The role of EBUS-TBNA in lung cancer restaging and mutation analysis

In recent years, several molecules targeting specific genetic aberrations were released for the treatment of patients affected by locally advanced and metastatic non-small cell lung cancer (NSCLC), leading to an improvement in survival. Moreover, inhibitors of PD-1 and PD-L1 immune checkpoints showed to improve survival, and they are now indicated as first-line treatment in selected patients. Hence, the collection of adequate samples for diagnosis, staging, genotyping and immunohistochemical analysis is a fundamental step in NSCLC treatment planning. When feasible, EBUS-TBNA is suggested as the first-choice diagnostic tool by most of the guidelines. Several studies demonstrated that mutation analysis is viable with high levels of accuracy on both cytological and histological samples obtained by EBUS-TBNA. No technical factor (type of needle, number of passes, use of rapid-on-site-examination, material processing, detection method) has been identified as uniquely influencing the diagnostic yield of molecular analysis. EBUS-TBNA demonstrated to be useful for the restaging of patients affected by locally advanced NSCLC who underwent induction chemotherapy or chemo-radiotherapy, as well as in those who show acquired resistance to targeted therapy and immunotherapy. Nevertheless, most authors agree that a high number of false negative results should be expected due to the likely presence of necrosis and fibrosis induced by neoadjuvant treatments. Therefore, in case of EBUS-TBNA negative sample, pathologic confirmation by surgical biopsy is recommended for the planning of definitive treatment. As suggested by a few preliminary experiences, a wide application of next-generation sequencing (NGS) on EBUS-TBNA specimens will lead to the development of better tailored treatments with simultaneous identification of a large number of gene alterations on a single sample at the time of diagnosis.