CurrentBlue Cross Blue Shield - South DakotaPolicy N/A

Tumor Markers in the Management of Malignancies — Coverage Criteria

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This policy governs coverage and medical necessity criteria for laboratory tumor marker tests used in evaluation, monitoring, and management of various malignancies for Blue Cross Blue Shield - South Dakota members.

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CurrentBlue Cross Blue Shield - South DakotaPolicy N/A

Tumor Markers in the Management of Malignancies — Coverage Criteria

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Policy Summary

PayerBlue Cross Blue Shield - South Dakota

PolicyTumor Markers in the Management of Malignancies — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateDec 1, 2020

Last ReviewFeb 1, 2025

Next Review DateN/A

Key ActionVerify member benefits and document indication, tumor marker tested, rationale, and how results will change management.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Feb 16, 2025Evidence updated

MultipleMarkers addressed

>=1CPT codes listed

No established cutoffHE4 cutoff

529Rustin trial patients

Coverage and Medical Necessity Criteria

Medically necessary tumor marker indications

Measurement of the following tumor markers may be considered medically necessary in the evaluation and management of cancer when used for the listed indications:

CA 19-9 indications: CA 19-9: Ampullary adenocarcinoma; Biliary tract cancers including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer; to aid detection of cholangiocarcinoma in patients with primary sclerosing cholangitis; gastric cancer; mucinous appendiceal carcinoma; ovarian cancer; pancreatic cancer; pseudomyxoma peritonei/mucinous carcinoma of the ovary.

CA 15-3 / CA 27.29 indications: CA 15-3 (also known as CA 27.29): Following the course of treatment in individuals diagnosed with breast cancer, especially advanced/metastatic breast cancer. An increasing CA 15-3 (CA 27.29) may suggest treatment failure.

CA-125 indications: CA-125: Endometrial cancer; evaluation of pelvic/ovarian mass suspected to be malignant; mucinous appendiceal adenocarcinoma; ovarian cancer including pre-treatment evaluation to inform surgical vs adjuvant/neoadjuvant chemotherapy decisions; occult primary presentations in individuals with a uterus/ovaries present (chest with multiple nodules or pleural effusion; peritoneal/ascites; retroperitoneal mass; inguinal nodes; possible ovarian primary); primary peritoneal cancer; uterine neoplasms.

CEA indications: Carcinoembryonic antigen (CEA): Ampullary adenocarcinoma; biliary tract cancers (intrahepatic and extrahepatic cholangiocarcinoma, gallbladder); colorectal cancer; lung cancer; medullary thyroid carcinoma; metastatic breast cancer; mucinous appendiceal carcinoma; occult primary (including hepatocellular carcinoma and medullary thyroid carcinoma); ovarian cancer; pancreatic cyst fluid CEA for distinguishing mucinous from non-mucinous malignant pancreatic cysts; prostate cancer; pseudomyxoma peritonei/mucinous carcinoma of the ovary.

Chromogranin A (CgA) indications: Chromogranin A (CgA): Neuroendocrine tumors; non-small cell lung cancer; occult primary presentations (medullary thyroid carcinoma, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer); prostate cancer; small cell lung cancer.

5-HIAA indications: 5-HIAA (24-hour urine): Neuroendocrine tumors.

Investigational / Not covered tumor markers

The following markers and situations are considered investigational (not medically necessary) because evidence is insufficient to demonstrate improved net health outcomes:

Investigational markers list: When the medically necessary criteria above are not met; A2-PAG; BCM; CA 72-4; CA-50; CA-242; CA-195; CA-549; CAM 17-1; CAM-26; CAM-29; CA-SCC; CAR-3; DMSA; Du-PAN-2; EPCA-2; Human epididymis protein 4 (HE4); MCA; NSE; P-LAP; PNA-ELLA; P53; SLEX; SLX; SPAN-1; TPA; TPS; TAG-12; TAG 72; TAG-72-3; TNF-alpha; TATI.

Policy explicitly lists HE4 among investigational markers in this list unless specific medically necessary criteria are met.

General investigational condition: Tumor marker tests not meeting the specific medically necessary indications listed above are considered investigational/not covered because evidence is insufficient to show they change net health outcomes.

General medical necessity criteria

Coverage stance and required evidentiary justification

General coverage logic: Coverage for tumor marker testing is limited to uses where clinical utility is demonstrated and where results lead to management changes that improve health outcomes. Tests lacking clear placement in the clinical pathway, without established decision thresholds, or without evidence of impact on outcomes are not supported.

Evidence examples include randomized trial data and prospective studies showing improved survival or management changes leading to better outcomes.

CA-125 surveillance

Specific evidence relevant to CA-125 surveillance in ovarian cancer

CA-125 surveillance: Routine CA-125 surveillance in patients in complete remission following first-line platinum-based chemotherapy does not improve overall survival based on randomized trial evidence (Rustin et al., 2010; 529 women). Coverage for routine surveillance testing intended solely to detect recurrence earlier without demonstrated outcome benefit is restricted.

Rustin trial: CA-125 >2x upper limit of normal triggered randomization to early vs delayed chemotherapy; no OS benefit at median 56.9 months follow-up.

HE4 monitoring/prognostic criteria

Evidence and limitations for HE4 use in ovarian cancer

HE4 monitoring and prognostic use: Observational studies and FDA 510(k) submission data indicate HE4 may perform similarly to CA-125 for detecting progression and may be associated with prediction of platinum resistance and recurrence in some cohorts. however, no prospective randomized studies demonstrate that HE4-guided management improves health outcomes; study cutoffs and thresholds vary across reports.

Examples: FDA studies used 25% and 14% rise cutoffs; meta-analysis reported preoperative sensitivity ~80% and variable specificity; observational studies report varied cutoffs (e.g., 70 pmol/L, 199.20 pmol/L) and timing (after third cycle). Clinical use should be cautious and generally investigational unless intended result will change management with proven benefit.

Evidence and Coverage Implications

Summary of evidence and implications for coverage decisions

Evidence requirements for clinical utility: Clinical utility requires direct evidence from studies comparing health outcomes with and without the test (ideally randomized controlled trials). Such direct evidence was not identified for HE4; for CA‑125, randomized evidence showed no overall survival benefit for early treatment based solely on CA‑125 rise. Therefore, routine use of HE4 for monitoring, recurrence detection, or as the sole basis for management decisions is not supported absent evidence that testing leads to improved health outcomes.

Policy bases restrictions on absence of RCTs for HE4 and negative randomized CA-125 trial (Rustin et al.).

Measurement of tumor markers listed as investigational in this policy (including but not limited to HE4 and the markers enumerated in the investigational list) is considered investigational and not covered when the specific criteria for medically necessary testing are not met. The policy states these markers are investigational because the evidence is insufficient to demonstrate improved net health outcomes when used outside of the medically necessary indications.

Routine use of tumor marker testing for diagnosis, prognosis, or monitoring is not supported when clinical utility has not been demonstrated, when the test’s placement in the clinical pathway is unclear, or when thresholds for decision making are lacking. Coverage is limited to indications where results are expected to change management in ways that improve health outcomes.

Human epididymis protein 4 (HE4) should not be used as the sole basis for clinical management decisions. The policy notes there is no direct trial evidence that HE4-guided management improves health outcomes, and therefore HE4 results alone should not dictate major treatment changes without corroborating clinical, imaging, or other biomarker information.

Some portions of the source material do not include explicit clinical coverage exclusion statements; instead they provide coding and billing guidance. Providers must follow the listed CPT/HCPCS and other coding instructions when reporting tumor marker assays.

HE4 and the other markers identified in the investigational list are specifically designated as investigational (not medically necessary) in this policy unless the medically necessary criteria described elsewhere in the policy are met. This designation reflects the assessment that current evidence is insufficient to demonstrate that testing with these markers improves net health outcomes.

Serial measurement of CA‑125 for routine surveillance in ovarian cancer patients in complete remission is addressed by randomized trial evidence (Rustin et al. 2010). In that trial of 529 women, initiating earlier chemotherapy based solely on CA‑125 rise (>2× upper limit of normal) did not improve overall survival, and routine CA‑125 surveillance intended only to trigger earlier chemotherapy is therefore not supported.

Routine monitoring with HE4 to detect ovarian cancer recurrence or to guide earlier treatment is not supported by direct evidence of patient benefit. Observational and FDA 510(k) studies compare HE4 with CA‑125 and show variable performance and no established monitoring cutoff; however, no prospective controlled studies demonstrate that HE4‑directed management improves health outcomes.

There are sections of the document where explicit 'not medically necessary' statements are not provided; in these areas the document focuses on procedural coding and billing guidance. Providers should consult the policy’s investigational and not‑medically‑necessary sections for coverage determinations rather than relying solely on the coding tables.

Billing and Code Reporting

See Codes tablemixed

No codes listed

Listed CPT Codes for tumor marker assaysCPTCovered

82378	Carcinoembryonic antigen (CEA)
83497	Hydroxyindolacetic acid 5-HIAA
86300	Immunoassay for tumor antigen, quantitative; CA 15-3 (27.29)
86301	Immunoassay for tumor antigen, quantitative; CA 19-9
86304	Immunoassay for tumor antigen, quantitative; CA 125
86305	Human epididymis protein (HE4)
86316	Immunoassay for tumor antigen; other antigen, quantitative (e.g., CA 50, 72- 4, 549), each (This code may be used for Chromogranin A)
84999	Unlisted chemistry procedure

HE4 monitoring note

Monitoring contextSerial HE4 testing should be performed in conjunction with other clinical methods (imaging, clinical assessment); HE4 is not intended to be the sole basis for management decisions.

Regulatory noteFDA-cleared HE4 assays indicate serial testing is an adjunct to other monitoring methods rather than a standalone decision tool.

Evidence limitationNo prospective randomized trials demonstrate that HE4-guided management improves health outcomes; use should be contextualized with established clinical pathways.

HE4 cutoff

Summary statementNo established universal cutoff for HE4 exists; cutoffs varied across studies and FDA pivotal documents note lack of a clinically accepted monitoring cutoff.

Provider Responsibilities, Authorization & Documentation

Prior Authorization

Prior approval not applicable

Prior approval is not required for tumor marker testing under this policy.

Prior Authorization

Prior authorization may be required for surveillance testing

Prior authorization may be requested or required when testing is intended for routine surveillance or monitoring (for example, surveillance intended solely to detect recurrence earlier without demonstrated outcome benefit).

Policy notes CA-125 surveillance trial (Rustin et al. 2010) demonstrating no overall survival benefit for early treatment triggered by marker rise.

Prior Authorization

Document clinical intent and expected management changes for HE4

Background and Scope

Tumor markers are substances (for example proteins, antigens, or hormones) produced by tumors or by the body in response to cancer that can be detected in blood, urine, or tissue. Their main clinical roles include aiding in evaluation of disease burden, monitoring response to therapy, and detecting recurrence; however, the clinical utility—meaning evidence that use of the marker leads to improved health outcomes—varies by marker and indication.

Definitions and Test Descriptions

Tumor marker — definition and description

DefinitionA tumor marker is a substance (eg, protein, antigen, or hormone) detectable in blood, urine, or tissue that may indicate presence, progression, or recurrence of cancer.

Common usesUsed to assess response to therapy, monitor for recurrence, and sometimes reflect disease extent or stage.

ExamplesIncludes markers such as CEA, CA-125, CA 19-9, CA 15-3/27.29, 5-HIAA, HE4, and chromogranin A (CgA).

Laboratory-developed test (LDT) — definition

DefinitionLaboratory-developed test (LDT): a clinical laboratory test developed and validated in-house and subject to CLIA high-complexity standards.

Regulatory requirementLaboratories offering LDTs must be licensed under CLIA for high-complexity testing.

Line of Therapy Considerations

first-line

Line-of-therapy guidance for first-line treatment context

Use during first-line chemotherapy: HE4 and CA-125 have been evaluated during first-line platinum-based chemotherapy for prediction of response and progression; associations have been reported in observational studies (measurements commonly reported at diagnosis and after chemotherapy cycles, notably after the third cycle), but there is no evidence that biomarker-directed changes to first-line management improve clinical outcomes.

Studies measured markers at diagnosis and after cycles; no RCT evidence that altering first-line therapy based on these biomarkers improves survival.

Biomarker-specific Notes and Thresholds

HE4 — general note

Key takeawayNo established universal cutoff for HE4; study thresholds and FDA-reviewed cutoffs varied across publications and pivotal studies.

Example relative thresholdsFDA pivotal documents and studies used relative-change cutoffs such as 14% and 25% increases from prior measurements.

Example absolute thresholdsSome observational studies used absolute HE4 levels (eg, 70 pmol/L) as study-specific cutoffs.

CA-125 — key values

Common cutoff35 U/mL (commonly referenced as CA-125 upper limit of normal).

Trial-based action thresholdIn a randomized trial (Rustin et al.), action was taken when CA-125 exceeded twice the upper limit of normal (>2× ULN).

Policy Summary

PayerBlue Cross Blue Shield - South Dakota

PolicyTumor Markers in the Management of Malignancies — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateDec 1, 2020

Last ReviewFeb 1, 2025

Next Review DateN/A

Key ActionVerify member benefits and document indication, tumor marker tested, rationale, and how results will change management.

SourceLink

On This Page

Study cutoffs referenced

Examples in the literature include relative increases (14% and 25%) and absolute levels (e.g., 70 pmol/L, 199.20 pmol/L) depending on the assay and study design.

Clinical implicationClinicians may choose study-defined cutoffs or other thresholds based on desired sensitivity/specificity tradeoffs; standardized cutoff not defined.

When requested, providers should document the clinical intent for HE4 testing and how the test result is expected to change patient management given limited evidence that HE4-guided management improves health outcomes.

Justify indication (e.g., monitoring for recurrence, assessing residual disease) and expected management changes.

Billing Rule

Report tests using listed CPT codes

Claims for tumor marker assays must be reported using the CPT codes listed in the policy's Codes table when submitting provider services.

See Codes table for CPT codes including 86305 (HE4), 86304 (CA‑125), 86301 (CA 19‑9), 86300 (CA 15‑3/27.29), 82378 (CEA), 86316, 83497, and 84999.

Step Therapy

Use tumor markers in context of standard management

Consider standard diagnostic and management modalities—such as imaging, surgery, and systemic therapy—before relying on tumor marker testing alone to direct major treatment decisions.

Imaging (CT, MRI, PET) and clinical assessment are expected components of management alongside marker testing.

Step Therapy

Consider CA‑125 and imaging/clinical assessment before HE4

Before ordering HE4 alone, consider established markers and clinical assessments (for example CA‑125 and imaging) because evidence is insufficient to demonstrate that HE4 alone improves health outcomes.

HE4 has variable study cutoffs and no established universal threshold; use alongside CA‑125 and clinical evaluation.

Documentation Required

Verify member benefits and consult Codes table

Benefit determinations depend on the member's contract and applicable benefit language; verify individual member benefits prior to testing and consult the Codes table for billing details.

Verify coverage and any plan-specific requirements before ordering tests.

Documentation Required

Required clinical documentation with test request

Clinical documentation submitted with test requests should include the specific indication (cancer type and clinical scenario), the tumor marker(s) to be measured, patient/sample selection criteria, and the reference standard or serial measurement plan used for interpretation.

Examples: indication (e.g., monitoring for recurrence), marker name (HE4, CA‑125, CEA, CA19‑9, CA15‑3/27.29, 5‑HIAA, CgA), and rationale for testing.

Documentation Required

Document indication, rationale, and management impact for HE4/CA‑125

For HE4 and CA‑125, document the clinical indication, the rationale for ordering the test, and specifically how test results will change management; note that no standardized HE4 cutoff exists and study thresholds varied.

State intended use (e.g., assessing residual disease, monitoring for recurrence) and how a result would alter treatment decisions.

Billing Rule

Use appropriate procedure and diagnosis codes when reporting tests

When reporting laboratory tumor marker tests, use appropriate CPT, HCPCS, revenue, and ICD diagnosis codes as applicable to the service and clinical indication.

Use the Codes table in the policy for the specific CPT numbers to report.

Denial Risk

Risk of denial for investigational or non‑criteria testing

Requests for tests listed as investigational in the policy or for testing that does not meet the policy's medically necessary criteria may be denied.

The policy lists HE4 and other markers as investigational when criteria are not met.

Denial Risk

Denial risk when clinical utility is not demonstrated

Claims may be denied when testing lacks demonstrated clinical utility, has unclear placement in the clinical pathway, or when results would not change management to improve outcomes.

Denials are more likely when decision thresholds are not established or when evidence does not show improved health outcomes from test‑directed management.

Denial Risk

Denial risk for HE4 when clinical utility not demonstrated

For HE4 testing, absence of evidence that results change health outcomes or lack of demonstrated clinical utility may lead to denial of coverage when used to direct management decisions.

Policy highlights no prospective studies showing HE4‑guided management improves outcomes and notes variable cutoffs across studies.

Denial Risk

Coding omissions or errors may cause claim denial

Omission of appropriate CPT/HCPCS/revenue or ICD diagnosis codes, or incorrect coding on claims for tumor marker testing, can result in claim denial or payment issues.

Ensure inclusion of the correct CPT codes from the policy's Codes table (e.g., 86305 for HE4, 86304 for CA‑125, 86301, 86300, 82378, 86316, 83497, 84999).

Clinical noteLDTs are different from FDA-cleared kits, which undergo 510(k) review; both may be used in practice depending on laboratory capabilities.

Clinically valid — definition

DefinitionClinically valid: a test that detects the presence or absence of a condition, the risk of developing a condition, or treatment response (beneficial or adverse).

PurposeEstablishing clinical validity is a prerequisite for considering a test's potential clinical utility.

Evidence implicationInsufficient clinical validity evidence limits ability to infer that test use will improve health outcomes.

HE4 — definition and context

DefinitionHE4 (human epididymis protein 4): a serum biomarker evaluated for detection of recurrence and prediction of residual disease or chemotherapy resistance in epithelial ovarian cancer.

Regulatory contextMultiple HE4 assays have received FDA 510(k) clearance for use as an adjunct in monitoring epithelial ovarian cancer; serial testing should be used alongside other clinical methods.

Evidence summaryObservational studies and FDA data suggest HE4 may be noninferior to CA-125 for detecting recurrence, but superiority and impact on outcomes are not demonstrated.

Clinical utility — definition

DefinitionClinical utility: demonstration that use of a test leads to improved health outcomes, ideally shown by randomized controlled trials comparing management with and without the test.

Practical implicationEvidence of clinical utility is required to justify routine coverage; diagnostic performance alone is insufficient.

Policy consequenceTests lacking demonstrated clinical utility for a given indication are considered investigational or not medically necessary for that use.

Carcinoembryonic antigen (CEA) — code mapping

CEA CPT mapping82378

DescriptionCarcinoembryonic antigen (CEA).

Use noteReport using CPT 82378 for CEA serum assays as indicated in coding guidance.

Hydroxyindolacetic acid 5-HIAA — code mapping

5-HIAA CPT mapping83497

DescriptionHydroxyindolacetic acid (5-HIAA) — 24-hour urine assay for neuroendocrine tumors.

Use noteReport using CPT 83497 for 5-HIAA testing as specified in coding guidance.

CA 15-3 — code mapping

CA 15-3 CPT mapping86300

DescriptionImmunoassay for tumor antigen, quantitative; CA 15-3 (also reported as CA 27.29).

Use noteReport using CPT 86300 for CA 15-3/CA 27.29 assays when clinically indicated.

CA 19-9 — code mapping

CA 19-9 CPT mapping86301

DescriptionImmunoassay for tumor antigen, quantitative; CA 19-9.

Use noteReport using CPT 86301 for CA 19-9 serum testing per coding guidance.

CA 125 — code mapping

CA-125 CPT mapping86304

DescriptionImmunoassay for tumor antigen, quantitative; CA 125.

Use noteReport using CPT 86304 for CA-125 serum assays when indicated (eg, ovarian cancer evaluation, monitoring).

HE4 — code mapping

HE4 CPT mapping86305

DescriptionHuman epididymis protein 4 (HE4) immunoassay.

Use noteReport HE4 testing using CPT 86305; document clinical indication and how results will inform management.

Immunoassay other antigen (86316) — code mapping and examples

86316 CPT mapping86316

DescriptionImmunoassay for tumor antigen; other antigen, quantitative (eg, CA 50, 72-4, 549). This code may be used for Chromogranin A.

ExamplesMay be used to report quantitative immunoassays for other tumor antigens not listed with unique CPT codes (eg, Chromogranin A).

Unlisted chemistry procedure (84999) — code mapping

Unlisted chemistry CPT mapping84999

DescriptionUnlisted chemistry procedure — use when no specific CPT code accurately describes the performed assay.

Billing noteWhen reporting 84999, include documentation to support the service and consider payer-specific guidance for reimbursement.

Clinical implicationCA-125 rise alone did not improve overall survival when used to trigger earlier chemotherapy in the cited trial.

CA 19-9 — key values

Primary CPT code86301

DescriptionImmunoassay for tumor antigen, quantitative; CA 19-9.

IndicationsUsed for pancreatic, biliary, gastric, ampullary, mucinous appendiceal, ovarian indications per policy guidance.

CA 15-3 (CA 27.29) — key values

Primary CPT code86300

DescriptionImmunoassay for tumor antigen, quantitative; CA 15-3 (also reported as CA 27.29).

IndicationsFollowing course of treatment in individuals with breast cancer, especially advanced/metastatic disease.

CEA — key values

Primary CPT code82378

DescriptionCarcinoembryonic antigen (CEA) — multiple oncologic indications including colorectal cancer and others per policy.

Clinical noteAlso used in pancreatic cyst fluid to distinguish mucinous from non-mucinous cysts when appropriate.

Chromogranin A (CgA) — key values

CgA potential code86316

DescriptionChromogranin A (CgA) is used in neuroendocrine tumors and may be reported using immunoassay-other antigen CPT 86316 per coding guidance.

Clinical useCgA may be considered for neuroendocrine tumor evaluation and follow-up as listed in the policy indications.

5-HIAA — key values

Primary CPT code83497

Description5-HIAA (24-hour urine) for neuroendocrine tumors.

Clinical noteUse CPT 83497 when reporting 24-hour urinary 5-HIAA testing per coding guidance.

HE4 — examples of study cutoffs

Study examplesRelative-change study cutoffs reported include 14% and 25% increases from prior HE4 measurements; absolute cutoffs reported include 70 pmol/L and a 199.20 pmol/L example in the literature.

Source context14% and 25% relative increases were used in FDA-pivotal and prior assay studies; observational studies used absolute levels like 70 pmol/L.

ImplicationVariation in cutoffs across studies underscores lack of a universally accepted HE4 threshold for monitoring.

CA-125 — commonly referenced cutoffs

Commonly referenced ULN35 U/mL (CA-125 upper limit of normal).

Trial action thresholdIn the cited randomized trial, CA-125 >2× ULN was used to trigger early chemotherapy assignment.

Outcome noteEarly treatment based on CA-125 doubling did not improve overall survival in that trial.

Other markers — key values

Other markers and codesCEA (82378), CA19-9 (86301), CA15-3/27.29 (86300), 5-HIAA (83497), Chromogranin A (may use 86316).

Clinical useThese markers are indicated for specific tumor types as listed in the policy (eg, colorectal, pancreatic, breast, neuroendocrine).

Coding noteReport assays using the listed CPT codes and include clinical documentation of indication and expected management impact.

HE4 — reiterated note

ReiterationNo established universal HE4 cutoff; thresholds varied across studies and pivotal FDA submissions; clinical interpretation should reference assay-specific data and study cutoffs.

Clinical guidanceConsider HE4 results alongside CA-125 and other clinical/imaging data rather than as a solitary trigger for major management changes.

DocumentationDocument assay used, cutoff applied (if any), and how the result will influence patient management when reporting HE4 testing.

CA-125 — trial threshold detail

Trial threshold used>2× upper limit of normal (doubling above ULN) was the threshold used in the randomized Rustin et al. trial.

OutcomeNo overall survival benefit was observed for early treatment triggered by this CA-125 threshold.

Clinical implicationUse of CA-125 to trigger earlier treatment should be weighed against evidence showing no survival benefit in that context.

CEA — code/key-value

CEA code82378

UseCarcinoembryonic antigen (CEA) — report using CPT 82378.

NoteInclude clinical indication when submitting claims for CEA testing.

CA 15-3 — code/key-value

CA 15-3 code86300

UseImmunoassay for tumor antigen, quantitative; CA 15-3 (CA 27.29).

NoteReport with clinical indication for breast cancer monitoring when applicable.

CA 19-9 — code/key-value

CA 19-9 code86301

UseImmunoassay for tumor antigen, quantitative; CA 19-9.

NoteReport with appropriate clinical indication for pancreatic, biliary, gastric, or other relevant cancers.

CA 125 — code/key-value

CA-125 code86304

UseImmunoassay for tumor antigen, quantitative; CA 125 — used for ovarian and other gynecologic malignancy indications per policy.

NoteDocument indication and any thresholds applied when reporting CA-125 testing.

HE4 — code/key-value

HE4 code86305

UseHuman epididymis protein 4 (HE4) immunoassay — report using CPT 86305.

NoteDocument assay method and any study-based cutoff applied; HE4 interpretation should be adjunctive to clinical/imaging data.

Chromogranin A — code/key-value

Chromogranin A code86316

UseImmunoassay for tumor antigen; other antigen, quantitative — may be used for Chromogranin A reporting.

Clinical noteChromogranin A is indicated for neuroendocrine tumors and select occult primaries per policy.

5-HIAA — code/key-value

5-HIAA code83497

UseHydroxyindolacetic acid (5-HIAA) — report using CPT 83497 for 24-hour urine assays.

Clinical noteIndicated for neuroendocrine tumor evaluation and monitoring as outlined in the policy.