Medical Policy: 02.04.52 

Original Effective Date: July 2015 

Reviewed: June 2017 

Revised: June 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:

Molecular topographic genotyping, also called molecular anatomic pathology, combines advanced molecular genetics with current pathology practices for a definitive diagnosis from existing specimens.  The results are advertised to provide useful information for physicians to plan the best course of treatment for each patient's unique diagnosis.

 

The RedPath Integrated Pathology ‘PathFinderTG®’ test is not a single test, but is an advanced pathology service that includes microdissection, selection of regions to be analyzed, analysis of these regions using a variety of molecular tests (i.e., topographic genotyping).

 

The testing involves the following steps:

  • Manual microdissection to identify and procure abnormal cells from existing pathology specimens
  • DNA extraction and amplification (e.g., polymerase chain reaction [PCR])
  • DNA sequencing to identify oncogenic mutations
  • Integration of this molecular information with the cytologic or histologic findings provided by the pathologist of record to provide a definitive diagnosis

For some specimens such as fluid aspirates, DNA is extracted from the fluid, since there may be little or no cellular content. The molecular testing consists of applying panels of molecular markers previously defined for each organ system or clinical question.

  

Some of the tests RedPath offer (e.g., 1p/19q loss, microsatellite instability) are offered by other laboratories as single clinical tests and RedPath has sold the tests to other companies as well. The remainder of the tests RedPath offers (e.g., KRAS point mutation and loss of heterozygosity [LOH] panels) are typically performed in research settings. The aim of PathFinderTG® testing is to integrate molecular findings into the pathology diagnosis.

 

There is insufficient evidence in the published, peer-reviewed, scientific literature to demonstrate that topographic genotyping pathology can be used as methods to assist in the diagnosis or management of individuals with cancer when microscopic analysis and staining fail to provide a definitive diagnosis. This testing has not been adequately compared with established testing methods and impact on health outcomes is not known at this time. The clinical utility of topographic genotyping and the PathfinderTG® in the diagnosis and management of cancer has not yet been established through well-designed clinical trials. Peer reviewed studies that describe the analytical validity or investigate the clinical utility of the topographic genotyping tests are lacking.  The manufacturer has indicated that the technology is meant as an adjunct to first-line testing but no algorithm for combining with consensus guidelines for decision making has been proposed.

 

This molecular test is marketed as a way to provide definitive diagnoses and prognostic information and predict responses to chemotherapy. While integrating the molecular information that a test like PathFinderTG® provides is of interest and the subject of research for neoplasms, currently the specific molecular features, associated genetic biomarkers and their relationships with clinical outcomes, are not well-defined. Accordingly, their role in clinical decision making, including selecting treatment options, has not been defined.

 

Practice Guidelines and Recommendations


The NCCN Guidelines on Pancreatic Adenocarcinoma (Version 2.2017), Hepatobiliary Cancers (Version 2.2017), Esophageal and Esophagogastric Junction Cancers (Version 1.2017), Central Nervous System Cancers (Version 1.2016) Breast Cancer (Version 2.2017) do not mention Molecular topographic genotyping (PathFinder TG).

 

The American Gastroenterological Association guidelines have no recommendations for the use of topographic genotyping for evaluating pancreatic cysts.

 

The American Society of Gastrointestinal Endoscopy guideline (2016) states Molecular analysis (which requires only 200 mL of fluid) may be most useful in small cysts with nondiagnostic cytology, equivocal cyst fluid CEA results, or when insufficient fluid is present for CEA testing. However, additional research is needed to determine the precise role molecular analysis of cyst fluid will play in evaluating pancreatic cystic lesions.

 

Current evidence-based guidelines from other medical professional organizations do not include topographic genotyping with strong evidence for recommendation.

 

Prior Approval:

 

Not applicable

 

Policy:

  • Molecular topographic genotyping including PathFinderTG® system, PancraGen™ and BarreGen™or any other test utilizing molecular topographic genotyping is considered investigational for all indications including, but not limited to:

    • evaluation of pancreatic cyst fluid (now called PancraGen™)

    • evaluation of suspected or known gliomas  (PathFinderTG® Glioma)

    • evaluation of Barrett’s esophagus (now called BarreGen™)

    • evaluation of biliary strictures (PathFinderTG® Biliary)

    • evaluation to differentiate tumors

There is insufficient evidence to support a conclusion concerning the health outcomes or benefits associated with this procedure. The testing accuracy is questioned by currently available studies. The clinical utility of topographic genotyping in the diagnosis and management of cancer has not yet been established through well-designed clinical trials.

 

This test has multiple potential uses including use in diagnosis, determining prognosis, and predicting response to therapies. All uses, in all conditions, are considered investigational.

 

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
  • 89240  Unlisted miscellaneous pathology test
  • 81599  Unlisted multianalyte assay with algorithmic analysis
  • 81479  Unlisted molecular pathology procedure

 

Selected References:

  • Nikiforova MN, et al. Molecular diagnostics of gliomas. Arch Pathol Lab Med 2011 Jul;135(7):558-68.
  • Sawhney MS, et al. Comparison of carcinoembryonic antigen and molecular analysis in pancreatic cyst fluid. Gastrointest Endosc 2009;69:1106-10.
  • Shen J, et al. Molecular analysis of pancreatic cyst fluid. Cancer Cytopathol 2009;117:217-227.
  • Sreenarasimhaiah J, et al. A comparative analysis of pancreas cyst fluid CEA and histology with DNA mutational analysis in the detection of mucin producing or malignant cysts. JOP 2009;10(2):163-8.
  • Trikalinos TA, et al. A systematic review of loss-of-heterozygosity based topographic genotyping with PathfinderTG®. AHRQ Technology Assessment Program (Project ID GEND0308). 2010 Mar 1 [http://www.cms.gov/determinationprocess/downloads/id68ta.pdf]
  • Tse DT, et al. Microdissection genotyping analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma. Am J Ophthalmol 2006 Jan;141(1):54-61.
  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Breast, version 1.2017.
  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma, version 2.2017.
  • RedPath Integrated Pathology Overview & copy;2013.
  • Centers for Medicare and Medicaid Services, CMS Manual System and other CMS publications and services
  • National Comprehensive Cancer Network NCCN clinical practice guidelines in oncology: esophageal and esophagogastric junction cancers, version 1.2017
  • National Comprehensive Cancer Network NCCN clinical practice guidelines in oncology: hepatobiliary cancers, version 2.2017
  • Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6(2-Jan):17-32.
  • Oh HC, Kim MH, Hwang CY, et al. Cystic lesions of the pancreas: challenging issues in clinical practice. Am J Gastroenterol. 2008;103(1):229-239.
  • Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol. 2007;102(10):2339-2349.
  • National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: central nervous system cancers, version 1.2016.
  • Loren D, Kowalski T, Siddiqui A, et al. Influence of integrated molecular pathology test results on real-world management decisions for patients with pancreatic cysts: analysis of data from a national registry cohort. Diagnostic Pathology. 2016;11:5.
  • Muthusamy, V. Chandrasekhara, V. Acosta, R. et. al The role of endoscopy in the diagnosis and treatment of cystic pancreatic neoplasms, ASGE Standards of practice committee,  Gastrointest Endosc 2016;84:1-9 

 

Policy History:

  • June 2017 - Annual Review, Policy Revised
  • June 2016 - Annual Review, Policy Revised
  • July 2015 - New Medical Policy, Policy Implemented

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.