Adequacy of Samples Obtained by Endobronchial Ultrasound with Transbronchial Needle Aspiration for Molecular Analysis in Patients with Non-Small Cell Lung Cancer Systematic Review and Meta-Analysis

Rationale: Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) are commonly used for the diagnosis and mediastinal staging of lung cancer. Molecular markers are becoming increasingly important in patients with lung cancer to define targetable mutations suitable for personalized therapy, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species proto-oncogene (ROS1), and programmed death-ligand 1 (PD-L1). Objectives: To evaluate the adequacy of EBUS-TBNA-derived tissue for molecular analysis. Methods: We searched the MEDLINE, LILACS, www.clinicaltrials.gov, and Epistemonikos databases through January 2018. Data Extraction: Two independent reviewers performed the data search, quality assessment, and data extraction. We included both prospective and retrospective studies; risk of bias was evaluated using the ROBINS-I tool. The primary outcome was the proportion of adequate samples obtained by EBUS-TBNA for molecular analysis. Data were pooled by using a binary random effects model. Finally, evidence was rated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results: A total of 33 studies including 2,698 participants were analyzed. In 28 studies that evaluated EBUS-TBNA for the identification of EGFR mutations, the pooled probability of obtaining a sufficient sample was 94.5% (95% confidence interval CI], 93.2-96.4%). For identification of ALK mutations, the pooled probability was 94.9% (95% CI, 89.4-98.8%). Finally, the prevalence of EGFR mutation was 15.8% (95% CI, 12.1-19.4%), and the prevalence of ALK mutation was 2.77% (95% CI, 1.0-4.8%). Data for ROS1 and PD-L1 mutations were not suitable for meta-analysis. Conclusions: EBUS-TBNA has a high yield for molecular analysis of both EGFR and ALK mutations. However, the suitability of TBNA samples for next-generation sequencing is uncertain and should be explored in further studies.