LCD L37857: MolDX: Envisia™, Veracyte™, Idiopathic Pulmonary Fibrosis Diagnostic Test

This is a laboratory test which will assist physicians caring for patients who have developed pulmonary (lung) scarring.

This policy provides limited coverage for the Envisia™ Genomic Classifier (Veracyte™, Inc., South San Francisco, CA), a tissue based multi-analyte assay with algorithm analysis test (hereafter called Envisia™) for interstitial lung disease (ILD) patients who are suspected of having idiopathic pulmonary fibrosis (IPF) and who do not have a definitive usual interstitial pneumonia (UIP) pattern by high resolution computed tomography (HRCT) or other known cause of ILD. IPF suspicion increases significantly in patients greater than 60 years of age when HRCT is not definitive, and comorbidities in this population make clinicians reluctant to perform surgical lung biopsy to obtain a diagnosis due to significant procedure morbidity and mortality. Envisia™ testing is performed on less-invasive bronchoscopy transbronchial biopsy (TBB) samples and is intended to provide a categorical UIP or non-UIP result that along with clinical and radiographic information may guide treatment without the need or risk of surgical lung biopsy.

ILD is a heterogenous group of lung disorders, for which an accurate diagnosis is critical to determining appropriate intervention for a given patient. 1 IPF is one of the most common interstitial lung diseases and frequently implicated when there is no other known cause of ILD, and often necessitates surgical lung biopsy to obtain a diagnosis. The natural history of IPF is described as progressive decline in pulmonary function until eventual death from respiratory failure or complicating comorbidity. Patients with IPF under age 50 are rare, with disease typically presenting in the sixth and seventh decades of life and incidence increasing with older age. 2 The incidence of IPF is estimated to be between 8-17 per 100,000 person years in the general population, 3 and mean survival after diagnosis is 2 to 5 years. 2 A study evaluating Medicare claims data from 2000 to 2011 found that the incidence of IPF in the Medicare population is significantly higher, 93.7 per 100,000 person years, than observed in the general population. 4

Historically, lung transplantation has been the only proven treatment for IPF, but its use has been limited due to supply of donor organs and poor survival for IPF patients relative to other candidates. 5 Recent clinical trials evaluating the efficacy of anti-fibrotic therapy in patients diagnosed with IPF have demonstrated a 50% reduction in the proportion of patients that have absolute pulmonary function decline of 10% or greater, an increase in the rate of patients with no pulmonary function decline, and improved progression free survival. 6,7 These findings suggest an improvement in patient outcomes when IPF is accurately diagnosed and treated.

The pattern of UIP is the hallmark of an IPF diagnosis. The development of evidence based diagnostic criteria for IPF in 2011 by an international consortium of pulmonary societies, including the American Thoracic Society (ATS), requires exclusion of known causes of ILD, a definitive UIP pattern by HRCT, or specific combinations of UIP by HRCT and surgical pathology. 2 Despite efforts to standardize these criteria, interobserver agreement of categorical UIP diagnosis by HRCT following the ATS guideline is moderate (52%) among expert thoracic radiologists. 8 And recent studies suggest that a minority (13%) of patients being evaluated for IPF obtain a definitive UIP diagnosis by HRCT, necessitating surgical biopsy as the next diagnostic step. 9

Diagnosis of IPF by HRCT alone is challenging. As shown in Table 1, a diagnosis of UIP by HRCT requires the coexistence of multiple radiographic features of a UIP pattern and absence of features inconsistent with UIP. Those features consistent with IPF may also be found in patients with other common ILDs of known cause, such as chronic hypersensitivity pneumonitis (HP). 10 Although guidelines place significant importance upon a thorough clinical history to identify ILDs of known cause, up to 30% of patients with HP are ultimately diagnosed without identifying a known cause, further complicating clinician’s ability to distinguish these diseases. 11 Additional non-surgical biopsy approaches to diagnosing ILDs of known cause that may be utilized include bronchoalveolar lavage (BAL) for the identification of lymphocytosis which may suggest occult hypersensitivity pneumonitis, and TBB which is useful in diagnosing granulomatous disorders, such as sarcoidosis. 2 While highly specific for these indications and significantly less risk than a surgical biopsy, pathologic review of BAL and TBB specimens have not shown to be sensitive for detecting a UIP pattern. 12