Medical Policy: 02.04.60 

Original Effective Date: August 2016 

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:

Plasma based proteomic screening is a molecular diagnostic test available in the diagnostic workup of pulmonary nodules. To rule out malignancy, invasive diagnostic procedures such as CT-guided biopsies, bronchoscopies or video assisted thoracoscopy are often required but each carry procedure related complications ranging from post procedure pain to pneumothorax. Molecular diagnostic tests have been proposed to aid in risk-stratifying patients to eliminate or necessitate the need for subsequent invasive diagnostic procedures.

 

Pulmonary nodules are common clinical problem that may be found as an incidental finding on a chest x-ray or CT scan or in the context of lung cancer screening studies of smokers. The primary question following detection of pulmonary nodules is the probability of malignancy, with subsequent management based on various factors such as the radiographic characteristics of the pulmonary nodule (e.g. size, shape, density) and patient factors (e.g. age, smoking history, previous cancer history, family history, environmental/occupational exposures). The challenge in the diagnostic workup for pulmonary nodules is appropriately ruling-in patients for invasive diagnostic procedures and ruling-out patients who should forego invasive diagnostic procedures.

 

Proteomics is the study of the structure and function of proteins, including antibodies. The study of the concentration, structure and other characteristics of proteins, including antibodies contained in various bodily tissues, fluids and other materials has been proposed as a method of identifying and managing various diseases, including cancers.  In proteomics, multiple test methods are used to study proteins. Immunoassays use antibodies to detect the concentration and/or structure of proteins. Mass spectrometry is an analytic technique that ionizes proteins into smaller fragments and determine mass and composition to identify and characterize proteins. 

Plasma-Based Proteomic Screening for Pulmonary Nodules

 

Plasma-based proteomic screening is a molecular test that may help physicians risk-stratify pulmonary nodules as likely benign, thereby increasing the number of patients who can confidently choose serial CT scans of their nodules (“active surveillance”), instead of invasive procedures like surgery and biopsy, that carry significant risks and costs. Additionally, plasma-based proteomic screening may also determine a likely malignancy in clinically low risk or intermediate risk pulmonary nodules thereby allowing for earlier detection in a subset of patients.

 

Xpresys Lung is plasma-based proteomic screening test that measures the relative abundance of 11 proteins across multiple disease pathways associated with lung cancer using an analytic technique called multiple reaction monitoring mass spectroscopy (MRM-mass spec). The role of this test is to aid physicians in differentiating likely benign, versus likely malignant nodules in patients. If the test yields a “likely benign” result, patients may choose active surveillance via serial CT scans to monitor the pulmonary nodule(s). If the test yields a “likely malignant” result, invasive diagnostic procedure would be indicated. The test is therefore only used in the management of pulmonary nodules to rule-in or rule-out invasive diagnostic procedures and does not provide a diagnosis of lung cancer.

 

Summary

Based on review of the peer reviewed medical literature for individuals with pulmonary nodules discovered by imaging who receive plasma-based proteomic screening, the evidence includes an analytic validity study, prospective cohort and prospective-retrospective studies. Direct evidence of clinical utility is limited.  Additional randomized controlled studies are necessary to establish the impact of this testing in decreasing unnecessary invasive procedures or surgeries and concurrently  decreasing cancer related deaths and other positive outcomes. Also, no professional society guidelines indicate the utilization of plasma-based proteomic screening (Xpresys Lung) for risk assessment and early screening for lung cancer in patients with pulmonary nodules. The evidence is insufficient to determine the effects of this testing on net health outcomes.

 

Regulatory Status

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory developed tests (LDTs) must meet general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Xpresys Lung test is available under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

 

Practice Guidelines and Position Statements

No practice guidelines and position statements were identified.

 

Prior Approval:

Not applicable

 

Policy:

See also medical policy 02.04.55 Epidermal Growth Factor Receptor (EGFR) Testing

 

Plasma-based proteomic screening testing, including but not limited to the following, for risk assessment and early screening for lung cancer in patients with pulmonary is considered investigational:

  • Xpresys Lung

Based on review of the peer reviewed medical literature for individuals with pulmonary nodules discovered by imaging who receive plasma-based proteomic screening, the evidence includes an analytic validity study, prospective cohort and prospective-retrospective studies. Direct evidence of clinical utility is limited.  Additional randomized controlled studies are necessary to establish the impact of this testing in decreasing unnecessary invasive procedures or surgeries and concurrently decreasing cancer related deaths and other positive outcomes. Also, no professional society guidelines indicate the utilization of plasma-based proteomic screening (Xpresys Lung) for risk assessment and early screening for lung cancer in patients with pulmonary nodules. The evidence is insufficient to determine the effects of this testing on net health outcomes.

 

Procedure Codes and Billing Guidelines:

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

  • 84999  Unlisted chemistry procedure (when specified as Xpresys Lung)

 

Selected References:

  • Jaklitsh M, Jacobson F, Austin J, et. al. The American Association for Thoracic Surgery Guidelines for Lung Cancer Screening using Low Dose Computed Tomography Scans for Lung Cancer Survivor. The Journal of Thoracic and Cardiovascular Surgery 2012, Volume 144, Number 1.
  • Detterbeck F, Mazzone P, Naidich D, et. al. Diagnosis and Management of Lung Cancer, 3rd ed. American College of Chest Physicians Evidence Based Clinical Practice Guidelines. Chest 2013;143(5)(Suppl):e78S-e92S
  • Bach P, Mirkin J, Oliver T, Azzoli C, et. al. The Role of CT Screening for Lung Cancer in Clinical Practice. JAMA Vol 307, No. 22 June 13, 2012
  • Leighl N, Rekhtman N, Biermann W, et. al. Molecular Testing for Selection of Patients with Lung Cancer for Epidermal Growth Factor Response and Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Guideline. Journal of Clinical Oncology Volume 32, Number 32, 3673-3679 November 10, 2014
  • National Comprehensive Cancer Network (NCCN) Lung Cancer Screening Version 2.2016.
  • National Comprehensive Cancer Network (NCCN) Non-Small Cell Lung Cancer Version 4.2016.
  • National Comprehensive Cancer Network (NCCN) Small Cell Lung Cancer Version 1.2017.
  • U.S. Preventative Services Task Force (USPSTF) Lung Cancer Screening December 2013.
  • UpToDate. Screening for Lung Cancer. Mark E Deffebach M.D., Linda Humphrey M.D., Topic last upated June 10, 2016.
  • UpToDate. Overview of the Initial Evaluation, Diagnosis, and Staging of Patients with Suspected Lung Cancer. Karl W. Thomas M.D., Michael K. Gould M.D., M.S.. Topic last updated July 14, 2016.
  • UpToDate. Overview of the Initial Evaluation, Treatment and Prognosis of Lung Cancer. David E. Midthun M.D., Topic last updated March 9, 2016.
  • Innovative Diagnostic Laboratory. EarlyCDT Lung
  • Integrated Diagnostics, Inc. Xpresys Lung.
  • Vachani A, Pass HI, Rom WN, et. al. Validation of a multiprotein plasma classifier to identify benign lung nodules. J Thorac Oncol 2015 Apr;10(4):629-34
  • Vachani A, Hammoud Z, Spingmeyer S, et. al. Clinical utility of a plasma protein classifier for  indeterminate lung nodules. Lung 2015 Dec;193(6):1023-7
  • Tanner NT, Aggarwal J, Gould MK, et. al. Management of pulmonary nodules by community pulmonologists: a multicenter observational study. Chest 2015 Dec;148(6):1405-14
  • Vachani A, Tanner NT, Aggarwal J. et. al. Factors that influence physician decision making for indeterminate pulmonary nodules. Ann Am Thorac Soc 2014 Dec;11(10):1586-91
  • Li XJ, Hayward C, Fong PY, et. al. A blood-based proteomic classifier for the molecular characterization of pulmonary nodules. Sci Transl Med. 2013 Oct 16;5(207):207ra142
  • Murray A, Chapman CJ, Healey G. et.al. Technical validation of an autoantibody test for lung cancer. Ann Oncol 2010 Aug;21(8):1687-93
  • Chapman CJ, Healey GF, Murray A, et. al. EarlyCDT Lung Test: improved clinical utility through additional autoantibodyd assays. Tumour Biol 2012 Oct;33(5):1319-26
  • Lam S, Boyle P, Healey GF, et. al. EarlyCDT-Lung: an immunobiomarker test as an aid to early detection of lung cancer. Cancer Prev Res 2011 Jul;4(7):1126-34
  • Boyle P, Chapman CJ, Holdenrieder S, et. al. Clinical validation of an autoantibody test for lung cancer. Annals of Oncology May 2010
  • Chapman CJ, Murray A, McElveen JE, et. al. Autoantibodies in lung cancer: possibilities for early detection and subsequent cure. Thorax 2008 Mar;63(3):228-33
  • UpToDate. Diagnostic Evaluation and Management of the Solitary Pulmonary Nodule. Steven E. Weinberger M.D., Shaunagh McDermott M.D., Topic last updated June 22, 2017.
  • Pecot CV, Li M, Zhang XJ, et. al. Added value of serum proteomic classifier for the molecular characterization of pulmonary nodules. Sci Transl Med Oct 16 2013;5(207):207ra142. PMID 24132637
  • Gould M, Donington J, Lynch W, et. al. Evaluation of Individuals with Pulmonary Nodules: When is it Lung Cancer? Diagnosis and Management of Lung Cancer, 3rd ed. American College of Chest Physicians Evidence Based Clinical Practice Guidelines. Chest 2013:143(5)(Suppl)e93S-e120S

 

Policy History:

  • August 2017 - Annual Review, Policy Revised
  • August 2016 - New Policy

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.

 

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