proportion of accessible lymph node stations with the combined approach compared to CP-EBUS-TBNA alone (85% vs. 79%; p = 0.015) [72]. The current literature supports the combined use of combined CP-EBUS-TBNA and EUS-FNA, and is likely benefcial in situations when it will change the outcome provided by CP-EBUS-TBNA alone, but limitations in operator experience, credentialing, and equipment restrict generalizability.

CP-EBUS for Restaging NSCLC After Neoadjuvant Chemotherapy

Advancements in chemoimmunotherapy have changed the management approach to patients with stage IIIA-N2 NSCLC. Previously this group of patients was labeled to have unresectable lung cancer and defnitive chemoradiation was the treatment of choice. Now the use of induction chemotherapy and neoadjuvant therapy has expanded the options for certain patients in this group to include surgery pending the results of a mediastinal restaging [73]. This management approach continues to be controversial, but the literature supports that induction chemotherapy and neoadjuvant chemotherapy prior to surgery may improve overall survival in this group of patients [74, 75]. The optimal method for mediastinal restaging is yet to be determined, but CP-EBUS-TBNA remains an acceptable option due to the low sensitivity and negative predictive value of PET/CT, and the technical diffculty encountered when performing mediastinoscopy following recent chemoradiation. To assess adequacy of CP-EBUS-TBNA for restaging, Herth et al. in 2008 enrolled 124 patients with stage IIIA-N2 NSCLC who had shown a positive response or stable disease on CT after undergoing neoadjuvant chemotherapy prior to undergoing surgical resection with lymph node dissection. All patients underwent CP-EBUS-TBNA restaging with 89 patients (72%) found to have residual N2 disease and 35 patients (28%) with no residual disease. Thoracotomy confrmed the 89 patients with residual N2 disease but discovered

an additional 28 of the 35 patients with no residual disease on CP-EBUS-TBNA had residual N2 disease present. CP-EBUS-TBNA for residual N2 disease after neoadjuvant chemotherapy for NSCLC demonstrated a sensitivity of 76%, specifcity of 100%, negative predictive value of 20%, and an overall diagnostic accuracy of 77%. Of the 28 false negative N2 lymph nodes, 91% were sampled by CP-EBUS and the failure to diagnose residual malignancy was attributed to sampling error and changes induced within the lymph following neoadjuvant therapy [76]. Although these results do not support the use of CP-EBUS-­ TBNA to rule out residual N2 disease following neoadjuvant therapy, the ability to identify residual N2 disease and therefore potentially prevent a patient from undergoing an unnecessary surgery makes it an important part of the management approach.

CP-EBUS forBiomarker Testing

Since the advent of immunotherapy and targeted therapy for NSCLC, the type of tissue and optimal modality to obtain that tissue has been vigorously discussed. CP-EBUS-TBNA has been instrumental in the diagnosis and staging of NSCLC, but its ability to provide adequate samples for full molecular testing has been debated. Currently, clinical guidelines support obtaining malignant tissue for the identifcation of several targetable biomarkers which can optimally direct treatment plans in patients with NSCLC [77, 78]. A recent study published by Martin-Deleon evaluated 72 patients with suspected stage III or IV lung cancer who underwent CP-EBUS-TBNA for mediastinal staging resulting in 42 patients diagnosed with NSCLC. Among the cytological samples provided by CP-EBUS-TBNA, next-­ generation sequencing (NGS) genotyped 92.9%, nCounter genotyped 95.2%, and 100% of the samples were adequate for immunohistochemistry testing [79]. These fndings and previous studies support the use of CP-EBUS-TBNA as a reasonable modality to obtain material for NSCLC biomarker testing [80–82].