterine neoplasms and occult primary indications expanded to include additional workup/surveillance.Surveillance intervals marker-dependent; see policy (quarterly permitted unless specified)
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Procedure and Proprietary Test Codes
Listed procedure codes (selection)CPT
81479
Unlisted molecular pathology procedure.
81599
Unlisted multianalyte assay with algorithmic analysis.
82105
Alpha-fetoprotein (AFP); serum.
82107
Alpha-fetoprotein (AFP); AFP-L3 fraction isoform and total AFP (including ratio).
82232
Beta-2 microglobulin.
82308
Calcitonin.
82378
Carcinoembryonic antigen (CEA).
83520
Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
Mass spectrometry and tandem mass spectrometry (eg, MS, MS/MS, MALDI, MS- TOF, QTOF), non-drug analyte(s) not elsewhere specified, qualitative or quantitative, each specimen.
83880
Natriuretic peptide.
83950
Oncoprotein; HER-2/neu.
83951
Oncoprotein; des-gamma-carboxy-prothrombin (DCP).
84075
Phosphatase, alkaline.
84078
Phosphatase, alkaline; heat stable (total not included).
84080
Phosphatase, alkaline; isoenzymes.
84484
Troponin, quantitative.
84702
Gonadotropin, chorionic (hCG); quantitative.
1–10 of 19
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Proprietary and other specific assay codesCPT
0003U
Oncology (ovarian) biochemical assays of five proteins with algorithm reported as a likelihood score (OVA1 Next Generation).
0092U
Oncology (lung), three protein biomarkers with algorithm reported as risk score (REVEAL Lung Nodule Characterization).
0163U
Oncology (colorectal) screening, ELISA of 3 plasma/serum proteins with proprietary algorithm (BeScreened - CRC).
0404U
Oncology (breast), semiquantitative thymidine kinase activity by immunoassay, reported as risk of disease progression (Divitum Tka).
G0327
Colorectal cancer screening; blood-based biomarker.
Procedure and Proprietary Test Codes (selected)CPT
Mass spectrometry and tandem mass spectrometry (eg, MS, MS/MS, MALDI, MS- TOF, QTOF), non-drug analyte(s) not elsewhere specified, qualitative or quantitative, each specimen.
83880
Natriuretic peptide.
83950
Oncoprotein; HER-2/neu.
83951
Oncoprotein; des-gamma-carboxy-prothrombin (DCP).
84075
Phosphatase, alkaline.
84078
Phosphatase, alkaline; heat stable (total not included).
84080
Phosphatase, alkaline; isoenzymes.
84484
Troponin, quantitative.
84702
Gonadotropin, chorionic (hCG); quantitative.
1–10 of 20
1/2
Proprietary and screening test codesCPT
0092U
Oncology (lung), three protein biomarkers, immunoassay using magnetic nanosensor technology, algorithm reported as risk score for likelihood of malignancy (Proprietary test: REVEAL Lung Nodule Characterization).
0163U
Oncology (colorectal) screening, biochemical ELISA of 3 plasma or serum proteins with demographic data using a proprietary algorithm reported as likelihood of CRC or advanced adenomas (Proprietary test: BeScreened™ -CRC).
0404U
Oncology (breast), semiquantitative measurement of thymidine kinase activity by immunoassay, serum, results reported as risk of disease progression (Proprietary test: Divitum®Tka).
G0327
Colorectal cancer screening; blood-based biomarker.
Updated CPT codesCPT
0558U
CPT code added (document lists as added)
0559U
CPT code added (document lists as added)
83615
CPT code removed (document lists as removed)
Surveillance frequency examples
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.
Testicular cancer — nonseminoma (surveillance)Surveillance no more than every 2 months.
Testicular cancer — pure seminoma (post-treatment surveillance)Post-treatment surveillance no more than every 2 months.
Ovarian borderline epithelial tumors (monitoring)Monitoring/follow-up at every visit if initially elevated.
Numeric threshold note
Testing Frequency and Surveillance Intervals
Marker-specific frequency examples
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.
CA 19-9 and other markers after resection (pancreatic adenocarcinoma)Post‑operative/post‑adjuvant surveillance every 3–6 months for 2 years, then every 6–12 months as clinically indicated.
Serum free light chains (multiple myeloma)Up to once per month for monitoring in multiple myeloma (frequency varies by indication).
Designated serum biomarkers — routine interval
Designated serum biomarkers (general rule)Quarterly measurement (every 3 months) is permitted for follow‑up, monitoring, and/or surveillance unless otherwise specified in the policy.
Exceptions
Provider Actions, Billing, and Documentation
Billing Rule
Procedure codes and billing guidance
Use the listed CPT/HCPCS procedure codes on claims. Submit the appropriate code(s) that correspond to the tests performed and the proprietary assays referenced in the policy. Procedure codes included in the Medical Policy are provided as a general reference and may not be all-inclusive; providers should verify current code sets and payer-specific billing guidance prior to submission.
Procedure codes listed in policy are for general reference and may not be exhaustive.
Verify payer-specific prior authorization requirements for listed laboratory and proprietary oncology panel codes before ordering.
Effective 07/01/2025: CPT codes 0558U and 0559U were added; CPT 83615 was removed. Ensure prior authorization and billing reflect these updates.
Denial Risk
Ordering and Prior Authorization Requirements
Documentation Required
Government policy supersedes this policy when conflicting
When Medicare or Medicaid (LCD/NCD or state Medicaid) policy conflicts with this policy for a member, follow the applicable government coverage determination.
Consult the Medicare Coverage Database or the applicable state Medicaid website for the controlling policy.
Government determinations will be used to adjudicate coverage for impacted members.
Note
Ordering requirements note — no provider-type restrictions in excerpt
No specific ordering provider restrictions are stated in this excerpt; follow standard ordering practices and payer requirements.
The policy excerpt does not impose practitioner-type ordering limitations.
Verify any payer-specific ordering provider requirements separately.
Not Covered / Exclusions
Analysis of proteomic patterns in serum for screening and detection of cancer does not meet coverage criteria. This statement reinforces that proteomic pattern assays for cancer screening or detection lack sufficient published evidence to support coverage under this policy.
No explicit additional 'not covered' tests are listed in this excerpt beyond the general exclusions already stated in the policy. Procedure codes included in the document are provided as a reference and may not be all-inclusive; coverage determinations depend on the specific test and indication billed.
LDH has been removed from the serum biomarker table and is not a covered tumor biomarker under this policy. This operational change means LDH should not be used or billed as a serum tumor marker for covered oncology indications within the scope of this policy.
Background and Scope
Circulating tumor biomarkers are substances detected in body fluids that are produced by a tumor or in response to a tumor and can assist with detection, diagnosis, staging, and management because levels are often elevated in individuals with tumors. The policy aligns with current guideline sources (for example, the NCCN Biomarkers Compendium) and describes biomarker use across clinical scenarios including diagnostic workup, baseline assessment, monitoring of therapy response, and surveillance.
Definitions
Circulating tumor biomarkers
DefinitionCirculating tumor biomarkers are substances detected in blood, urine, or other body fluids that are produced by a tumor or in response to a tumor.
Clinical useUsed to help detect, diagnose, stage, and manage some types of cancer because levels are typically elevated in individuals harboring a tumor.
Policy scopeThis laboratory policy addresses tumor markers which may be measured in an individual's serum (term broadened to 'serum biomarkers' in revisions).
Laboratory‑developed test (LDT)
DefinitionLaboratory‑developed test (LDT): a test developed and validated by a laboratory and regulated by CMS under CLIA as a high‑complexity test; not FDA‑approved/cleared.
Regulatory contextLDTs are regulated under the Clinical Laboratory Improvement Amendments (CLIA) and are not approved or cleared by the U.S. Food and Drug Administration for clinical use.
Policy Revision History and Material Changes
2025-06-04Terminology and indications updateLatest
Policy terminology was broadened from 'Serum Tumor Markers' to 'Serum Biomarkers' and multiple biomarker indications and table entries were revised (ALP, B2M, CGB3/beta-hCG, CA19-9, CA-125, CEA, HE4 and others).
2025-06-04LDH removal
The Lactate dehydrogenase (LDH) section was removed from the serum biomarker table because LDH was deemed too broad for serum tumor biomarker designation.
Key ActionVerify prior authorization and use updated procedure codes (including new CPT codes 0558U and 0559U) and ensure documentation supports the revised indication for each serum biomarker when ordering or billing.
BNP/NT‑proBNP: systemic light chain amyloidosis initial diagnostic workup indication removed and moved to Troponin T section.
CA 19‑9, CA‑125, CEA, HE4, Inhibin, and Serum free light chains: updated indications and added monitoring/follow-up or initial workup language, consolidation of ovarian cancer subtypes, and added Castleman disease to sFLC.
LDH: removed entirely from the table; LDH is excluded as a covered serum biomarker.
Calcitonin: diagnosis and surveillance for medullary thyroid carcinoma and related indications.
Serum free light chains and immunoglobulin free light chains (CPT 83521): diagnostic and monitoring role in multiple myeloma, systemic light chain amyloidosis, Waldenström, and Castleman disease; testing frequency guidance included.
Troponin T: diagnostic workup for systemic light chain amyloidosis.
paragraphs([]),
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Germ cell and testicular tumor surveillance:
AFP (and other germ cell markers where applicable): surveillance for malignant germ cell tumors no more than every 2 months for the first 2 years, every 4 months in years 3-5, then annually after year 5; testicular cancer surveillance guidance for nonseminoma and seminoma as specified.
No more than every 2 months for first 2 years (germ cell tumors); other timing as specified in policy
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Hepatobiliary and pancreatic cancer monitoring: CA 19-9: baseline workup and monitoring for ampullary, appendiceal, extrahepatic/intrahepatic cholangiocarcinoma, gallbladder, and pancreatic adenocarcinoma; post-resection surveillance example: every 3-6 months for 2 years then every 6-12 months as clinically indicated.Every 3-6 months for 2 years then every 6-12 months as clinically indicated (post-resection example)
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Plasma cell disorders and Castleman disease: Serum free light chains and beta-2 microglobulin: indicated for workup of Castleman disease; multiple myeloma initial diagnostic workup and follow-up/surveillance (up to once per month).Up to once per month for follow-up in multiple myeloma
chunk 13
Marker-by-marker coverage examples and scenarios
Marker-by-marker examples and typical clinical scenarios for diagnostic workup, baseline establishment, monitoring, surveillance, and post-treatment follow-up are listed below.
AFP (examples): Initial diagnostic workup for systemic light chain amyloidosis; workup for intrahepatic cholangiocarcinoma isolated mass; ovarian cancer initial workup and monitoring during therapy and follow-up; surveillance schedules for malignant germ cell tumors and testicular cancers as specified.Marker-specific surveillance intervals (see policy)
chunk 3
CA-125 and HE4 (examples): CA-125 and HE4: used for initial evaluation/workup and monitoring of ovarian/fallopian tube/primary peritoneal cancers, uterine neoplasm additional workup/surveillance, and borderline epithelial tumor monitoring (every visit if initially elevated).Follow marker-specific intervals; quarterly permitted unless otherwise specified
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CA 19-9 and CEA (examples): CA 19-9: baseline and monitoring for pancreatic, biliary, ampullary, and gallbladder cancers; CEA: baseline, monitoring, and surveillance for colon cancer and baseline/monitoring for appendiceal and extrahepatic cholangiocarcinoma.CA19-9 post-resection surveillance every 3-6 months for 2 years then every 6-12 months as clinically indicated; CEA surveillance every 3-6 months for 2 years then every 6 months up to 5 years.
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Calcitonin and medullary carcinoma: Calcitonin: additional workup, post-surgical evaluation, monitoring and surveillance for medullary carcinoma (2-3 months postoperative, then every 6-12 months).Postoperative surveillance: 2-3 months then every 6-12 months
chunk 5
Serum free light chains and hematologic uses: SFL: Castleman disease workup; multiple myeloma initial diagnostic workup and follow-up/surveillance (up to once per month); systemic light chain amyloidosis initial diagnostic workup.Up to once per month for multiple myeloma surveillance
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Use across oncology, hematology, cardiology (examples & references)
Examples of how these biomarkers are applied across oncology, hematology, and cardiology contexts, with supporting references cited in the policy.
Oncology applications: Markers (AFP, CA-125, CA 19-9, CEA, HE4, inhibin, CA15-3/27.29, etc.) used for tumor-specific workup, baseline assessment, monitoring response to therapy, and post-treatment surveillance according to the policy and guideline references.
See bibliographic references in policy for evidence support
Hematology applications: Serum free light chains, beta-2 microglobulin, and related assays used for diagnosis, monitoring, and prognostic assessment in multiple myeloma, Waldenström macroglobulinemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Castleman disease.
chunk 31; chunk 13
Cardiology/amyloidosis applications: Troponin T and selected natriuretic peptides are used for initial diagnostic workup and cardiac involvement assessment in systemic light chain amyloidosis where indicated.
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Numeric thresholdsNo numeric test thresholds are provided in this section of the policy.
Frequency guidanceQuarterly measurement is permitted for designated serum biomarkers for follow-up/monitoring unless otherwise specified (see frequency-specific rows).
Clinical judgmentWhen specific numeric cutoffs are required for interpretation, follow assay-specific reference ranges and clinical guidelines; such numeric thresholds are not listed here.
Specific biomarkers or indications may have different surveillance intervals noted in their table rows (e.g., germ cell tumors, ovarian subtypes).
DocumentationOrders and documentation should reference the biomarker-specific indication and frequency consistent with the policy.
Frequency placeholder
Frequency placeholder 1No specific text excerpt provided for this placeholder frequency item in the source document.
ActionFollow marker-specific rows and general quarterly rule where applicable.
NoteIf frequency is clinically critical, consult the full policy table for the biomarker-specific interval.
Frequency placeholder
Frequency placeholder 2No specific text excerpt provided for this placeholder frequency item in the source document.
ActionRefer to per-biomarker coverage rows in the policy for specified intervals.
If unclearContact medical policy or utilization management for authorization guidance.
Denial risk and documentation requirements
Testing performed outside the policy's specified and updated indications may be denied. Claims should be supported by clinical documentation that justifies the use of the specific serum biomarker for the indicated purpose (e.g., initial workup, monitoring/follow-up, surveillance). Providers should be aware that removal of certain tests (for example LDH) from the serum biomarker table indicates they are out-of-scope for coverage under this policy and may increase denial risk if billed for those indications.
Tests performed for cancer indications not discussed in the policy do NOT meet coverage criteria and are at risk for claim denial.
All claims must include documentation supporting the precise updated indication used for each serum biomarker (workup, monitoring/follow-up, initial evaluation).
Quarterly measurement is permitted for follow-up/monitoring/surveillance only where specified in the policy.
Documentation Required
Regulatory and documentation note
Documentation must support the medical necessity and the specific indication for each serum biomarker ordered. Government (Medicare/Medicaid) coverage rules supersede this policy where conflicts exist. Laboratory-developed tests (LDTs) and proprietary panels should be clearly identified in the record, including the test name, performing laboratory, and algorithm or components when applicable.
Include the reason for testing (e.g., workup, initial evaluation, monitoring/follow-up) in the medical record.
For proprietary tests (e.g., Overa™, REVEAL, BeScreened™, Divitum®Tka), document the test name and laboratory.
Verify and follow any payer-specific prior authorization processes before ordering tests that require it.
Documentation Required
Ordering must align with updated indications per biomarker
Ensure each order aligns with the policy's updated biomarker indications (workup, initial evaluation, monitoring/follow-up, surveillance) as specified in the revised table entries.
Order tests only when the clinical indication matches the biomarker-specific coverage in the policy.
No specific practitioner-type ordering restrictions are provided in this excerpt.
Clinical implicationWhen using LDTs, follow CLIA requirements and document the specific assay used when billing or seeking prior authorization.
Proprietary multi‑analyte tests
DefinitionProprietary test: commercially developed multi‑analyte biomarker panels reported with an algorithm‑derived risk or likelihood score.
ExamplesOvera™ (OVA1 Next Generation), REVEAL Lung Nodule Characterization, BeScreened™ - CRC, Divitum®Tka (see CPT codes 0003U, 0092U, 0163U, 0404U).
Billing noteProprietary panel codes and descriptions are listed in the policy and should be used for claims; verify payer prior authorization requirements.
Terminology change — 'serum biomarkers'
Terminology updatePolicy terminology was changed from 'serum tumor markers' to 'serum biomarkers' to broaden the definition and include markers not strictly tumor markers.
Table title changeTitle in the biomarker table was changed from 'Serum Tumor Markers' to 'Serum Biomarkers.'
ReasonSome serum‑related markers are more accurately described as biomarkers rather than tumor markers; revisions reflect guidance from NCCN Biomarkers Compendium.
Coding update
CPT codes 0558U and 0559U were added (effective 2025-07-01) and CPT code 83615 was removed to align coding with updated tests.
This policy defines coverage indications, limitations, and applicable CPT/HCPCS procedure codes for serum tumor marker tests used in diagnosis, staging, monitoring, and surveillance for BlueCross BlueShield of Tennessee members. Specific markers (for example, AFP, CA-125, CA 19-9, CEA, HE4, inhibin, serum free light chains, troponin T) are listed with permitted clinical scenarios and, where specified, surveillance frequencies. Providers must use the listed procedure codes when submitting claims and verify payer-specific prior authorization requirements for proprietary or multi-analyte assays. Note that coding updates were made (CPT codes 0558U and 0559U were added and CPT 83615 was removed) and that LDH was removed from the biomarker table and is not covered as a tumor biomarker under this policy.