Serum Tumor Markers for Malignancies (Routine Test Management Policy)
This policy governs reimbursement and clinical indications for measurement of serum tumor biomarkers for diagnosis, staging, monitoring, and surveillance of malignancy for Premera Blue Cross members.
Policy Summary
PayerPremera Bluecross
PolicySerum Tumor Markers for Malignancies (Routine Test Management Policy)
Policy CodePolicy G2124
Change TypeNew policy + coding update
Effective DateFeb 6, 2026
Next Review Date
Key ActionDocument the specific covered clinical indication on all tumor marker orders and adhere to the policy-listed frequency and sequencing when ordering tests.
New policy added to the Routine Test Management Policy specifying that measurement of specified serum tumor markers is reimbursable only for the indications outlined in this policy.
Use of these biomarkers for other cancer indications, any unlisted serum tumor markers, or proteomic pattern analysis for cancer screening is not reimbursable due to insufficient evidence.
Coding update removed CPT codes 83789 and 83880.
1New policy added (history)
02/06/26Coding update date
90 daysProvider notification prior to effective date
not reimbursableUnlisted/unsupported use
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q6mAFP HCC interval
Coverage Criteria and Medical Necessity
AFP and Related Markers for Hepatocellular Carcinoma
AFP and related markers for hepatocellular carcinoma (HCC) — Measurement of alpha-fetoprotein (AFP) and related markers (AFP‑L3%, DCP/PIVKA‑II) is reimbursable when used for screening, surveillance, prognostic evaluation, or monitoring of confirmed HCC as specified below.
ANY of the following:
ANY of the following
AFP measurement for individuals at high risk for hepatocellular carcinoma (eg, persons with cirrhosis or chronic hepatitis B) for surveillance, performed at approximately 6‑month intervals; an AFP concentration >20 μg/L should prompt further investigation even if imaging is negativeAFP >20 μg/L
Aligns with ADLM guidance recommending 6‑month surveillance intervals and investigation of sustained elevations.
AFP measurement for workup, staging, or monitoring of confirmed HCC, including use to establish baseline, assess treatment response, and for post‑treatment surveillance (eg, every 3–6 months for 2 years, then every 6 months as clinically indicated)
AFP may provide prognostic information and is appropriate as part of disease monitoring.
Measurement of AFP‑L3% and/or DCP (also reported as PIVKA‑II) when used as adjuncts to AFP and imaging for risk stratification, prognostic assessment, or surveillance of HCC, where clinical decision‑making is informed by combined marker results
Considered supportive when used in combination; evidence suggests AFP‑L3% and DCP may add prognostic or detection utility in selected contexts.
Use of a combined biomarker approach (eg, AFP with PIVKA‑II and/or AFP‑L3) to improve detection or prognostic assessment of HCC when clinical management will be influenced by results
Coverage contingent on documentation that results will influence monitoring, diagnostic, or therapeutic decisions (eg, listing for transplant, changes in surveillance imaging or treatment planning).
Hepatocellular Carcinoma (AFP) — ADLM Guidance
ADLM guidance on HCC (AFP) — Recommendations from the Association for Diagnostics & Laboratory Medicine (ADLM) regarding AFP use in HCC management are summarized to guide coverage.
ALL of the following:
ALL of the following
AFP may be used for surveillance in patients at high risk for hepatocellular carcinoma, with measurement approximately every 6 months
ADLM recommends 6‑month intervals for high‑risk individuals.
AFP concentrations above 20 μg/L should prompt further evaluation, even in the absence of suspicious ultrasound findingsAFP >20 μg/L
ADLM cites this threshold as a trigger for additional diagnostic workup.
AFP measurement may be used for monitoring and prognostic assessment in patients with known HCC; sustained increases can inform detection and management when used with imaging
Marker-Specific Covered Indications
Marker-by-marker mapping to cancer types and monitoring frequency
Marker-by-marker mapping to cancer types and recommended monitoring frequency (examples):
AFP: Indications include HCC (screening, workup, surveillance), intrahepatic cholangiocarcinoma workup, occCult primary and multiple ovarian/testicular tumor indications; surveillance frequency for HCC: every 3–6 months for 2 years then every 6 months (ADLM/AASLD guidance noted elsewhere).see policy
See chunks 4, 26–28 for details and thresholds
CA 19-9: Indications include pancreatic, ampullary, cholangiocarcinoma, gallbladder, and select ovarian tumors for workup and surveillance; typical surveillance: every 3–6 months for 2 years then every 6–12 months as clinically indicated.see policy
See chunks 8–9 and 36 for study-specific cutoffs
Testing Frequency and Surveillance Intervals
Examples of surveillance intervals (policy examples)
AFP (HCC)Every 3-6 months for 2 years, then every 6 months (surveillance after HCC) — example surveillance interval from policy indications.
CA 19-9 (pancreatic/ampullary)Every 3-6 months for 2 years, then every 6-12 months as clinically indicated (post-resection surveillance).
CEA (colorectal)Every 3-6 months for 2 years, then every 6 months for a total of 5 years (CRC surveillance example).
Germ cell markers (AFP, hCG, LDH)No more than every 2 months initially for malignant germ cell tumor surveillance (frequency varies by stage/time since treatment).
CA-125 (ovarian)If initially elevated, monitoring at each visit for borderline epithelial tumors; frequency based on stage for sex cord/stromal tumors (e.g., 6-12 months if low-risk).
Billing Codes and Code-Level Notes
Covered CPT/HCPCS Codes (listed)mixed
82105
Alpha-fetoprotein (AFP); serum.
82107
Alpha-fetoprotein (AFP); AFP-L3 fraction isoform and total AFP (including ratio).
Phosphatase, alkaline; heat stable (total not included).
1–10 of 21
1/3
Removed CPT CodesCPT
83789
CPT code removed from policy
83880
CPT code removed from policy
Surveillance frequency examples for coding context
AFP for HCC (example)Every 3-6 months for 2 years, then every 6 months — example surveillance schedule for AFP in HCC from policy indications.
CA19-9 (pancreatic) exampleEvery 3-6 months for 2 years, then every 6-12 months — example surveillance schedule for pancreatic/ampullary cancers.
Germ cell marker exampleNo more than every 2 months initially for malignant germ cell tumor surveillance (policy example).
AFP recurrence risk threshold
AFP recurrence risk threshold>200 ng/mL — AFP level associated with higher recurrence risk after liver transplant (study by Santos Schraiber et al.).
Prognostic implication
Ordering, Documentation, and Prior Authorization
Prior Authorization
Code-level prior authorization / code listing
Prior authorization is determined at the code level. Providers should bill only for the CPT/HCPCS codes listed in the policy when ordering reimbursable serum tumor marker tests. Use of codes for indications not described in this policy or use of unlisted/experimental proteomic analyses may be denied.
Only CPT/HCPCS codes enumerated in the policy are eligible for reimbursement under the described indications.
Claims using codes for unlisted tumor markers, proprietary proteomic pattern analyses, or for unsupported indications may be denied.
Documentation Required
Ordering of FDA-approved ovarian biomarker panels
FDA-cleared ovarian biomarker panels (ROMA, OVA1, OVERA) are intended for use only in patients with an adnexal/pelvic mass when surgery is planned and the patient has not yet been referred to an oncologist. Documentation of the planned surgery and clinical context must be included in the medical record.
How to Order and Document Tests
Note
Order tests only for policy‑listed indications and follow frequency guidance
Ordering must be tied to the clinical indications listed in the policy and adhere to specified frequency guidance where provided; document indication on the order.
Link each test order to a covered indication (workup, monitoring, surveillance).
Follow policy frequency limits when specified (e.g., surveillance intervals).
Documentation Required
Document indication and management impact; follow sequential algorithms
The ordering clinician should document the clinical indication and how the biomarker result will inform patient management; when sequential algorithms apply, follow and document the sequence.
Record how results will affect treatment/referral decisions.
When sequential testing is described (e.g., Ova1 → Overa), document initial results and rationale for next test.
Tests and Uses Not Covered
Proteomic pattern analysis in serum for cancer screening and detection is not covered. The policy explicitly excludes proteomic analyses for screening purposes and states that any serum tumor markers or panels not addressed in the policy are not reimbursable due to insufficient evidence of clinical benefit.
Proprietary or commercial tests intended as standalone replacements for standard diagnostic procedures are not supported. The policy describes such tests as adjunctive and notes their clinical validity and utility are still emerging; they are not intended to replace established diagnostic modalities (for example, colonoscopy) and use as a standalone substitute is not covered.
Proteomic analyses and many investigational protein biomarkers remain investigational and are not appropriate for routine clinical use. The policy cites proteomics research and individual marker studies but concludes that such approaches lack the validated clinical utility required for reimbursement in routine care.
Multiple specific markers are identified as not recommended for routine use or screening. Examples include Glypican‑3 for HCC, various bladder cancer markers, routine SCC for cervical cancer prognosis, CA 19‑9/CA 242/TIMP‑1 for CRC prognosis, CA 15‑3/CEA for early breast cancer detection, and many ovarian or pNET markers that do not meaningfully change management; these uses are considered unsupported for routine screening.
Any serum tumor markers or proteomic pattern analyses not listed in this policy are not covered. The policy reiterates that unlisted markers and proteomic pattern analysis for cancer screening lack sufficient evidence and are excluded from reimbursement.
Definitions and Background
Background: Circulating tumor biomarkers are substances detectable in blood, urine, or other body fluids that are produced by tumors or generated in response to tumor presence. They can assist with detection, diagnosis, staging, prognosis, and monitoring in certain malignancies, but their utility varies by marker and clinical context. This policy focuses on serum‑measured tumor markers and aligns recommended uses with evidence and professional society guidance (for example, the NCCN Biomarkers Compendium and ADLM guidance).
Definition — Circulating tumor biomarkers
DefinitionCirculating tumor biomarkers are substances detected in blood, urine, or other body fluids produced by a tumor or in response to a tumor; used to aid detection, diagnosis, staging, and management of some cancers.
SpecimenThis policy focuses on tumor markers measured in serum.
Guideline basisPolicy approach built from recommendations in the NCCN Biomarkers Compendium and other professional guidelines.
Terminology — common marker abbreviations
Policy Summary
PayerPremera Bluecross
PolicySerum Tumor Markers for Malignancies (Routine Test Management Policy)
Policy CodePolicy G2124
Change TypeNew policy + coding update
Effective DateFeb 6, 2026
Next Review Date
Key ActionDocument the specific covered clinical indication on all tumor marker orders and adhere to the policy-listed frequency and sequencing when ordering tests.
ADLM supports AFP for monitoring and as a prognostic marker in untreated patients.
Routine measurement of alternative liver biomarkers (eg, Glypican‑3) is not recommended outside of research settings due to insufficient evidence
ADLM does not currently endorse other liver biomarkers for routine clinical management.
CEA: Indications include colorectal, appendiceal, metastatic breast, and other adenocarcinomas for baseline, monitoring, and surveillance; CRC surveillance frequency example: every 3–6 months for 2 years then every 6 months up to 5 years.see policy
See chunks 11 and 55 for ADLM recommendations
Serum free light chains: Indications include multiple myeloma, AL amyloidosis, and other monoclonal gammopathies for diagnostic workup, baseline prognostic assessment, and monitoring (may be measured up to once per month for surveillance when indicated).
Order with SPEP and immunofixation per ADLM
BNP/NT-proBNP and Troponin: Used for evaluation of cardiac involvement in systemic light-chain amyloidosis and multiple myeloma as part of initial diagnostic workup and monitoring of organ involvement.
See chunks 31 and 44 for context
Diagnosis, prognosis, risk stratification, and monitoring of specific malignancies
Diagnosis, prognosis, risk stratification, and monitoring of specific malignancies
HCC: AFP (and related markers AFP-L3% and PIVKA-II/DCP) used for management, prognostication, and surveillance in hepatocellular carcinoma when interpreted with imaging and clinical context.AFP >200 ng/mL associated with higher recurrence risk; AFP-L3 >10%; PIVKA-II >40 mAU/mL in combined algorithms
See meta-analyses and cohort studies cited
Medullary thyroid carcinoma: Calcitonin used for diagnosis and postoperative monitoring of medullary thyroid carcinoma; measure with CEA and TFTs per ATA guidance.
Postoperative monitoring every 6–12 months
Cardiac involvement in plasma cell disorders: BNP/NT-proBNP and troponin used to assess cardiac involvement in systemic light-chain amyloidosis and to inform staging and prognosis.
Use as part of multimodal assessment
Ovarian risk assays: FDA-cleared multi-biomarker assays (ROMA, OVA1, OVERA, OvaWatch) may be used for preoperative risk estimation or risk refinement in indeterminate adnexal masses when used per intended indications and algorithms.
Order and interpret per manufacturer and guideline recommendations
AFP for management and surveillance of HCC; pretreatment AFP/LDH/hCG for suspected testicular cancer
AFP and related markers for HCC; pretreatment tumor markers for testicular cancer
AFP for HCC management and surveillance: AFP is supported for management and surveillance of HCC; ADLM/AASLD recommend surveillance intervals and note AFP >20 μg/L should prompt investigation; pretreatment AFP (with LDH and hCG where relevant) is used in testicular cancer staging and monitoring.AFP > 20 μg/L triggers further workup; AFP >200 ng/mL associated with recurrence risk
See chunks 26–28 and 54–55
Serum free light chains for plasma cell disorders and light chain amyloidosis
Serum free light chains for plasma cell disorders and amyloidosis
SFL for diagnosis and monitoring: Serum free light chain assays are reimbursable for diagnosis, prognosis, baseline assessment, and monitoring of plasma cell disorders and light-chain (AL) amyloidosis when ordered with SPEP and immunofixation; interpret kappa and lambda absolute values and ratio while recognizing assay limitations.
ADLM recommends SFL for determining stringent complete remission and following oligosecretory disease
Serum tryptase for systemic mastocytosis and NET marker guidance
Tryptase and neuroendocrine markers
Serum tryptase is an accepted diagnostic marker for systemic mastocytosis and mast cell activation disorders and is reimbursable when used for these diagnostic indications.
Tryptase elevation is a diagnostic criterion per specialty guidance
CgA and pancreastatin for NETs: Chromogranin A and pancreastatin are not recommended for routine use in pancreatic neuroendocrine tumors because they rarely influence treatment; selective use may be considered by clinicians but routine surveillance is not supported.
NANETS guidance advises against routine measurement
HCC surveillance in high-risk patients
HCC surveillance in high-risk patients
HCC surveillance interval: In high-risk patients for hepatocellular carcinoma, measure AFP every 6 months; concentrations above 20 μg/L should prompt further investigation even if ultrasound is negative.AFP > 20 μg/L
ADLM/AASLD guidance incorporated into surveillance recommendations
Surveillance of stage II/III colorectal cancer
Surveillance of stage II/III colorectal cancer and CEA monitoring
CEA surveillance for stage II/III CRC: Measure CEA every 3 months in stage II or III colorectal cancer when the patient is a candidate for surgery or systemic therapy; use pre-operative CEA in surgical planning and continue surveillance per guideline intervals.every 3 months where indicated
ADLM recommends CEA for perioperative surveillance
Screening and monitoring plasma cell disorders
Screening and monitoring plasma cell disorders
SFL with SPEP/IFE: When screening for monoclonal gammopathies, order serum free light chains together with serum protein electrophoresis and immunofixation; use for diagnosis, baseline prognostication, and monitoring of multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, and MGRS.
Follow ADLM recommendations for frequency and interpretation
Specified serum tumor markers when ordered for the indications outlined in the policy
Specified serum tumor markers when ordered for the indications outlined in the policy
Routine Test Management incorporation: Measurement of specified serum tumor markers referenced in this policy has been added to the Routine Test Management Policy; reimbursement is limited to the indications and frequencies outlined herein.
See policy history for effective dates and coding changes
OvaWatch — role and use
OvaWatch useOvaWatch may be considered for ovarian cancer risk refinement for individuals with an adnexal mass who are not planned for surgery when initial assessment is indeterminate or benign.
Intended roleUsed as a risk-refinement adjunct combining seven tumor biomarkers with age and menopausal status to produce a risk score (reported NPV 99%).
Clinical context requiredShould be used when initial clinical/imaging assessment is indeterminate or benign and results will inform management decisions.
ASCO surveillance schedule for germ cell tumor markers
MarkersAFP and hCG (and LDH as indicated) are recommended for use in adult males with germ cell tumors per ASCO guidance.
Timing around treatmentMeasure AFP and hCG before orchiectomy to establish baseline; measure immediately prior to chemotherapy and at the start of each chemotherapy cycle; measure when chemotherapy concludes.
Surveillance durationASCO recommends surveillance measurement of AFP and hCG during follow-up for at least 10 years after therapy concludes.
AFP and HCC surveillance notes (ADLM)
Recommended intervalMeasure AFP at 6-month intervals in patients at high risk for hepatocellular carcinoma (ADLM recommendation).
Trigger for further evaluationAFP concentrations above 20 μg/L should prompt further investigation even if ultrasound is negative.
Use with imagingSustained increases in AFP may be used in combination with ultrasound to inform detection and management of HCC.
AFP recommended interval — 6 months
Recommended intervalEvery 6 months for HCC surveillance in high-risk patients (ADLM practice guideline).
Surveillance contextAFP used for screening and monitoring in high-risk patients; integrate with imaging findings for diagnosis and management.
Action thresholdSustained increases or AFP >20 μg/L should prompt further diagnostic evaluation even if ultrasound is negative.
AFP for HCC — surveillance frequency
Interval for surveillanceEvery 6 months — recommended AFP testing interval for hepatocellular carcinoma surveillance in high-risk patients.
IntegrationAFP measurement should be interpreted alongside ultrasound and other clinical data; sustained rises warrant further workup.
Use caseApplies to screening and monitoring of HCC and to management decisions where AFP is informative per ADLM guidance.
CEA surveillance for stage II/III colorectal cancer
Recommended intervalEvery 3 months — measure CEA every 3 months in stage II or III colorectal cancer when patient is a candidate for surgery or systemic therapy.
Surveillance courseCEA measured every 3-6 months for 2 years, then every 6 months for a total of 5 years is described in broader CRC surveillance guidance.
Pre-operative usePre-operative CEA may inform surgical planning and baseline assessment.
Frequency limits — general placeholder
Frequency limits placeholderPolicy provides marker- and indication-specific surveillance intervals; where unspecified, quarterly measurement is permitted as the default monitoring frequency.
Apply guideline-specific intervalsWhen professional society guidance or policy-specified intervals exist, follow those instead of default quarterly frequency.
DocumentationProviders should document indication and intended use when ordering to support adherence to frequency limits.
AFP >200 ng/mL was associated with a 3.32-fold increased probability of HCC recurrence in the cited study.
Clinical useHigh AFP levels may inform prognosis and post-treatment surveillance intensity in HCC patients.
AFP-L3 percent threshold
AFP-L3 percent threshold>10% — AFP-L3% reported in studies as an elevated fraction associated with poorer prognosis in HCC; adding AFP-L3 did not improve diagnostic AUC in one study when combined with PIVKA-II and AFP.
Interpretation noteHigh AFP-L3% has been associated with worse overall and disease-free survival in meta-analysis (Cheng et al.).
Use in panelsAFP-L3% may be considered in combination algorithms but evidence of additive diagnostic value is mixed.
PIVKA-II threshold and combination with AFP
PIVKA-II with AFPPIVKA-II > 40 mAU/mL combined with AFP > 10 ng/mL — reported combination yielding the highest AUC in a cited comparative study.
Diagnostic performanceCombination of PIVKA-II and AFP improved diagnostic AUC compared to individual markers in the cited study; adding AFP-L3 worsened performance.
Clinical implicationCombined marker algorithms may improve diagnostic accuracy for HCC compared to single markers in some studies.
CA19-9 and CA-125 diagnostic cutoffs (study-specific)
CA19-9 diagnostic cutoff (study)CA19-9: 252.31 U/mL — study-reported cutoff for gallbladder cancer with high sensitivity/specificity in that cohort.
CA-125 diagnostic cutoff (study)CA-125: 92.19 U/mL — reported cutoff in same study for gallbladder cancer with high sensitivity/specificity.
Study contextCutoffs are study-specific (Bind et al.) and should be interpreted in context with imaging and clinical findings.
Extremely high LDH example
Extremely high LDH example>1000 U/L — extremely high LDH level used in a study and associated with poor overall survival (example cohort with very short OS).
Prognostic notePatients with LDH >1000 U/L had markedly reduced survival in the cited study; decreases after therapy correlated with better outcomes.
Clinical useVery high LDH values may indicate aggressive disease and inform prognosis; interpret with cancer type and clinical context.
Chromogranin A cutoff (example study)
Chromogranin A cutoff example46.2 ng/mL — study-reported cutoff with sensitivity 78.8% and specificity 73.8% for neuroendocrine tumors.
Biomarker variabilityCgA is variably elevated in NETs and subject to assay and clinical confounders; routine use is not uniformly recommended.
Clinical interpretationUse CgA results alongside imaging and clinical features; cutoffs may vary by assay and cohort.
Ova1 generally performed first; if indeterminate, Overa may be performed to refine risk.
Use of these tests in patients not planned for surgery or to substitute for specialist evaluation is not supported by NCCN guidance and may be denied.
Note
Prior authorization / LDT note
Laboratory-developed tests (LDTs) are permitted under CLIA but are not FDA-approved; labs must validate analytic performance. Prior authorization requirements may apply per payer rules—coverage is contingent on proper laboratory validation and documentation of clinical utility.
LDTs must be performed in CLIA-certified high-complexity laboratories and have documented analytic validation.
Lack of appropriate laboratory validation or evidence of clinical utility may affect coverage decisions.
Prior Authorization
Prior authorization
No additional, separate prior authorization program is specified for most routine serum tumor marker tests in this section. However, authorization and reimbursement depend on meeting the policy's clinical indication and documentation requirements; tests performed for unsupported indications may be denied.
Follow payer-specific prior authorization portals if applicable for other services; clinical documentation must support the test indication.
Denial Risk
Denial triggers for unsupported indications/tests
Tests ordered for indications not described in this policy, use of unlisted serum tumor markers, proteomic pattern analysis for cancer screening, or proprietary panels lacking established clinical validity/utility are subject to denial.
Claims for tumor marker use outside the policy-listed indications are not reimbursable.
Proprietary tests with insufficient published evidence may be denied without strong supporting documentation.
Documentation Required
Use of proprietary serum tumor marker tests
Proprietary serum tumor marker tests (commercial panels and proteomic assays) have emerging and variable evidence. Providers ordering these tests should document analytic validity, clinical validity, and demonstrated clinical utility in the patient's record to justify use for management decisions.
Provide rationale linking the test result to a specific management decision or guideline-supported action.
Proprietary screening tests without robust validation are generally not reimbursable.
Denial Risk
Adnexal mass biomarker use warning
NCCN does not recommend using certain biomarker tests to determine the status of an undiagnosed adnexal/pelvic mass. Use of these panels in lieu of specialist evaluation or surgery planning may lead to non-coverage.
Refer patients with suspected ovarian malignancy to an experienced gynecologic oncologist prior to surgery.
Biomarker panels may be adjunctive but are not a substitute for clinical/imaging evaluation and specialist referral.
Note
LDT regulatory/compliance risk
Because LDTs are regulated under CLIA rather than FDA, there is regulatory and compliance risk if the performing laboratory lacks appropriate validation documentation. Payers may deny coverage if laboratory validation or certification is inadequate.
Ensure the performing lab is CLIA-certified for high-complexity testing and has documented analytic validation.
Maintain lab reports and validation summaries in the medical record when ordering LDTs.
Denial Risk
Denial triggers for unlisted/unsupported tumor marker use
Claims for use of tumor markers outside listed indications, for unlisted serum tumor markers, or for proprietary proteomic analyses for cancer screening may be denied due to insufficient evidence of clinical benefit.
Denial risk is higher for tests lacking published peer-reviewed evidence of clinical utility.
Documented clinical rationale and adherence to guideline-recommended indications reduce denial risk.
Documentation Required
Documentation of indication and frequency
Providers must document the specific clinical indication and, when applicable, the testing frequency consistent with guideline recommendations and the policy (e.g., AFP for HCC surveillance every 3–6 months for 2 years, then every 6 months). Medical records should clearly link the ordered test to the covered indication.
Include diagnosis, clinical context, planned procedures (e.g., planned adnexal surgery), and surveillance interval when applicable.
For surveillance testing, document prior baseline values and the reason for repeated measures.
Documentation Required
Clinical validity, analytic validity, and clinical utility
Before ordering proprietary or novel panels, document analytic validity (test performance and lab validation), clinical validity (association with diagnosis or outcome), and clinical utility (evidence that results change management or improve outcomes). Tests lacking this evidence are unlikely to be covered.
Attach or reference peer-reviewed evidence or guideline recommendations supporting the test for the specific clinical scenario.
For novel tests, specify how the test result will influence treatment, referral, or surveillance decisions.
Billing Rule
When multi-step testing algorithms are described
When multi-step testing algorithms are described (for example, OVA1 first, then OVERA if indeterminate), providers should follow the stepwise protocol and document each step and its result in the medical record to support subsequent testing and coverage.
Do not bypass required sequencing (performing Overa without documented indeterminate Ova1) unless clinically justified and documented.
Document the indeterminate result and rationale for proceeding to the next-step assay.
Documentation Required
Timing requirements for germ cell tumor markers
For germ cell tumors, measure AFP, hCG, and LDH at recommended time points: before orchiectomy to establish baseline, immediately prior to chemotherapy for staging/stratification, at the start of each chemotherapy cycle, at treatment conclusion, and during surveillance per guideline intervals (frequent early follow-up; see ASCO intervals).
Surveillance intervals: every 2–4 months in year 1, every 3–4 months in year 2, every 4–6 months in years 3–4, and annually thereafter up to at least 10 years.
Document baseline and serial measurements in the medical record to support monitoring and reimbursement.
Note
None specified in these sections
No additional provider actions were specified for the remaining sections beyond those summarized above.
Note
Use FDA‑approved ovarian assays only in indicated preoperative patients
Use FDA‑approved multi‑biomarker assays (ROMA, OVA1, OVERA) only in patients who meet the FDA indication — preoperative patients with an adnexal mass planned for surgery — and document the surgical plan and referral status.
Confirm and document that surgery is planned and patient has not been referred to an oncologist.
Do not use these assays outside the FDA‑cleared preoperative indication.
Note
Obtain germ cell markers before orchiectomy and follow ASCO timing
Order AFP, hCG, and LDH (as indicated) for suspected testicular cancer prior to orchiectomy and then per ASCO‑recommended intervals during treatment and surveillance; document timing of each measurement relative to operative and treatment events.
Obtain pre‑orchiectomy AFP and hCG as baseline.
Follow ASCO surveillance intervals (e.g., every 2–4 months year 1, then extending intervals up to annual; continue surveillance for at least 10 years).
Note
Order serum free light chains with SPEP and immunofixation for monoclonal workup
Order serum free light chain testing together with serum protein electrophoresis (SPEP) and immunofixation when screening for monoclonal gammopathies (e.g., multiple myeloma, AL amyloidosis); document combined use on orders.
Include SPEP and immunofixation on the order when requesting serum free light chains for screening.
Document clinical suspicion for a monoclonal process to support testing.
Note
No specified ordering provider restrictions in excerpt — follow plan limits
No provider‑level ordering restrictions are specified in this excerpt; providers should follow member benefit limits and the Routine Test Management Policy for plan‑specific restrictions.
Check member benefit booklet or contact member services for any plan limits.
Follow Routine Test Management Policy details where applicable.
AFPAlpha fetoprotein (AFP).
CA-125 / CA 19-9 / CEACA-125 (Cancer antigen 125), CA 19-9 (Cancer antigen 19-9), CEA (Carcinoembryonic antigen).
ALP / LDH / hCGALP (Alkaline phosphatase), LDH (Lactate dehydrogenase), beta-hCG (beta human chorionic gonadotropin).
NT-proBNPN-terminal pro hormone B-type natriuretic peptide — used to assess cardiac involvement (e.g., in light-chain amyloidosis).
Clinical roleMay inform organ-specific involvement and prognosis in plasma cell disorders and amyloidosis.
Interpretation noteUse alongside clinical assessment and other cardiac biomarkers (troponin) for evaluation.
PAM50-ROR — definition
PAM50-RORPrediction Analysis of Microarray 50 — Risk of Recurrence (PAM50-ROR) — a genomic risk classifier for breast cancer recurrence.
Clinical contextUsed to estimate risk of recurrence and inform adjuvant therapy decisions in selected breast cancer patients.
Relation to markersDistinct from serum tumor markers; included as a terminology entry in policy tables.
TILs — definition
TILsTumor-infiltrating lymphocytes (TILs) — immune cells present within tumors; used as a pathological/biologic marker rather than a circulating serum tumor marker.
Clinical relevanceTILs inform prognosis and potential response to immunotherapy in some cancers.
distinctionListed in terminology table to clarify definitions used across the policy.
Serum free light chains — definition and use
Serum free light chains (FLC)Assays quantify free kappa and lambda light chains in serum and their ratio to aid diagnosis, prognosis, and monitoring of plasma cell disorders and AL amyloidosis.
Use with other testsOrder alongside serum protein electrophoresis (SPEP) and immunofixation for suspected monoclonal gammopathies.
Interpretation noteConsider absolute values and kappa/lambda ratio; be aware of assay limitations and inter-assay variability.
Troponin — definition and relevance
Troponin (TnI/TnT)Cardiac troponins (TnI, TnT) — proteins used as biomarkers of cardiac injury; elevated levels may indicate cardiac involvement in systemic light-chain amyloidosis.
Clinical applicationPersistently elevated cardiac troponins frequently observed in amyloidosis and can inform prognosis and management.
InterpretationUse in conjunction with NT-proBNP and clinical assessment for cardiac involvement evaluation.
Tryptase — definition and use
TryptaseTryptase — a mast cell protease measured in serum to support diagnosis of mast cell disorders such as systemic mastocytosis (accepted diagnostic criterion).
Clinical roleElevated tryptase supports diagnosis of mast cell activation disorders and systemic mastocytosis.
Testing contextInterpret results alongside clinical history and other diagnostic criteria (e.g., bone marrow findings).
Laboratory-developed test (LDT) — definition and regulatory note
Laboratory-developed test (LDT)A test developed and validated within a laboratory for clinical use; regulated by CMS as high-complexity tests under CLIA '88 and not FDA-cleared/approved.
Regulatory noteLDTs are performed under CLIA and require laboratory validation; FDA clearance is not required for clinical use under current practice.
Coverage implicationUse of proprietary/commercial LDT panels may be scrutinized; documentation of intended adjunctive use is recommended.
Tumor marker — definition
Tumor marker — definitionTumor markers are serum biomarkers used for diagnosis, prognosis, surveillance, or monitoring of certain cancers as referenced in literature and guidelines.
Specimen typePolicy focuses on serum-measured tumor markers; many markers can be organ- or tumor-specific or nonspecific.
Use constraintsMarkers should be used in tumor-specific clinical contexts and interpreted alongside imaging and clinical findings per guideline recommendations.