Medical Policy: 02.01.20 

Original Effective Date: December 2000 

Reviewed: August 2017 

Revised: August 2017 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Tumor markers are substances normally produced by cancer or other cells in the body in response to cancer, or certain benign conditions. Most tumor markers are proteins but may also be patterns of gene expression and changes to DNA. Tumor markers are made by normal cells but are produced at a much higher level in the presence of cancer. Tumor markers may be found in the blood, plasma, other bodily fluids (e.g., urine, saliva, cerebrospinal fluid) and/or tissue. Although an abnormal tumor marker level may suggest cancer, their presence alone does not confirm a diagnosis. Tumor makers are typically combined with other diagnostic studies (e.g. laboratory tests, biopsy, radiological imaging) to confirm the diagnosis. These markers may not be elevated in the presence of some diseases or cancers, especially in early stages of the disease, they may not be specific to a particular type of disease or cancer, and/or they may be elevated by more than one type of disease or cancer. 

 

In some types of cancers, tumor marker levels may reflect the extent or stage of the disease and can be useful in determining the most effective treatment and how the disease will respond to the treatment. Typically, the primary use of tumor markers is to monitor a cancer’s response to treatment with periodic measurements following therapy. Following therapy, a decrease in the maker level may indicate a response to therapy as opposed to consistently elevated or rising marker levels which may be indicative of lack of response to treatment or recurrence of the disease. The evidence in the published peer reviewed literature and professional societies support tumor markers for the diagnosis and management of some cancers, while other tumor markers are still evolving and their clinical utility has not been proven.

Summary

Recommendations and guidelines by professional societies and organizations and evidence in the published peer reviewed scientific literature support the use of defined tumor markers for the diagnosis, treatment planning, treatment monitoring and/or follow up of specific cancers.

 

However, improvements in meaningful health outcomes for numerous other tumor markers have not been proven and they are still under investigation to determine their clinical utility in the management of individuals with various types of cancers. Overall, clinical trials have primarily been in the form of retrospective validation studies with small heterogeneous patient populations and short term follow ups. Studies comparing the tumor markers to established treatment options are lacking and management of patients based on the results of these markers have not been published.

Practice Guidelines and Position Statements

The American College of Obstetricians and Gynecologists (ACOG)

In 2011, the American College of Obstetricians and Gynecologists (ACOG), issued a committee opinion Number 477, role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer which included the following recommendations:

  • Epithelial ovarian cancer is most commonly detected in advanced stage, when the overall 5 year survival rate is 20%-30%.
  • Detection of early stage ovarian cancer results in improved survival.
  • There is currently no effective strategy for ovarian cancer screening.
  • The obstetrician-gynecologist should be aware that there may be symptoms (including increased abdominal size or bloating, abdominal or pelvic pain, or feeling full quickly or difficulty eating) associated with ovarian cancer that should be investigated.
  • Evaluation of the symptomatic patient includes physical examination and may include transvaginal ultrasonography and measurement of levels of the serum tumor marker CA-125.
  • When a patient with a suspicious or persistent complex adnexal mass requires surgical evaluation, a physician trained to appropriately stage and debulk ovarian cancer, such as a gynecologist oncologist, should perform the operation

 

American Society of Clinical Oncology (ASCO) 

Breast Cancer

In 2007, the American Society of Clinical Oncology (ASCO) issued an update of recommendations for the use of tumor markers in breast cancer that included the following:

 

Recommendations for use of tumor markers in breast cancer:

  • CA 15-3 and CA 27.29:
    • Present data is insufficient to recommend CA 15-3 or CA 27.29 for screening, diagnosis and staging.
    • Present data does not support the use of CA 15-3 or CA 27.29 for monitoring patients for recurrence after primary breast cancer therapy. 
    • CA 15-3 and CA 27.29 to contribute to decisions regarding therapy for metastatic breast cancer. For monitoring patients with metastatic disease during active therapy, CA 27.29 or CA 15-3 can be used in conjunction with the patient’s history and physical examination, and diagnostic imaging.
    • Present data is insufficient to recommend the use of CA 15-3 or CA 27.29 alone for monitoring response to treatment. However, in the absence of readily measurable disease, an increasing CA 15-3 or CA 27.29 may be used to indicate treatment failure. Caution should be used when interpreting a rising CA 27.29 or CA 15-3 level during the first 4-6 weeks of new therapy, since spurious early rises may occur.
  • CEA:
    • CEA is not recommended for screening, diagnosis, staging or routine surveillance of breast cancer patients after primary therapy
    • CEA to contribute to decisions regarding therapy for metastatic breast cancer. For monitoring patients with metastatic disease during active therapy, CEA can be used in conjunction with history and physical examination, and a diagnostic imaging. Present data is insufficient to recommend the use of CEA for monitoring response to treatment. However, in the absence of readily measurable disease, an increasing CEA may be used to indicate treatment failure. Caution should be used when interpreting a rising CEA level during the first 4-6 weeks of new therapy, since spurious early rises may occur.

In 2012, the American Society of Clinical Oncology (ASCO) issued a clinical practice update on breast cancer follow-up and management after primary treatment which included the following recommendation:

 

Recommendation for Breast Cancer Follow-Up and Management in Adjuvant Setting: Not Recommended:

  • The use of CA 15-3 or CA 27.29 is not recommended for routine surveillance of patients with breast cancer after primary therapy.
  • CEA testing is not recommended for routine surveillance of patients with breast cancer after primary therapy.

In 2015, the American Society of Clinical Oncology (ASCO) a clinical practive guideline, use of biomarkers to guide decisions on systemic therapy for women with metasatic breast cancer, to include the following recommendation:

  • CEA, CA 15-3 and CA 27.29 may be used as adjuvant assessments to contribute to decisions regarding therapy for metastatic breast cancer. Data are insufficient to recommend use of CEA, CA 15-3, and CA 27-29 alone for monitoring response to treatment. The recommendations for use is based on clinical experience and Panel informal consensus in the absence of studies designed to evaluate the clinical utility of markers. As such, it is also reasonable for clinicians to not use these markers as adjunctive assessments. (Type: informal consensus. Evidence quality: insufficient. Strength of recommendation: moderate)

 

Gastrointestinal Cancers (Colorectal cancer and Pancreatic Cancer)
In 2006, the American Society of Clinical Oncology (ASCO) issued an update recommendation for the use of tumor markers in gastrointestinal cancer, which included the following recommendations:

 

Tumor Marker Recommendations for Colorectal Cancer

Tumor Marker Screening Staging/Treatment Planning Postoperative Monitoring Response to Therapy
CEA

No: CEA is not recommended as a screening testing for colorectal cancer

Yes: CEA may be ordered preoperative in patients with colorectal carcinoma it it would assist in surgical treatment planning and staging; data is insufficient to support the use of CEA to determine whether to treat a patient with adjuvant therapy

Yes: Postoperative serum CEA testing should be performed every three months in patients with stage II or III disease for at least three years after diagnosis, if the patient is a condidate for surgery or systemic therapy

 

Note: Because chemotherapy may falsely elevate CEA levels, waiting until chemotherapy is finished to initiate surveillance is advised.

Yes, CEA should be measured at the start of treatment for metastatic disease and every one to three months during treatment

CA 19-9

No: Present data are insufficient to recommend CA 19-9 for screening, diagnosis, staging, surveillance or monitoring treatment of patients with colorectal cancer

No: Present data are insufficient to recommend CA 19-9 for staging patients with colorectal cancer

No: Present data are insufficient to recommend surveillance or monitoring of treatment of patients with colorectal cancer

No: Present data are insufficient to recommend surveillance or monitoring of treatment with patients with colorectal cancer

 

Tumor Marker Recommendations for Pancreatic Cancer

Tumor Marker Screening Operability Evidence of RecurrenceMonitoring Response to Therapy 
CA 19-9

No: CA 19-9 is not recommended for use as a screening test for pancreatic cancer

No: The use of CA 19-9 testing alone is not recommended for use in determining operability or the results of operability in pancreatic cancer

Evidence of recurrence: CA 19-9 determinations by themselves cannot provide definitive evidence of disease recurrence without seeking confirmation with imaging studies for clinical findings and/or biopsy

Monitoring response to therapy: Present data are insufficient to recommend the routine use of serum CA 19-9 rules alone for monitoring response to treatment. However, CA 19-9 can be measured at the start of treatment for locally advanced metastatic disease and every 1 to 3 months during active treatment.  If there is an elevation in serial CA 19-9 determinations, this may be an indication of progressive disease and confirmation with other studies should be sought.

 

National Comprehensive Cancer Network (NCCN) 

Breast Cancer Version 2.2017
Principles of Monitoring Metastatic Disease Findings Concerning for Progression of Disease Include Serum Tumor Markers (CEA, CA 15-3, CA 27.29)
Baseline Prior to New Therapy Chemotherapy Endocrine Therapy Restaging if Concern for Progression of Disease
Optional Optional Optional Optional

 

Colon Cancer Version 2.2017

Serum Tumor Marker (CEA)

 

Rectal Cancer Version 3.2017

Serum Tumor Marker (CEA)

 

BRCA-Related Breast and/or Ovarian Cancer Syndrome Version 2.2017

Serum Tumor Marker (CA-125)

 

Ovarian Cancer Version 2.2017
Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

Serum Tumor Marker (CA-125 and CEA)

 

Ovarian Cancer Version 2.2017
Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer
Serum Tumor Marker Surveillance for Malignant Germ Cell and Sex Cord Stromal Tumors

(Serum Tumor Marker CA-125)

Germ Cell Tumors
<1 Year Years 1-2 Years 2-3 Years 3-5 >5 years

Every 2-4 months

Every 2-4 months

Not indicated

Not indicated

Not indicated

Sex Cord Stromal Tumors
<1 Year Years 1-2 Years 2-3 Years 3-5 >5 years

Every 2-4 months

Every 2-4 months

Every 6 months

Every 6 months

Every 6 months

Recurrence Suspected: For germ cell tumors and sex cord stromal tumors – CA - 125

 

Uterine Neoplasms Version 3.2017

Endometrial Carcinoma and Serum Tumor Marker CA-125

 

Pancreatic Adenocarcinoma Version 2.2017 

Serum Tumor Marker (CA 19-9)  

 

Hepatobiliary Cancers Version 3.2017

Serum Tumor Markers (CEA and CA 19-9)

 

Occult Primary Version 2.2016
Adenocarcinoma or Carcinoma not Otherwise Specified

Serum Tumor Markers (CA-125 and CA 19-9)

 

Thyroid Carcinoma Version 2.2017
Medullary Carcinoma

Serum Tumor Marker (CEA)

Neuroendocrine Tumors Version 3.2017

Serum Tumor Markers (Chromogranin A (CgA) and 24 Hour Urine 5-HIAA)

 

Soft Tissue Sarcoma Version 2.2017

Gastrointestinal Stromal Tumors (GIST) Serum Tumor Marker (KIT)

 

Acute Myeloid Leukemia Version 3.2017

Serum Tumor Marker (KIT)

Non-Small Cell Lung Cancer Version 8.2017 

Serum Tumor Markers (CEA)  

 

Prior Approval:

 

Not applicable

 

Policy:

  • See medical policy 02.04.65 Molecular Markers in Fine Needle Aspirates of the Thyroid
  • See medical policy 02.04.45 Proteomics Based Testing for Evaluation of Ovarian Cancer
  • See medical policy 02.04.59 Gene Expression Profiling for the Management of Breast Cancer

 

 

The following serum tumor markers are considered medically necessary for the diagnosis and management of the specific condition(s) indicated below:
Note: See information above in the Description section regarding when tumor markers should be performed. 

Tumor Marker Condition(s)

Carcinoembryonic Antigen (CEA)(82378)

  • Metastatic Breast Cancer
  • Colorectal Cancer
  • Hepatobilliary Cancers including:
    • Intrahepatic Cholangiocarcionoma
    • Extrahepatic Cholangiocarcinoma
    • Gallbladder Cancer
  • Medullary Thyroid Carcinoma
  • Pseudomyxoma peritonei/mucinous carcinoma of the ovary
  • Lung cancer 

Cancer Antigen 125      

(CA-125)
(86304)

  • Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
  • Ovarian low malignant potential tumors (borderline epithelial ovarian tumors) 
  • BRCA mutation positive management related to the risk of developing ovarian cancer in patients who have not elected risk reducing salpingo-oopherectomy (RRSO), may be considered as an additional screening test at the clinician’s discretion starting at age 30-35 years
  • Undiagnosed pelvic mass: less common ovarian histopathologies (malignant germ cell neoplasms; carcinosarcoma (MMMT); malignant sex cord stromal tumors
  • Endometrial cancer: suspected extrauterine disease (endometrioid histologies)
  • Occult primary cancer of unknown primary adenocarcinoma to rule out ovarian cancer 
CA 19-9
(86301)
  • Pancreatic Cancer
  • Hepatobilliary Cancers including:
    • Intrahepatic Cholangiocarcionoma
    • Extrahepatic Cholangiocarcinoma
    • Gallbladder Cancer
  • To aid in the detection of cholangiocarcinoma in patients with primary sclerosing cholangitis
  • Occult Primary Cancer of Unknown Primary – Adenocarcinoma or Carcinoma not otherwise specified
    • Peritoneal/Ascites – if pancreatic or biliary tract primary suspected
    • Liver – if pancreatic or biliary tract primary suspected
  • Pseudomyxoma peritonei

CA 15-3 and CA 27.29
(86300)

  •  Metastatic Breast Cancer

5-HIAA (5 Hydrocyindoleascetic Acid) (24 hour urine) (83497)

  • Neuroendocrine Tumors

Chromogranin A (CgA) (86316)

  • Neuroendocrine Tumors 

KIT (81272)

  • Acute Myeloid Leukemia
  • Gastrointestinal stromal tumors (GIST)

  

Any of the tumor markers listed above for any cancer indication not otherwise listed and all other applications of serum tumor markers are considered investigational including but not limited to the following:

  • Ova-1 (CA-125, apolipoprotein A1, beta 2 microglobulin transferin and pre-albumin) and ROMA (CA-125 and HE4
  • Human epididymis protein (HE4)
  • A2-PAG (pregnancy associated alpha2 glycoprotein)
  • BCM (breast cancer mucin)
  • CAM 17-1 (antimucin monoclonal antibody)
  • CAM-26 (carcinoma associated mucin antigen)
  • CAM-29 (carcinoma associated mucin antigen)
  • MCA (mucinous carcinoma associated antigen)
  • TPA (tissue polypeptide antigen)
  • TPS (tissue polypeptide specific antigen)
  • CA 72-4 (cancer antigen 72-4)
  • CA-50 (cancer antigen 50)
  • CA-242 (cancer antigen 242)
  • CA-195 (cancer antigen 195)
  • CA-549 (cancer antigen 549)
  • CA-SCC (squamous cell carcinoma antigen)
  • CAR-3 (antigenic determinant recognized by monoclonal antibody AR-3)
  • DMSA (pentavalent technetium-99mm dimercaptosuccinic acid)
  • NSE (neuron specific enolase)
  • Du-PAN-2 (sialylated carbohydrate antigen)
  • EPCA-2 (early prostate cancer antigen)
  • TAG-12 (tumor associated glycoprotein 12)
  • TAG 72 (tumor associated glycoprotein 72)
  • TAG-72-3 (tumor associated glycoprotein 72-3)
  • TNF-alpha (TNF-a) (tumor necrosis factor alpha)
  • TATI (tumor associated trypsin inhibitor)
  • P-LAP (placental alkaline phosphatase)
  • PNA-ELLA (peanut lectin bonding assay)
  • P53 (monocolonal antibody)
  • SLEX (sialylated Lewis-X antigen)
  • SLX (sialylated SSEA-1 antigen)
  • SPAN-1 (sialylated carbonated antigen SPAN-1) 

Recommendations and guidelines by professional societies and organizations and evidence in the published peer reviewed scientific literature support the use of defined tumor markers for the diagnosis, treatment planning, treatment monitoring and/or follow up of specific cancers. However, based on the peer reviewed medical literature, improvements in meaningful health outcomes have not been proven and are still under investigation to determine their clinical utility in the management of individuals with various types of cancers. Studies comparing the tumor markers to established treatment options are lacking and management of patients based on the results of these markers have not been published and does not support these tests having sufficient sensitivity or specificity to define their clinical role.  The evidence is insufficient to determine the effects on net health outcomes including but not limited to the above indications and are therefore, considered investigational.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • 81272 KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (e.g. gastrointestinal stromal tumor (GIST), acute myeloid leukemia, melanoma), gene analysis, targeted sequence analysis (e.g. exons 8, 11, 13, 17, 18)
  • 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
  • 86316 Immunoassay for tumor antigen; other antigen, quantitative (eg. CA 50, 72-4, 549), each (this code is used for CgA)
  • 81479 Unlisted molecular pathology procedure
  • 81599 Unlisted multi-analyte assay with algorithmic analysis
  • 84999 Unlisted chemistry procedure  

 

Selected References:

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  • Jacobs IJ, et al..  Screening for ovarian cancer: a pilot randomized controlled trial.  Lancet  1999 Apr 10;353(9160):1207-10.
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  • ACOG Committee Opinion: number 280, December 2002. The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer.  Obstet Gynecol  2002 Dec;100(6):1413-6.
  • Tuxen MK, Soletormos G, Dombernowsky P. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up.  Scand J Clin Lab Invest  2002;62(3):177-88.
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  • Micke O, Bruns F, Kurowski R et al. Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys 2003; 57(1):90-7.
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  • Harris L, Fritsche H, Mennel R et al. American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer. J Clin Oncol. 2007 Nov 20;25(33):5287-312.
  • Zatelli MC, Torta M, Leon A et al. Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study. Endocr Relat Cancer. 2007 Jun;14(2):473-82.
  • Seregni E, Ferrari L, Bajetta E et al. Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Oncol. 2001;12 Suppl 2:S69-72.
  • Stirling D, Evans DGR, Pichert G et al. Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System. J Clin Oncol 2005; 23(24):5588-5596.
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  • Lim LS, Sherin K, and the American College of Preventive Medicine (ACPM) Prevention Practice Committee. Screening for Prostate Cancer in U.S. Men: ACPM Position Statement on Preventive Practice. Am J Prev Med 2008;34(2):164-70.
  • Charatcharoenwitthaya P, Enders FB, Halling KC et al. Utility of Serum Tumor Markers, Imaging, and Biliary Cytology for Detecting Cholangiocarcinoma in Primary Sclerosing Cholangitis. Hepatology 2008;48:1106-1117.
  • Juntermanns B, radunz S, Heuer M et al. Tumor markers as a diagnostic key for hilar cholangiocarcinoma. Eur J Med Res. 2010 Aug 20; 15(8):357-61.
  • Morris-Stiff G, Teli M, Jardine N et al. CA19-9 antigen levels can distinguish between benign and malignant pancreatobiliary disease. Hepatobiliary Pancreat Dis Int. 2009 Dec; 8(6):620-6.
  • Abbas G, Lindor KD. Cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Cancer. 2009; 40(1-2):19-25. Epub 2009 Aug 25.
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  • Holcomb K, Vucetic Z, Miller MC et al. Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol. 2011 Oct;205(4):358.el-6. Epub 2011 May 14.
  • American Association for the Study of Liver Disease (AASLD). ASSLD Practice Guideline. Management of Hepatocellular Carcinoma: An Update. July 2010
  • American Association for the Study of Liver Disase (AASLD). ASSLD Practice Guideline. Diagnosis and Management of Primary Sclerosing Cholangitis. February 2010.
  • The American College of Obstetrician and Gynecologists (ACOG). Committee Opinion, Number 477, March 2011. The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer. 
  • American Society of Clinical Oncology (ASCO). Guideline for Tumor Markers for Testicular Cancer and Extragonadal Germ Cell Tumors in Teenage Boys and Men.
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  • American Society of Clinical Oncology (ASCO). ASCO 2006 Update of Recommendations for the Use of Tumor Markers for Gastrointestinal Cancers, Journal of Clinical Oncology Volume 24, Number 33, November 2006.
  • National Comprehensive Cancer Network (NCCN): Version 2.2017 Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 3.2017 Uterine Neoplasms.
  • National Comprehensive Cancer Network (NCCN) Occult Primary (Cancer of  Unknown Primary) Version 2.2017. 
  • National Comprehensive Cancer Network (NCCN) Version 2.2017 Colon Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 3.2017 Rectal Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 3.2017 Neuroendocrine Tumors.
  • National Comprehensive Cancer Network (NCCN) Version 1.2013 Testicular Cancer (nonseminoma and pure seminoma). 
  • National Comprehensive Cancer Network (NCCN) Version 3.2017 Hepatobiliary Cancers.
  • National Comprehensive Cancer Network  (NCCN) Version 3.2017 Small Cell Lung Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 2.2017 Pancreatic Adenocarcinoma.
  • National Comprehensive Cancer Network (NCCN) Version 4.2013 Prostate Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 3.2017 Gastric Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 2.2017 Breast Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 2.2017 Thyroid Carcinoma.
  • National Comprehensive Cancer Network (NCCN) Version 1.2013 Endometrial Carcinoma.
  • National Comprehensive Cancer Network (NCCN) Version 2.2013 Thyroid Carcinoma.
  • National Comprehensive Cancer Network (NCCN) Soft Tissue Sarcoma Version 2.2017.
  • National Comprehensive Cancer Network (NCCN) Acute Myeloid Leukemia Version 3.2017.
  • National Comprehensive Cancer Network (NCCN) Vulvar Cancer Version 1.2016.
  • National Comprehensive Cancer Network (NCCN) Version 8.2017 Non-Small Cell Lung Cancer.
  • National Comprehensive Cancer Network (NCCN) Version 2.2017 Malignant Plural Mesothelioma.
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  • Veracyte. Afirma Thyroid FNA Analysis.   
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  • Wagner L. Patrick, Austin Frances, et. al. Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin, Ann Surg Oncol, 2013 February; 20(2): doi.1245/s10434-012-2627-5
  • Koh, Ju-Li, et al. Carbohydrate Antigen 19-9 (CA 19-9) is an Independent Prognostic  Indicator in Pseudomyxoma Peritonei Post Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy, Journal of Gastrointestinal Oncology 4.2 (2013): 173
  • Salini Ritu, Backes Floor, et. al. Posttreatment Surveillance and Diagnosis of Recurrence in Women with Gynecologic Malignancies: Society of Gynecologic Oncologists Recommendations, American Journal of Obstetrics & Gynecology June 2011.
  • Khatcheressian James, Hurley Patricia, et. al. Breast Cancer Follow-Up and Management after Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update, Journal of Clinical Oncology 2012. J Clin Oncol 31:961-965 
  • Van Poznak Catherine, Somerfield Mark R., et. al. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women with Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline, Journal of Clinical Oncology 2015.  J Clin Oncol 33:2695-2704
  • Fallahi Poupak, Giannini Riccardo, et. al. Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules. Current Genomics 2014, 15, 171-177
  • Ferris Robert, Baloch Zubair, Bernet Victor, et. al. American Thyroid Assocation Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making. Thyroid Volume 25, Number 7, 2015
  • Nikiforov Yuri, Yip Linwah, Nikiforova Marina, New Strategies in Diagnosing Cancer in Thyroid Nodules: Impact of Molecular Markers. American Assocation for Cancer Research October 13, 2015.
  • Labourier Emmanuel, Shifrin Alexander, Busseniers Anne, et. al. Molecular Testing for miRNA and DNA on Fine Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules with Indeterminate Cytology. J Clin Endocrinol Metab May 2015.
  • Interpace Diagnostics – Value Dossier ThyGenX and ThyraMIR. Prepared by Interpace Diagnostics, LLC September 16, 2015
  • ECRI. Health Technology Assessment. Afirma Thyroid Gene Expression Classifier (Veracyte, Inc) for Evaluating Thyroid Nodules of Indeterminate Cytopathologic Diagnosis. Updated November 10, 2015/Published June 6, 2014.
  • Bernet Victor, Hupart Kenneth, et. al. AACE/ACE Disease State Commentary: Molecular Diagnostic Testing of Thyroid Nodules with Indeterminate Cytopathology. Endocrine Practice April 2014 Vol. 20. No. 4, pp. 360-363
  • CMS. National Coverage Determination (NCD) for Tumor Antigen by Immunoassay CA-125 (190.28)
  • CMS. National Coverage Determination (NCD) for Tumor Antigen by Immunoassay CA 15-3/CA 27.29 (190.29)
  • CMS. National Coverage Determination (NCD) for Tumor Antigen by Immunoassay CA 19-9 (190.30)
  • UpToDate. Cancer of the Appendix and Pseudomyxoma Peritonei. Richard Swanson M.D., Jeffrey A Meyerhardt M.D., PhD. Topic last updated December 19, 2016.
  • UpToDate. Thyroid Biopsy. Douglas S Reed, M.D., Topic last updated January 20, 2016.
  • UpToDate. Screening for Ovarian Cancer. Karen J. Carlson M.D., Topic last updated August 18, 2017.
  • UpToDate. Clinical Presentation, Diagnosis, and Staging of Colorectal Cancer. Finlay A Macrae M.D., Johanna Bendell M.D., Topic last updated August 15, 2017.
  • UpToDate. Overview of the Classification and Management of Cancers of Unknown Primary Site. John D. Hainsworth M.D., F. Anthony Greco, M.D., Topic last updated June 5, 2017.
  • UpToDate. Overview of the Management of Rectal Adenocarcinoma. David P. Ryan, M.D., Miguel A. Rodriguez-Bigas M.D., Topic last updated August 21, 2017.
  • UpToDate. Clinical Manifestations and Diagnosis of Cholangiocarcinoma. Robert C Lowe, M.D., Nezam H. Afdel M.D., FRCPI, Christopher D. Anderson M.D., FACS, Kris V. Kowdley M.D., FACP, FACG, GASGE, AGAF. Topic last updated November 30, 2016.
  • Di Fabio F, Aston W, Mohamed F, Chandrakumaran K. et. al. Elevated tumor markers are normalized in most patients with pseudomyxoma peritonei 7 days after complete tumor removal. Colorectal Dis 2015 Aug;17(8):698-703
  • National Cancer Institute. Tumor Markers. Last reviewed November 4, 2015.
  • UpToDate. Management of Patients at High Risk for Breast and Ovarian Cancer. Claudine Isaacs M.D., Beth N. Peshkin MS, CGC. Topic last updated October 11, 2016.

 

Policy History:

  • August 2017 - Annual Review, Policy Revised
  • January 2017 - Interim Review, Policy Revised
  • October 2016 - Interim Review, Policy Revised
  • August 2016 - Annual Review, Policy Revised
  • December 2015 - Interim Review, Policy Revised
  • September 2015 - Annual Review, Policy Revised
  • July 2015 - Interim Review, Policy Revised
  • October 2014 - Annual Review, Policy Revised
  • March 2014 - Interim Review, Policy Revised
  • November 2013 - Interim Review, Policy Revised
  • October 2013 - Annual Review, Policy Revised
  • December 2012 - Annual Review, Policy Renewed
  • December 2011 - Annual Review, Policy Renewed
  • December 2010 - Annual Review, Policy Revised

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.