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Date Printed: August 18, 2017: 10:21 AM

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05-86000-22

Original Effective Date: 02/15/04

Reviewed: 12/01/16

Revised: 08/01/17

Subject: Tumor/Genetic Markers

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
           
Other References Updates    
           

DESCRIPTION:

Serum tumor markers are molecules or substances shed by a tumor into the circulation where they can be detected and quantitated. Noncirculating tumor markers include those that can be detected histochemically or cytogenetically on a tissue sample.

Since serum tumor markers can also be detected in normal or benign lesions, significantly elevated circulating levels may occur with malignancy by one or more of the following mechanisms: overexpression of the antigen by malignant cells; a large tumor burden; or slower clearance of the marker. For example, since the liver clears most tumor markers, liver abnormalities (whether benign, malignant, or inflammatory) may elevate tumor marker concentrations due to impaired clearance. Because most tumor markers are not unique to malignancy, cut-off points must be established for normal versus abnormal marker levels.

The clinical applicability of tumor markers depends on how their measurements are used to influence the management of the patient and whether these management changes will result in an improvement in net health outcome.

POSITION STATEMENT:

Biochemical Markers
of Alzheimer’s Disease

(AlzheimAlert™, AdMark®)

Measurement of cerebrospinal fluid biochemical markers of Alzheimer’s disease, including but not limited to tau protein, amyloid beta peptides, or neural thread proteins, is considered experimental or investigational as there is insufficient clinical evidence to support the use of the measurement of cerebrospinal fluid biochemical markers of Alzheimer’s disease for all indications.

Measurement of urinary biochemical markers of Alzheimer’s disease, including but not limited to neural thread proteins, is considered experimental or investigational as there is insufficient clinical evidence to support the use of the measurement of urinary biochemical markers of Alzheimer’s disease for all indications.

Breast Tumor Markers

CA 15-3 (CA 27.29 or Truquant RIA) meets the definition of medical necessity for the following indications:

  • As an aid in the management of Stage II and Stage III breast cancer patients. Serial testing for CA 15-3 assay values should be used in conjunction with other clinical methods for monitoring breast cancer
  • As an aid to predict recurrent breast cancer in patients with previously treated Stage II or Stage III disease
  • As an aid in monitoring response to therapy in patients with Stage IV breast cancer. A partial or complete response to treatment will be confirmed by declining levels. A persistent rise of CA 27-29 levels despite therapy strongly suggests progressive disease.

CA 15-3 (CA 27.29 or Truquant RIA) is considered experimental or investigational, as there is insufficient clinical evidence to support the use of CA 15-3 (CA 27.29 or Truquant RIA) as a screening test for breast cancer. There is a lack of clinical data to permit conclusions on efficacy and net health outcomes.

Cancer Antigen 125 (CA-125)

CA-125 testing meets the definition of medical necessity in individuals with symptoms suggestive of ovarian cancer; symptoms may include:

  • Swelling of the abdomen (ascites)
  • Gastrointestinal symptoms (e.g., gas, bloating, long-term stomach pain, indigestion)
  • Bleeding between periods or after menopause
  • Pelvic pain
  • Feeling of pressure in the pelvis
  • Leg pain.

CA-125 testing meets the definition of medical necessity in individuals with other gynecologic malignancies, such as endometrial cancer, in whom baseline levels of CA-125 have been shown to be elevated.

CA-125 testing in asymptomatic individuals is considered experimental or investigational, as there is insufficient clinical evidence to support the use of CA-125 testing as a screening technique for ovarian cancer.

Cardiovascular Risk Panels

Cardiovascular risk panels, consisting of multiple individual biomarkers intended to assess cardiac risk (other than simple lipid panels*), are considered experimental or investigational. There is a lack of evidence as to how the panels would impact management decisions, on the clinical utility beyond simple lipid measures; and how the use of the panels would improve health outcomes.

(Cardiovascular risk panels may include: Applied Genetics Cardiac Panel; Boston Heart Advanced Risk Markers Panel; Cleveland HeartLab CVD Inflammatory Profile; Genetiks Genetic Diagnosis and Research Center Cardiovascular Risk Panel; Genova Diagnostics CV Health Plus Genomics™ Panel; Health Diagnostics Cardiac Risk Panel; Metametrix Cardiovascular Health Profile; Spectracell LPP™.)

* A simple lipid panel is generally composed of the following lipid measures:Total cholesterol; LDL cholesterol; HDL cholesterol; Triglycerides. Certain calculated ratios, such as the total/HDL cholesterol may also be reported as part of a simple lipid panel. Other types of lipid testing, i.e., apolipoproteins, lipid particle number or particle size, lipoprotein (a), etc., are not considered to be components of a simple lipid profile.

Circulating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy)

(CellSearch® System, Oncotype SEQ™, Foundation ACT, Cancer Intercept, GeneStrat®)

The use of circulating tumor DNA and circulating tumor cells is considered experimental or investigational for all indications. The cutoff levels that should be used to signal a change in member management are unknown, and there are no studies showing clinical utility and improved patient outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

Molecular Analysis for Targeted Therapy of Non-Small-Cell Lung Cancer

EGFR Gene

Analysis of mutations (point mutation in exon 21 (L858R) and small deletions in exon 19) in the gene for the epidermal growth factor receptor (EGFR) meets the definition of medical necessity as a technique to predict treatment response to an EGFR tyrosine kinase inhibitor (TKI) therapy (e.g. erlotinib [Tarceva®], gefitinib [Iressa®], or afatinib [Gilotrif®]) in members with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded (cases showing squamous cell histology).

Analysis for the T790M mutation in the gene for the EGFR receptor meets the definition of medical necessity as a technique to predict treatment response to osimertinib (Tagrisso™) in members who have progressed on or after EGFR TKI therapy.

Analysis of mutations (point mutation in exon 21 (L858R) and small deletions in exon 19) in the EGFR is considered experimental or investigational for members with advanced NSCLC of squamous cell-type. There is a lack of sufficient evidence and the predictive effects are not well defined.

Analysis for other mutations within exons 18-24, or other applications related to NSCLC, is considered experimental or investigational. There is a lack of clinical data to permit conclusions on net health outcomes.

ALK Gene

Analysis of somatic rearrangement mutations of the ALK gene meets the definition of medical necessity to predict treatment response to ALK inhibitor therapy (e.g. crizotinib [Xalkori®] or ceritinib [ZykadiaTM]) in members with advanced lung adenocarcinoma or in whom an adenocarcinoma component cannot be excluded (cases showing squamous cell histology).

Analysis of somatic rearrangement mutations of the ALK gene is considered experimental or investigational in all other situations. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Molecular Markers in Fine Needle Aspirates of the Thyroid

The use of the Afirma Gene Expression Classifier (GEC) in fine needle aspirates of the thyroid that are cytologically considered to be indeterminate (follicular lesion of undetermined significance or follicular neoplasm) meets the definition of medical necessity in members who have the following characteristics:

• Thyroid nodules without strong clinical or radiologic findings suggestive of malignancy AND

• In whom surgical decision making would be affected by test results.

Gene expression classifiers in fine needle aspirates of the thyroid not meeting criteria outlined above are considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

Mutation analysis in fine needle aspirates of the thyroid is experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

Fecal Calprotectin Testing

Fecal calprotectin testing (e.g. PhiCal™ assay) is considered experimental or investigational in the diagnosis and management of intestinal conditions, including the diagnosis and management of inflammatory bowel disease. There is insufficient evidence to permit conclusions on clinical utility or net health outcomes.

Holo-Transcobalamin

Measurement of holo-transcobalamin, including but not limited to its use in the diagnosis and management of vitamin B12 deficiency, is considered experimental or investigational, as there is insufficient clinical evidence to support the use of the measurement of holo-transcobalamin to identify early states of vitamin B12 deficiency. There are inadequate data to establish holo-TC testing as an alternative to either serum cobalamin or levels of MMA or homocysteine.

Homocysteine Testing

Measurement of plasma levels of homocysteine is considered experimental or investigational in the screening, evaluation, and management of members for cardiovascular disease. The technology is unlikely to change management or improve the net health outcome.

Measurement of plasma levels of homocysteine is considered experimental or investigational in the screening, evaluation, and management of members with venous thromboembolism or risk of venous thromboembolism. The evidence is insufficient to determine the effects of the technology on health outcomes.

Long-Chain Omega-3 Fatty Acids
in Red Blood Cell Membranes

Measurement of long chain omega-3 fatty acids in red blood cell membranes is considered experimental or investigational, as there is insufficient clinical evidence to support the use of the measurement of long chain omega-3 fatty acids as a cardiac risk factor. There is a lack of scientific evidence in the published literature regarding how measurements of red blood cell omega-3 fatty acid would affect management of individuals at risk for or patients with coronary artery disease (CAD).

Measurement of Serum Levels and Antibodies to Infliximab and Adalimumab

Measurement of antibodies to infliximab or adalimumab either alone or as a combination test which includes the measurement of serum infliximab or adalimumab levels (e.g. Prometheus® Anser™ IFX, Prometheus® Anser™ ADA), is considered experimental or investigational. There is insufficient evidence in medical literature regarding the clinical utility and impact on clinical outcomes to permit conclusions on net health outcomes.

Gene Expression-Based Assays for Cancers of Unknown Primary

Gene expression profiling is considered experimental or investigational to evaluate the site of origin of a tumor of unknown primary, or to distinguish a primary from a metastatic tumor (e.g. Pathwork Tissue of Origin®, MiRview® Mets, RosettaGX Cancer Origin (formerly miRview® mets2), ProOnc TumorSource DX™, ResponseDX: Tissue of Origin™, CancerType ID®). The data is insufficient regarding clinical utility and health outcomes.

Expanded Cancer Mutation Panels

(BioSpeciFx®, FoundationOne™, FoundationOne™ Heme, GeneKey, GeneTrails, Guardant360, Illumina TruSight, Ion AmpliSeq, MI Profile™, MI Profile™ PLUS Onclnsights™, Molecular Intelligence™ Service, OnkoMatch, Panel v2, SmartGenomics, Target Now®, TruSeq®)

The use of expanded cancer mutation panels for selecting targeting cancer treatment is considered experimental or investigational. There is limited published data available in the peer-reviewed medical literature to support the use of these tests for any indication. Additional evidence is needed to demonstrate the efficacy of the technology and the impacts on health outcomes.

Multianalyte Assays for Chronic Liver Disease

A single FibroSURE® multianalyte assay meets the definition of medical necessity for the evaluation of members with chronic liver disease.

FibroSURE® multianalyte assays are considered experimental or investigational for monitoring members with chronic liver disease.The evidence is insufficient to determine the effects of the technology on health outcomes.

The use of other multianalyte assays with algorithmic analyses (e.g. FIBROSpect® ll) is considered experimental or investigational for the evaluation or monitoring of members with chronic liver disease. The evidence is insufficient to determine the effects of the technology on health outcomes.

Multibiomarker Disease Activity Score for Rheumatoid Arthritis

The use of a multibiomarker disease activity score for rheumatoid arthritis (eg, Vectra® DA score) is considered experimental or investigational in all situations. The evidence is insufficient to determine the effects of the technology on health outcomes.

Pharmacogenomic and Metabolite Markers for Members Treated with Thiopurines

One-time genotypic analysis or phenotypic analysis of the enzyme TPMT gene meets the definition of medical necessity in members beginning therapy with azathioprine (AZA), mercaptopurine (6-MP), thioguanine, or in members on thiopurine therapy with abnormal complete blood count (CBC) results that do not respond to dose reduction.

Genotypic analysis and/or phenotypic analysis of the enzyme TPMT is considered experimental or investigational for all other indications, as there is limited clinical evidence in peer-reviewed medical literature to permit conclusions on net health outcomes.

Analysis of the metabolite markers of azathioprine (AZA) and mercaptopurine (6-MP), including 6-methyl-mercaptopurine ribonucleotides (6-MMRP) and 6-thioguanine nucleotides (6-TGN), is considered experimental or investigational. There is insufficient evidence from prospective studies on whether metabolite markers will lead to improved outcomes (primarily improved disease control and/or less adverse drug effects).

Proteogenomic Testing for Members With Cancer

(Avise SLE+, Avise SLE 2.0, Avise SLE Prognostic)

Proteogenomic testing of members with cancer (including but not limited to GPS Cancer™ test) is considered experimental or investigational for all indications. The evidence is insufficient to determine the effect of the technology on health outcomes.

Proteomic Testing for Advanced Non-Small Cell Lung Cancer (NSCLC)

Proteomic testing (VeriStrat®-Biodesix, Boulder, CO) meets the definition of medical necessity for members with advanced non-small cell lung cancer (NSCLC) meeting ALL of the following criteria:

• tumor is wild-type (no mutation detected) EGFR OR with unknown EGFR status;

• failed first-line systemic chemotherapy; AND

• test results will determine whether to proceed with erlotinib (Tarceva®) therapy.

Proteomic testing (VeriStrat) is considered experimental or investigational for all other indications. There is insufficient evidence to permit conclusions on clinical utility or net health outcomes.

Serum Biomarker Panel Testing for Systemic Lupus Erythematosus

Serum biomarker panel testing with proprietary algorithms and/or index scores for the diagnosis of systemic lupus erythematosus is considered experimental or investigational. There is uncertainty about how the use of a serum biomarker panel test for SLE would change patient management and the evidence is insufficient to determine the effects of the technology on health outcomes.

Serum Biomarker Tests for
Multiple Sclerosis

Serum biomarker tests (e.g. gMS® Dx, gMS® Pro EDSS) for multiple sclerosis are considered experimental or investigational for all indications. There is insufficient evidence from prospective studies demonstrating improved health outcomes in individuals who may have multiple sclerosis and who are treated according to test results.

Uveal Melanoma

Gene expression profiling for uveal melanoma with DecisionDx-UM meets the definition of medical necessity for members with primary, localized uveal melanoma.

Gene expression profiling for uveal melanoma that do not meet the above criteria is considered experimental or investigational. The evidence is insufficient to determine the effects of the technology on health outcomes.

The following tumor markers are considered experimental or investigational for all indications, as there is insufficient evidence in the peer reviewed medical literature to support the use of these markers for screening, diagnosing, staging, surveillance or monitoring response to treatment:

Table 1

a2-PAG

pregnancy-associated alpha-2-glycoprotein

BCM

breast cancer mucin

CA50

cancer antigen 50

CA72-4

cancer antigen 72-4

CA195

cancer antigen 195

CA242

cancer antigen 242

CA549

carbohydrate antigen/cancer antigen 594

CA-SCC

squamous cell carcinoma antigen

CAM17-1

monocolonal antimucin antibody 17-1

CAM-26

monocolonal antimucin antibody 26

CAM-29

monocolonal antimucin antibody 29

CAR-3

antigenic determinant recognized by monoclonal antibody AR-3

DU-PAN-2

sialylated carbohydrate antigen DU-PAN-2

MCA

mucin-like carcinoma-associated antigen

NSE

neuron-specific enolase

P-LAP

placental alkaline phosphatase

PNA/ELLA

peanut lectin bonding assay

SLEX

sialylated Lewis X-I antigen

SLX

sialylated SSEA-1 antigen

SPAN-1

sialylated carbohydrate antigen SPAN-1

ST-439

sialylated carbohydrate antigen ST-439

TAG12

tumor-associated glycoprotein 12

TAG72

tumor-associated glycoprotein 72

TAG72.3

tumor-associated glycoprotein 72.3

TATI

tumor-associated trypsin inhibitor

TNF-a

tumor necrosis factor alpha

TPA

tissue polypeptic antigen

The following tests are considered experimental or investigational, as there is insufficient evidence to support the use of these tests for all indications. Although there are ongoing clinical studies the current data are inadequate to permit scientific conclusions regarding the impact on management decisions and net health outcomes.

BILLING/CODING INFORMATION:

Afirma® Gene Expression Classifier

CPT Coding

81545

Oncology (thyroid), gene expression analysis of 142 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (eg, benign or suspicious)

ICD-10 Diagnoses Codes That Support Medical Necessity (81545)

C73

Malignant neoplasm of thyroid gland

D44.0

Neoplasm of uncertain behavior of thyroid gland

Biochemical Markers of Alzheimer’s Disease

There are no specific CPT or HCPCS codes describing measurement of biochemical markers of Alzheimer’s disease.

Breast Tumor Markers

CPT Coding

86300

Immunoassay for tumor antigen, Quantitative; CA 15-3 (27.29)

ICD-10 Diagnoses Codes That Support Medical Necessity (86300)

C50.011 – C50.929

Malignant neoplasm of breast

C79.2

Secondary malignant neoplasm of skin

C79.81

Secondary malignant neoplasm of breast

G89.3

Neoplasm related pain (acute) (chronic)

R97.8

Other abnormal tumor markers

Z85.3

Personal history of malignant neoplasm of breast

Cancer Antigen 125 (CA-125)

CPT Coding

86304

Immunoassay for tumor antigen, CA-125

ICD-10 Diagnoses Codes That Support Medical Necessity (86304)

C45.1

Mesothelioma of peritoneum

C48.1

Malignant neoplasm of specified parts of peritoneum

C48.2

Malignant neoplasm of peritoneum, unspecified

C48.8

Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

C53.0

Malignant neoplasm of endocervix

C53.1

Malignant neoplasm of exocervix

C54.1 – C54.9

Malignant neoplasm of corpus uteri

C56.1 – C56.9

Malignant neoplasm of ovary

C57.00 – C57.9

Malignant neoplasm of other and unspecified female genital organs

C79.60

Secondary malignant neoplasm of ovary, unspecified side

C79.61

Secondary malignant neoplasm of right ovary

C79.62

Secondary malignant neoplasm of left ovary

C79.82

Secondary malignant neoplasm of genital organs

C79.89

Secondary malignant neoplasm of other specified sites

D39.0
D39.10 – D39.12
D39.7 – D39.9

Neoplasm of uncertain behavior of female genital organs

G89.3

Neoplasm related pain (acute) (chronic)

R19.00

Intra-abdominal and pelvic swelling, mass and lump, unspecified site

R19.01

Right upper quadrant abdominal swelling, mass and lump

R19.02

Left upper quadrant abdominal swelling, mass and lump

R19.03

Right lower quadrant abdominal swelling, mass and lump

R19.04

Left lower quadrant abdominal swelling, mass and lump

R19.05

Periumbilical swelling, mass or lump

R19.06

Epigastric swelling, mass or lump

R19.07

Generalized intra-abdominal and pelvic swelling, mass and lump

R19.09

Other intra-abdominal and pelvic swelling, mass and lump

R97.1

Elevated cancer antigen 125 [CA 125]

R97.8

Other abnormal tumor markers

Z85.40

Personal history of malignant neoplasm of unspecified female genital organ

Z85.41

Personal history of malignant neoplasm of cervix uteri

Z85.42

Personal history of malignant neoplasm of other parts of uterus

Z85.43

Personal history of malignant neoplasm of ovary

Z85.44

Personal history of malignant neoplasm of other female genital organs

CancerType ID®

CPT Coding

81540

Oncology (tumor of unknown origin), mRNA, gene expression profiling by real-time RT-PCR of 92 genes (87 content and 5 housekeeping) to classify tumor into main cancer type and subtype, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a probability of a predicted main cancer type and subtype (investigational)

Epidermal Growth Factor Receptor (EGFR) Analysis

CPT Coding

81235

EGFR (epidermal growth factor receptor) (e.g., non-small cell lung cancer) gene analysis, common variants (e.g., exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q)

Expanded Cancer Mutation Panels

81445

81445 Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, NRAS, MET, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed (Investigational)

81450

Targeted genomic sequence analysis panel, hematolymphoid neoplasm or disorder, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, BRAF, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KRAS, KIT, MLL, NRAS, NPM1, NOTCH1), interrogation for sequence variants, and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed (Investigational)

81455

Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm, DNA analysis, and RNA analysis when performed, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MLL, NPM1, NRAS, MET, NOTCH1, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed (Investigational)

Fecal Calprotectin Testing

CPT Coding

83993

Calprotectin, fecal (investigational)

Homocysteine Testing

CPT Coding

83090

Homocysteine (investigational)

InflammaDry®

InflammaDry® may be reported with CPT code 83516-Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; qualitative or semiquantitative, multiple step method.

Long-Chain Omega-3 Fatty Acids in Red Blood Cell Membranes

CPT Coding

0111T

Long chain (C20-22) omega-3 fatty acids in red blood cell (RBC) membranes (investigational)

Pharmacogenomic and Metabolite Markers for Members Treated with Thiopurines

The analysis of common variants of the TPMT gene may be reported with CPT code 81401 – Molecular pathology procedure, Level 2 (e.g., 2-10 single nucleotide polymorphisms [SNPs], 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat).

There are no specific CPT codes for metabolite markers of AZA, 6-MP or thioguanine.

There is a CPT genetic testing modifier that is specific to TPMT: -9A: TPMT, commonly called thiopurine methyltransferase (patients on antimetabolite therapy).

Circulating Tumor Cells/Liquid Biopsy (CellSearch)

CPT Coding

86152

Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood) (investigational)

86153

Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); physician interpretation and report, when required (investigational)

0009U

Oncology (breast cancer), ERBB2 (HER2) copy number by FISH, tumor cells from formalin fixed paraffin embedded tissue isolated using image-based dielectrophoresis (DEP) sorting, reported as ERBB2 gene amplified or non-amplified (investigational)

OVA1®

CPT Coding

81503

Oncology (ovarian), biochemical assays of five proteins (CA-125, apoliproprotein A1, beta-2 microglobulin, transferrin and pre-albumin), utilizing serum, algorithm reported as a risk score (investigational)

Overa®

CPT Coding

0003U

Oncology (ovarian) biochemical assays of five proteins (apolipoprotein A-1, CA 125 II, follicle stimulating hormone, human epididymis protein 4, transferrin), utilizing serum, algorithm reported as a likelihood score (investigational)

HE4 immunoassay

CPT Coding

86305

Human epididymis protein 4 (HE4) (investigational)

Multianalyte Assays for Chronic Liver Disease (FibroSURE® tests)

CPT Coding

0001M

Infectious disease, HCV, six biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, and haptoglobin) utilizing serum, prognostic algorithm reported as scores for fibrosis and necroinflammatory activity in liver

0002M

Liver disease, ten biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, haptoglobin, AST, glucose, total cholesterol and triglycerides) utilizing serum, prognostic algorithm reported as quantitative scores for fibrosis, steatosis and alcoholic steatohepatitis (ASH)

0003M

Liver disease, ten biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, total bilirubin, GGT, haptoglobin, AST, glucose, total cholesterol and triglycerides) utilizing serum, prognostic algorithm reported as quantitative scores for fibrosis, steatosis and nonalcoholic steatohepatitis (NASH)

NETest

CPT Coding

0007M

Oncology (gastrointestinal neuroendocrine tumors), real-time PCR expression analysis of 51 genes, utilizing whole peripheral blood, algorithm reported as a nomogram of tumor disease index (investigational)

Pathwork Tissue of Origin®

CPT Coding

81504

Oncology (tissue of origin), microarray gene expression profiling of > 2000 genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as tissue similarity scores (investigational)

PreDx Diabetes Risk Score™

CPT Coding

81506

Endocrinology (type 2 diabetes), biochemical assays of seven analytes (glucose, HbA1c, insulin, hs-CRP, adoponectin, ferritin, interleukin 2-receptor alpha), utilizing serum or plasma, algorithm reporting a risk score (investigational)

ROMA™

CPT Coding

81500

Oncology (ovarian), biochemical assays of two proteins (CA-125 and HE4), utilizing serum, with menopausal status, algorithm reported as a risk score (investigational)

86316**

Immunoassay for tumor antigen; other antigen, quantitative (e.g., CA 50, 72-4, 549), each (investigational)

**May be covered when meets the definition of medical necessity when used to report the Chromogranin A (CgA) test for neuroendocrine tumors (i.e. carcinoid tumors).

Vectra®DA

CPT Coding

81490

Autoimmune (rheumatoid arthritis), analysis of 12 biomarkers using immunoassays, utilizing serum, prognostic algorithm reported as a disease activity score (investigational)

VeriStrat®

CPT Coding

81538

Oncology (lung), mass spectrometric 8-protein signature, including amyloid A, utilizing serum, prognostic and predictive algorithm reported as good versus poor overall survival

ICD-10 Diagnoses Codes That Support Medical Necessity (81538)

C34.00

Malignant neoplasm of unspecified main bronchus

C34.01

Malignant neoplasm of right main bronchus

C34.02

Malignant neoplasm of left main bronchus

C34.10

Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.11

Malignant neoplasm of upper lobe, right bronchus or lung

C34.12

Malignant neoplasm of upper lobe, left bronchus or lung

C34.2

Malignant neoplasm of middle lobe, bronchus or lung

C34.30

Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.31

Malignant neoplasm of lower lobe, right bronchus or lung

C34.32

Malignant neoplasm of lower lobe, left bronchus or lung

C34.80

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.81

Malignant neoplasm of overlapping sites of right bronchus and lung

C34.82

Malignant neoplasm of overlapping sites of left bronchus and lung

C34.90

Malignant neoplasm of unspecified part of unspecified bronchus or lung

C34.91

Malignant neoplasm of unspecified part of right bronchus or lung

C34.92

Malignant neoplasm of unspecified part of left bronchus or lung

xTAG® Gastrointestinal Pathogen Panel (GPP)

CPT Coding

87505

Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (e.g., Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 3-5 targets (investigational)

87506

Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (e.g., Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and multiplex amplified probe technique, multiple types or subtypes, 6‐11 targets (investigational)

87507

Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen (e.g., Clostridium difficile, E. coli, Salmonella, Shigella, norovirus, Giardia), includes multiplex reverse transcription, when performed, and Multiplex amplified probe technique, multiple types or subtypes, 12‐25 targets (investigational)

Tumor markers that do not have a specific CPT or HCPCS code may be reported with a nonspecific code such as CPT code 86316.

REIMBURSEMENT INFORMATION:

Breast Tumor Markers

Reimbursement for CA 15-3 (CA 27.29 or Truquant RIA) (86300) is limited to twelve (12) tumor markers within a twelve (12) month period. Additional CA 15-3 (CA 27.29 or Truquant RIA) (86300) is subject to medical review for determination of medical necessity (e.g., clinical indications indicate additional tumor markers contribute to improved health outcomes or alters treatment and/or management).

During chemotherapy, the usual frequency for monitoring CA 15-3 (CA 27.29 or Truquant RIA) is once (1) every three (3) weeks to coincide with the chemotherapy cycles (usually 6 to 12 months). If there is clinical indication(s) of progression during the course of chemotherapy, a CA 15-3 (CA 27.29 or Truquant RIA) may be performed between cycles, up to a weekly interval. Patients who have completed chemotherapy generally have a monthly test for the first three (3) months, then every three (3) months afterwards. As the patient approaches a five (5) year disease free status, the frequency is reduced to every six (6) months. Patients who are at low risk for recurrence (Stage I and selected Stage II) may be tested at three (3) month intervals, even during the period immediately following chemotherapy.

Cancer Antigen 125 (CA-125)

Reimbursement for CA-125 (86304) is limited to twelve (12) tumor markers within a twelve (12) month period. Additional tumor markers (86304) are subject to medical review for determination of medical necessity (e.g., clinical indications indicate additional tumor markers contribute to improved health outcomes or alter treatment or management).

The following information is required documentation to support medical necessity: physician history and physical, physician progress notes, laboratory studies, treatment plan, and physician operative report (if applicable).

LOINC Codes

Documentation Table

LOINC Codes

LOINC Time Frame Modifier Code

LOINC Time Frame Modifier Codes Narrative

Physician history and physical

28626-0

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

Attending physician progress note

18741-9

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Plan of treatment

18776-5

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Laboratory studies

26436-6

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

Physician operative report

28573-4

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products:

The following National Coverage Determination (NCD) located at www.cms.gov was reviewed on the last guideline reviewed date: Tumor Antigen by Immunoassay-CA19-9 (190.30)

The following Local Coverage Determination (LCD) located at www.fcso.com was reviewed on the last guideline reviewed date:Noncovered Services (L33777)

The following were reviewed on the last guideline reviewed date and are located at palmettogba.com:

• MolDX: Afirma Assay by Veracyte Coding and Billing Guidelines (M00015)

• MolDX: Approved Gene Testing (M00041,V16)

• MolDX: Pathwork Tissue of Origin Test Coding and Billing Guidelines

• MolDX: Vectra DA Coding and Billing Guidelines (M00031),

The following located at novitas-solutions.com was reviewed on the last guideline reviewed date:

• Local Coverage Article: miRview mets 2 - Provider Bulletin (A51919)

• Local Coverage Determination (LCD): Biomarkers for Oncology (L35396).

DEFINITIONS:

A2-PAG: pregnancy-associated alpha-2 glycoprotein (a chemical made by some cancers, consisting of a combination of protein and sugars).

BCM: breast cancer mucin; a marker made by some breast cancers.

CAM17-1, CAM26, CAM29: also known as monoclonal anti-mucin antibody markers, are markers noted in certain cancers.

CAR-3: a marker that reacts with a special test using a specific protein testing substance called “monoclonal antibody AR-3”.

Carbohydrate cancer antigens: CA 19-9, CA-125, CA 15-3/CA27-23, CA 242, CA 50, CA 72-4, CA 195, CA 549, M26, M29: these and other markers are a way to test for special markers on tumors, that are made of carbohydrates (a chemical that resembles a type of sugar).

CgA: a major protein of the granin family that has been described as a potential marker for neuroendrocrine tumors.

CellSearch®: a serum-based test that measures circulating tumor cells.

DU-PAN-2: a chemical (sialylated carbohydrate antigen) that may be found with some cancers.

FibroSpect II: serum marker panels for the diagnosis or clinical management of liver disease.

FibroSure: serum marker panels for the diagnosis or clinical management of liver disease.

GeneSearch BLN: an assay for the detection of greater than 0.2mm metastases in nodal tissue removed from sentinel lymph node biopsies of breast cancer patients.

HE4: an enzyme immunoassay for the quantitative determination of Human Epididymis Protein 4 (HE4) antigen in ovarian cancer.

LPA: lysophosphatidic acid; a chemical that has bee suggested as a possible test for ovarian cancer, body levels may be high in other cancers as well.

MCA: a chemical (Mucin-like Carcinoma-associated Antigen) that may be found in breast cancers.

MSA: a chemical (Mammary Serum Antigen) that may be found in breast cancers.

NSE: Neuron-Specific Enolase, a chemical made in the presence of some cancers.

Ova Check™: a serum-based test for the early detection of epithelial ovarian cancer.

OvaSure™: ovarian cancer-screening test that may be able to assess the presence of early stage ovarian cancer in high-risk woman.

Pathwork Tissue of Origin: a diagnostic test that may aid in the diagnosis of tumors with uncertain origins.

P-LAP: placental alkaline phosphatase, a chemical made in the presence of some cancers.

PNA/ELLA: peanut lectin bonding assay, a test for a certain tumor marker.

Proteogenomic Testing: involves the integration of proteomic, transcriptomic, and genomic information.

Proteomic Testing: the measurement of protein products alone, without integration of genomic and transcriptomic information.

SLEX, SLX: sialylated Lewis X-I antigen and sialylated SSEA-1 antigen.

SPAN-1: a sialylated carbohydrate antigen.

ST-439: a sialylated carbohydrate antigen.

TAG12, TAG 72, TAG 72.3: tumor associated glycoproteins; chemicals made by some cancers, consisting of a combination of protein and sugars.

TATI: tumor-associated trypsin inhibitor, a chemical made by the body, in the presence of some cancers.

TNF-a: tumor necrosis factor alpha, a chemical made by the immune system in the presence of some cancers.

TPA: tissue polypeptide antigen is a marker that may be present on some cancers.

RELATED GUIDELINES:

Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer, 05-86000-26
Genetic Testing, 05-82000-28

KRAS, NRAS, and BRAF Mutation Analysis in Metastatic Colorectal Cancer, 05-86000-28

PathFinderTG® Molecular Testing, 05-86000-27

OTHER:

None applicable.

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COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the Florida Blue Medical Policy & Coverage Committee on 03/23/17.

GUIDELINE UPDATE INFORMATION:

02/15/04

Developed separate guideline for non-covered tumor markers from the Tumor Markers guideline. Added program exception and added diagnoses [155.1, 156.1, 156.8, 156.9, 157.0 – 157.9, 197.8, 235.3, 235.5, V10.09] for 86301 for Medicare & More.

02/15/05

Deleted CA 19-9 from the investigational statement. Deleted Medicare program exception. Deleted the following from the when services are covered section of the MCG (per MPCC recommendation): Non-covered/investigational serum tumor markers may be covered if the individual subscriber has a benefit to cover non-covered/investigational services (refer to contract benefits). Updated related guidelines section.

08/15/07

Review, investigational status maintained, guideline reformatted, references updated.

09/15/08

Annual review: Position statements maintained. Description section and references updated.

08/15/09

Annual review: Guideline title changed, position statements updated, position statements from other tumor marker guidelines incorporated, description section, coding and references updated.

12/15/09

Updated the list of experimental/investigational tests.

01/01/10

Annual HCPCS coding update: added code 86305.

04/15/10

Updated the list of experimental/investigational tests and the Medicare Advantage program exception.

11/15/10

Revision; updated the list of experimental/investigational tests and added related ICD-10 codes.

08/15/11

Revision; Medicare Advantage and references updated; formatting changes.

01/01/12

Annual HCPCS update. Added CPT codes 0279T, 0280T.

04/01/12

Quarterly HCPCS update. Deleted HCPCS code S3711.

08/24/12

Reimbursement section updated.

10/15/12

Serum Antibodies for the Diagnosis of Inflammatory Bowel Disease position statement removed and added to the Genetic Testing guideline; reimbursement section updated.

11/15/12

List of experimental/investigational tests updated.

01/01/13

Annual HCPCS update. Added codes 81500, 81503, 81506, 86152, 86153, 0001M-0003M; deleted codes 0279T & 0280T.Updated position statement section and references.

02/15/13

Revision; position statement section and references updated.

03/15/13

Revision; position statement section including the list of investigational tests and references updated; title change.

05/15/13

Revision; position statement, billing/coding, program exception, and reference sections updated.

09/15/13

Revision; position statement section and references updated.

01/01/14

Annual HCPCS update. Added code 81504.

02/15/14

Revision; position statement section, Medicare program exception, and references updated.

06/15/14

Revision; position statement section, Coding, Medicare program exception, and references updated.

07/01/14

Quarterly HCPCS update. Added code 0007M.

10/15/14

Revision;Update the position statement and coding sections, program exception, and references.

01/01/15

Annual HCPCS/CPT update. Added codes 87505-87507.

06/15/15

Revision; position statement section, billing/coding, and references updated.

11/01/15

Revision: ICD-9 Codes deleted.

11/15/15

Revision; program exception and references updated.

01/01/16

Annual HCPCS/CPT update; codes 81490, 81538, 81540, 81545 added, code 0103T deleted.

01/01/16

Annual HCPCS/CPT update; codes 81490, 81538, 81540, 81545 added, code 0103T deleted.

03/15/16

Revision; position statement section, codeing and references updated.

09/15/16

Revision; position statement section, program exception, and references updated.

11/15/16

Revision; position statement section and references updated.

12/15/16

Revision; position statement, coding, and references updated.

02/01/17

Coding Update; new code 0003U added; investigational test list updated.

02/15/17

Revision; position statements, coding, and references updated.

03/15/17

Revision; Multianalyte assays for chronic liver disease position statements revised; coding and references updated.

04/15/17

Revision; Uveal Melanoma position statement added and references updated.

06/15/17

Revision; test names added to Biochemical Markers of Alzheimer’s Disease & Circulating Tumor DNA position statements section; investigational test list updated.

07/15/17

Revision; Investigational test list updated.

08/01/17

Coding update; Added code 0009U.

Date Printed: August 18, 2017: 10:21 AM