Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Adenocarcinoma (NSCLC)

Treatment: Genetic Testing 

The insurer denied the Genetic Testing 81201, 81272, 81173, 81321, 81210, 81275, 81310, 81120, 81235, 81276, 81311, 81121, 81270, 81293, 81314, 81400, 81401, 81402, 81403, 81404, 81405, 81406 and 81407. The denial was upheld.   

Reviewer # 1:

This is a female patient with a diagnosis of adenocarcinoma (NSCLC). The patient presented to her primary care physician with complaints of coughing, weight loss, and shortness of breath. A computed tomography from the prior year showed a 2.7cm nodule in the right lower pulmonary lobe, slightly increased from 2.6 cm on prior study, stable small left pulmonary nodules. Guardant360 test was performed. 

The scientific evidence in peer-reviewed literature does not support a result of improvement in health outcome. Guardiant is one of several panels of tumor markers designed to give the oncologist an option of treating in a personalized manner directed to the specific markers that the cancer expresses. It is a clinical diagnostic test based on sequencing 74 genes and Guardiant claims to be highly accurate in identifying genomic alterations. The NCCN (2020) do not recommend liquid biopsy version of Guardiant360. 

Per Lanman, et al. (2015), "This study validates the Guardant360 assay across many cancer types, but only in stage III/IV cancers. Analysis of early stage tumors and indolent tumors may have higher false negative rates. Additionally, primary brain tumors may not release DNA into the systemic circulation due to the blood-brain barrier and thus this assay should be specifically validated for this indication in future studies [28]. A further limitation of this study is that individual substudies had small sample sizes, however there were consistent results between the findings of near-perfect analytic specificity (comparison to whole exome) and clinical specificity (comparison to tissue NGS) results, and the clinical sensitivity reported here for cfDNA of 85.0% across 54 genes is comparable to that reported by on a single-gene cfDNA assay of 87.2% [28]."

Per McCoach, C. E., et al. (2018), "Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) can provide a non-invasive method of obtaining and evaluating tumor DNA in patients with cancer. cfDNA-based diagnostics can identify oncogenes at initial diagnosis when tissue samples are insufficient or unobtainable, which can guide effective first line therapy and can identify actionable resistance mechanisms at disease progression. Prior work has demonstrated the feasibility of using "hotspot" and comprehensive cfDNA profiling for identification of activating mutations and therapeutic resistance mechanisms in EGFR-mutated NSCLC.1824 However, its utility in evaluating ALK gene fusions has not been assessed on a large scale...."      

The NCCN does recommend "broader molecular profiling" for non-small lung cancer; however, the NCCN guidelines also indicate that the use of cell-free tumor DNA testing to have significantly compromised sensitivity with high false negative rates, can identify alterations that are unrelated to a lesion of interest, and the standards for analytical performance have not been established for this type of test.     

Guardant 360 is not likely to be more beneficial than any of the standard treatments/procedures for this patient.                                                    

The carrier's denial of Genetic Testing 81201, 81272, 81173, 81321, 81210, 81275, 81310, 81120, 81235, 81276, 81311, 81121, 81270, 81293, 81314, 81400, 81401, 81402, 81403, 81404, 81405, 81406 and 81407 (Guardant 360 blood test) should be upheld.