Medical Policy: 02.04.52
Original Effective Date: July 2015
Reviewed: June 2020
Revised: June 2020
This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.
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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.
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 ‘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). This patented diagnostic testing system is marketed under the specific test names of PancraGEN® and BarreGEN, is also being studied for pancreatobiliary cancer. It is available only through Interpace Diagnostics.
The testing involves the following steps:
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.
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.
Currently, if a transabdominal ultrasound confirms the presence of a lesion, an abdominal computed tomography scan is performed to confirm the presence of the mass and determine disease extent. If the computed tomography provides enough information to recommend a resection and if the patient is able to undergo the procedure, no further testing is necessary. If the diagnosis remains unclear, additional procedures may be recommended. Symptomatic patients undergo cytology testing. If results from cytology testing are inconclusive, fluorescent in situ hybridization molecular testing of solid pancreaticobiliary lesions is recommended.
Surveillance for esophageal adenocarcinoma is recommended for those diagnosed with Barrett esophagus. However, there are few data to guide recommendations about management and surveillance, and many issues are controversial. In 2015 guidelines from the American College of Gastroenterology (ACG) and a consensus statement from an international group of experts (Benign Barrett's and Cancer Taskforce) on the management of Barrett esophagus were published., ACG recommendations for surveillance are stratified by the presence of dysplasia. When no dysplasia is detected, ACG has reported the estimated risk of progression to cancer for patients ranges from 0.2% to 0.5% per year and ACG has recommended endoscopic surveillance every 3 to 5 years. For low-grade dysplasia, the estimated risk of progression is about 0.7% per year, and ACG has recommended endoscopic therapy or surveillance every 12 months. For high-grade dysplasia, the estimated risk of progression is about 7% per year, and ACG has recommended endoscopic therapy. The Benign Barrett's and Cancer Taskforce consensus group did not endorse routine surveillance for people with no dysplasia and was unable to agree on surveillance intervals for low-grade dysplasia.
Given the rare occurrence but the poor prognosis of pancreatic cancer, there is a need to balance potential early detection of malignancies while avoiding unnecessary surgical resection of cysts. Several guidelines address the management of pancreatic cysts, but high-quality evidence to support these guidelines is not generally available. Although recommendations vary, first-line evaluation usually includes an examination of cyst cytopathologic or radiographic findings and cyst fluid carcinoembryonic antigen. An international consensus panel published statements on the management of IPMN and mucinous cystic neoplasm of the pancreas. These statements are referred to as the Fukouka Consensus Guidelines. The panel recommended surgical resection for all surgically fit patients with main duct IPMN or mucinous cystic neoplasm. For branch duct IPMN, surgically fit patients with cytology suspicious or positive for malignancy are recommended for surgical resection, but patients without "high-risk stigmata" or "worrisome features" may be observed with surveillance. "High-risk stigmata" are obstructive jaundice in proximal lesions (head of the pancreas); the presence of an enhancing solid component within the cyst; or 10 mm or greater dilation of the main pancreatic duct. "Worrisome features" are pancreatitis; lymphadenopathy; cyst size 3 cm or greater; thickened or enhancing cyst walls on imaging; 5 to 10 mm dilation of the main pancreatic duct; or abrupt change in pancreatic duct caliber with distal atrophy of the pancreas.
The NCCN Guidelines on Pancreatic Adenocarcinoma (Version 1.2020), Hepatobiliary Cancers (Version 3.2020), Esophageal and Esophagogastric Junction Cancers (Version 2.2020), Central Nervous System Cancers (Version 1.2020) do not mention Molecular topographic genotyping.
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.
The College (2018) published guidelines on the diagnosis and management of pancreatic cysts. The guidelines stated that the evidence for the use of molecular biomarkers for identifying high-grade dysplasia or pancreatic cancer is insufficient to recommend their routine use. However, molecular markers may help identify intraductal papillary mucinous neoplasms and mucinous cystic neoplasms in cases with an unclear diagnosis and if results are likely to change the management (conditional recommendation; very low quality evidence).
Current evidence-based guidelines from other medical professional organizations do not include topographic genotyping with strong evidence for recommendation.
Refer to policy 02.01.23 Treatment of GERD and Barrett’s esophagus for additional information on treatment of Barrett’s esophagus
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:
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.
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