Molecular testing in central lung cancer – endobronchial ultrasound-guided transbronchial needle aspiration and circulating tumor DNA analysis compared to endobronchial forceps biopsy

Next-generation-sequencing (NGS) from circulating (ctDNA) or tissue derived tumor DNA and PD-L1 analysis are essential for the evaluation of lung cancer. The objective was to evaluate the diagnostic value of endobronchial-ultrasound-guided transbronchial-needle-aspiration (EBUS-TBNA) from tumor and lymph nodes and ctDNA analysis compared to endobronchial forceps-biopsy (FB). 30 consecutive central lung cancer subjects (10 female, median age 66, 29 current/ex-smokers) with suspected exophytic lung cancer were included. The sequence of FB and EBUS-TBNA procedures for tissue sampling was randomized. Mediastinal lymph node tissue and blood plasma was sampled additionally. PD-L1 expression level was quantified by percent of tumor cells. Mutational analysis was performed by massively parallel sequencing, library generation by adapter-ligation and target-enrichment. NGS data could be generated in 21/23 subjects (91%), 7 small-cell-lung-cancer cases were not forwarded to NGS. Comparing primary tumor FB and EBUS-TBNA samples, the accordance regarding exon-mutation-detection was 1,371/1,380 exons (99%). However, 35% of the clinical cases showed discrepant NGS results, 24% showed different PD-L1 scores. Compared to the primary tumor findings, NGS analysis from lymph node samples and ctDNA lead to discrepant findings in only 3% and 0% of cases. FB and EBUS-TBNA samples deliver discrepant results from NGS analysis in about one third of cases and from PDL1 analysis in about a quarter of cases. There is no benefit from additional routine NGS analysis from lymph node samples and ctDNA.