Feasibility of comprehensive genotyping specimens from radial endobronchial ultrasonography and electromagnetic navigation bronchoscopy

INTRODUCTION: Mini-invasive bronchoscopic techniques (such as radial endobronchial ultrasonography (rEBUS) and electromagnetic navigation (EMN)) have been developed to reach the peripheral lung but result in small samples. The feasibility of an adequate molecular testing from these specimens has been very little studied. METHODS: We retrospectively reviewed EMN and rEBUS procedures performed in patients diagnosed with lung cancer in our institution in 2017 and 2018. We analysed the sensitivity for rEBUS and EMN and each sampling method, and the feasibility of a comprehensive molecular testing. RESULTS: In total, 317 rEBUS and 14 EMN were performed. Median sizes of tumours were 16 and 32 mm for EMN and rEBUS, respectively. Overall sensitivity for rEBUS and EMN was 84.3%. Cytology was found to be complementary with biopsies, with 13.3% of cancer diagnosed on cytology while biopsies were negative. Complication rate was 2.4% (pneumothorax 1.5%, mild haemoptysis 0.9%). Genotyping (immunohistochemistry for ROS1 and ALK followed by fluorescence in situ hybridisation if positive and hybrid capture next-generation sequencing covering 48 genes), when ordered (n=188), was feasible in 69.1% (EGFR 17.7%, KRAS 31.7%, BRAF 4.8%, ALK 1.2%, MET 3.1%, HER2 0.8%). PD-L1 (programmed death-ligand 1) expression, when ordered (n=232), could be analysed in 94% of cases. Overall, 56.9% (33 out of 58) of patients for whom genotyping was not feasible underwent a second sampling (12 pretreatment, 21 at progression), allowing for the detection of six actionable genotypes (five EGFR, one MET). CONCLUSION: rEBUS and EMN are sensitive and safe procedures that result in limited samples, often not suitable for genotyping, highlighting the importance of integrating liquid biopsy in routine testing.