Notification



Notification Issue Date:



Medical Policy Bulletin


Title:PathFinderTG® (Independence Administrators)

Policy #:06.02.36b

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin 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 Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.


This policy only applies to members for whom Independence Administrators serves as the claims administrator. For all other Independence members, refer to the policy entitled eviCore Lab Management Program.

The intent of this policy is to communicate the coverage positions for PathFinderTG®.

For information on policies related to this topic, refer to the Cross References section in this policy.

EXPERIMENTAL/INVESTIGATIONAL

Molecular testing using PathFinderTG® is considered experimental/investigational and, therefore, not covered because the safety and effectiveness of this service cannot be established by review of the available published peer-reviewed literature.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, PathFinderTG® is not eligible for payment under the medical benefits of the Company’s commercial products because the service is considered experimental/investigational and, therefore, not covered.

Services that are experimental/investigational are a benefit contract exclusion for all products of the Company. Therefore, they are not eligible for reimbursement consideration.

Description

PathFinderTG® (RedPath Integrated Pathology Inc., Pittsburgh, PA) is a patented technology for advanced molecular topographic genotyping that obtains a genetic fingerprint of mostly acquired mutations. It is used as an adjunctive tool when microscopic analysis and special staining cannot provide a definitive diagnosis and prognostic information on specimens. PathFinderTG® can provide additional molecular analysis such as loss-of-heterozygosity (LOH)--based topographic genotyping that could be diagnostically useful since LOH is a frequent genetic alteration in many neoplasms. Combining pathologic study with molecular analysis of microdissected tissue is claimed to enhance the ability to provide more specific diagnostic information.

PathFinderTG® molecular testing involves the following steps:
  • Manual microdissection to identify and procure abnormal cells from existing pathology specimens
  • Deoxyribonucleic acid (DNA) extraction and amplification
  • DNA sequencing to identify oncogenic mutations
  • Integration of molecular information with the cytologic or histologic findings provided by the pathologists of record to provide a definitive diagnosis

Currently, PathFinderTG® molecular testing is not subject to review by the US Food and Drug Administration (FDA) because laboratory-developed tests are generally not regulated by the FDA. RedPath is accredited by the Clinical Laboratory Improvement Amendments (CLIA) and the College of American Pathologists (CAP).

In the context of available clinical history and pathology information, it has been proposed that the results of this quantitative genetic mutational analysis will provide information that will influence the management of certain cancers. However, presently, the impact of this technology on health outcomes is not known, and outcomes with this technology compared to alternatives are also not known.

The proposed published applications of PathFinderTG® pertain to multiple organ systems, including lung cancer, pancreatic and biliary tree tumors, hepatocellular carcinoma, gliomas, thyroid tumors, lacrimal gland tumors, breast tumors, genitourinary tumors, and mucinous tumors of the appendix. Much of the published peer-reviewed literature for PathFinderTG® pertains to pancreatic cysts and gliomas. In a prospective study, aspirated cyst fluid from 113 patients with pancreatic cysts were studied using PathFinderTG® (Khalid et al, 2009). Results were compared to the cytology and pathology of surgically obtained cysts. The PathFinderTG® analysis was most predictive of malignant cysts, with 96 percent specificity in identifying malignant lesions; however, the sensitivity score for these types of cysts was only 37%. Additionally, the authors acknowledged that due to selection bias, this study population consisted of a higher number of patients with malignant cysts than would be expected or reported. Conversely, the cytologic examination missed 10 out of 40 malignant lesions, all of which were correctly identified by PathFinderTG® testing. Nonetheless, these results have not been reproduced consistently to develop consensus regarding the performance characteristics for this methodology, and any incremental value – including that in treatment decision-making – that this test may provide for the relevant patient populations has yet to be established. The limitations of the study included limited follow-up, selection bias, and lack of investigator blinding to results of DNA analyses. In addition, the findings of this study and a number of other studies support the feasibility of topographic genotyping, without establishing the exact role the results will play in altering the clinical regimen in order to achieve medical benefits.

In the evaluation of suspected or known gliomas, PathFinderTG® reportedly addresses limitations of pathologic examination for diagnosing and grading through the analysis of the chromosomal 1p/19q deletion and identified LOH mutations. Tissue from 197 gliomas that were prospectively analyzed by PathFinderTG® (Finkelstein S et al, 2004) confirmed the established role of 1p/19q loss as a predictor of treatment responsiveness; however, the study demonstrated that 1p loss is more accurately ascertained by determining its temporal sequence and genomic extent of mutation acquisition. It is not clear whether the molecular data results were blinded for the classification of treatment response. The retrospective design, the lack of follow-up information for 47 of the patients, and no report of censoring due to mortality are significant study limitations. Similar limitations, including retrospective design, small sample size, and wide confidence intervals, were also seen in the major studies cited for the clinical validation of PathFinderTG® when used for the diagnosis and prognosis of gliomas.

Molecular testing is suggested to provide the opportunity to individualize the clinical and surgical management of individuals with certain cancers. However, a systematic review of available published peer-reviewed literature for molecular topographic genotyping found mainly small retrospective studies using LOH analysis with PathFinderTG® (Trikalinos et al, 2010). Although these studies describe the molecular profiles of different tumors obtained by PathFinderTG®, they do not assess the ability of PathFinderTG® to improve clinical outcomes relevant to individuals.

Evidence reviewed for the representative uses of PathFinderTG® has significant limitations. Demonstrating the utility of a test for diagnostic and prognostic purposes or to predict therapeutic response requires that results accurately inform clinical decision-making in a manner leading to a net health benefit defined by clinical outcomes. Results also must be clearly reproducible, as shown by applying the test (with predefined cutoff points) to independent samples for validation. The impact of this technology on health outcomes is unknown and outcomes with this technology compared with existing alternatives (ie, incremental value) are unknown. Additional robust data are needed for PathFinderTG® testing for all indications, including evaluation of pancreatic cyst fluid, suspected/known gliomas, and Barrett esophagus.
References


Alberts B, Johnson A, Lewis J, et al. Molecular biology of the cell. 5th ed. New York, NY: Garland Science; 2008.

Aldape K, Burger PC, Perry A. Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. Arch Pathol Lab Med. 2007;131(2):242-251.

Cai G, Siddiqui U, Aslanian H, et al. Molecular analysis of pancreatic cystic fluid: correlation with cytologic diagnosis and surgical follow-up. CT USCAP; March 23, 2010.

Coons SW, Johnson PC, Scheithauer BW, et al. Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer. 1997;79(7):1381-1393.

Fasanella KE, McGrath KM, Sanders M, et al. Pancreatic endocrine tumor EUS-guided FNA DNA microsatellite loss and mortality. Gastrointest Endosc.2009;69(6):1074-1080.

Finkelstein SD, Marsh W, Demetris AJ, et al. Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma. Hepatology. 2003;37(4):871-879.

Finkelstein SD, Mohan D, Hamilton RL, et al. Microdissection-based genotyping assists discrimination of reactive gliosis from glioma. Am J Clin Pathol.2004;121(5):671-678.

Furukawa T, Sunamura M, Horii A. Molecular mechanisms of pancreatic carcinogenesis. Cancer Sci. 2006;97(1):1-7.

Hayes, Inc. Hayes Genetic Test Evaluation (Report). PathFinderTG® Test for Pancreatic Cancer. Lansdale, PA: Hayes, Inc.; November 30, 2011.

Hayes, Inc. Hayes Genetic Test Evaluation (Report). PathFinderTG® Test (RedPath Integrated Pathology Inc.) for the Diagnosis of Breast Cancer. Lansdale, PA: Hayes, Inc.; July 10, 2011.

Hunt JL, Finkelstein SD. Microdissection techniques for molecular testing in surgical pathology. Arch Pathol Lab Med.2004;128(12):1372-1378.

Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol.2007;102(10):2339-2349.

Khalid A, McGrath KM, Zahid M, et al. The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology. Clin Gastroenterol Hepatol.2005;3(10):967-973.

Khalid A, Nodit L, Zahid M, et al. Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses. Am J Gastroenterol.2006;101(11):2493-2500.

Khalid A, Pal R, Sasatomi E, et al. Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples. Gut.2004;53(12):1860-1865.

Khalid A, Zahid M, Finkelstein SD, Maitra A. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc. 2009;69(6):1095-1102.

Koorstra JB, Hustinx SR, Offerhaus GJ, et al. Pancreatic carcinogenesis. Pancreatology.2008;8(2):110-125.

Lapkus O, Gologan O, Liu Y, et al. Determination of sequential mutation accumulation in pancreas and bile duct brushing cytology. Mod Pathol. 2006;19(7):907-913.

Lassman AB, Holland EC. Incorporating molecular tools into clinical trials and treatment for gliomas? Curr Opin Neurol. 2007;20(6):708-711.

Mohan D, Finkelstein SD, Swalsky PA, et al. Microdissection genotyping of gliomas: therapeutic and prognostic considerations. Mod Pathol.2004;17(11):1346-1358.

Muller P, Ostwald C, Puschel K, et al. Low frequency of p53 and ras mutations in bile of patients with hepato-biliary disease: a prospective study in more than 100 patients. Eur J Clin Invest.2001;31(3):240-247.

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.

Pitman MB, Lewandrowski K, Shen J, et al. Pancreatic cysts: preoperative diagnosis and clinical management. Cancer Cytopathol.2010;118(1):1-13.

Popovic Hadzija M, Korolija M, Jakic Razumovic J, et al. K-ras and Dpc4 mutations in chronic pancreatitis: case series. Croat Med J.2007;48(2):218-224.

Sawhney MS, Devarajan S, O'Farrel P, et al. Comparison of carcinoembryonic antigen and molecular analysis in pancreatic cyst fluid. Gastrointest Endosc.2009;69(6):1106-1110.

Singh M, Maitra A. Precursor lesions of pancreatic cancer: molecular pathology and clinical implications. Pancreatology.2007;7(1):9-19.

Shen J, Brugge WR, Dimaio CJ, et al. Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis. Cancer Cytopathol.2009;117(3):2172-27.

Shirasaki F, Takata M, Hatta N, et al. Loss of expression of the metastasis suppressor gene KiSS1 during melanoma progression and its association with LOH of chromosome 6q16.3-q23. Cancer. 2001;61(20):7422-7425.

Sreenarasimhaiah J, Lara LF, Jazrawi SF, 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):163-168.

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(1-2):17-32.

Thiessen B, Maguire JA, McNeil K, et al. Loss of heterozygosity for loci on chromosome arms 1p and 10q in oligodendroglial tumors: relationship to outcome and chemosensitivity. J Neuro-Oncol.2003;64(3):271-278.

Trikalinos TA, Terasawa T, Raman G, et al. A systematic review of loss-of-heterozygosity based topographic genotyping with PathfinderTG®: technology assessment report. Rockville, MD: Agency for Healthcare Research and Quality, US Dept of Health and Human Services; 2010.

Uehara H, Nakaizumi A, Tatsuta M, et al. Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations. Am J Gastroenterol.1999;94(9):2513-2518.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

THE FOLLOWING CODES ARE USED TO REPRESENT PATHFINDERTG®:


84999, 89240



Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

This service is experimental/investigational for all diagnoses.


HCPCS Level II Code Number(s)

N/A


Revenue Code Number(s)

N/A

Coding and Billing Requirements



Policy History

Revisions for 06.02.36b
12/19/2018This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 07/01/2016
Version Issued Date: 07/01/2016
Version Reissued Date: 12/19/2018

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