Is Biopsy of Contralateral Hilar N3 Lymph Nodes With Negative PET-CT Scan Findings Necessary When Performing Endobronchial Ultrasound Staging?

BACKGROUND: Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. RESEARCH QUESTION: What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? STUDY DESIGN AND METHODS: This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%. RESULTS: Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P < .001). Patients with positive PET scan results of the mediastinal N3 nodes were at higher risk of having occult hilar N3 nodal metastasis (P = .003), found in 3 of 46 patients (6.5%; 95% CI, 1.4%-17.9%) with positive PET scan results of the mediastinal N3 nodes. INTERPRETATION: When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.

Sensitivity of Radial Endobronchial Ultrasound-Guided Bronchoscopy for Lung Cancer in Patients With Peripheral Pulmonary Lesions: An Updated Meta-analysis.

BACKGROUND: Registry trials have found radial endobronchial ultrasound (r-EBUS) sensitivity to vary between institutions, suggesting that in clinical practice, r-EBUS sensitivity may be lower than reported in clinical trials. We performed a meta-analysis to update the estimates of r-EBUS sensitivity and to explore factors contributing to heterogeneity of results. METHODS: A systematic review using PubMed was performed through July 2018 to determine the sensitivity of r-EBUS for lung cancer, and to construct a summary receiver operating characteristic curve. The DerSimonian and Laird method was used to weight results. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. Study quality was assessed using the QUADAS tool, and publication bias was tested using funnel plots. RESULTS: Fifty-one studies with a total of 7,601 patients were included. r-EBUS pooled sensitivity was 0.72 (95% CI, 0.70-0.75), and area under the sROC curve was 0.96 (95% CI, 0.94-0.97). Significant heterogeneity was observed (I2 = 76%; heterogeneity P < .01). We failed to demonstrate an association between sensitivity and air bronchus sign, average nodule size, use of fluoroscopy, virtual bronchoscopy, guide sheath, cancer prevalence, multicenter status, or consecutive enrollment. Rapid onsite cytology was associated with increased sensitivity (P = .01). The pooled pneumothorax rate was 0.7% (95% CI, 0.3%-1.1%). Funnel plots were asymmetrical, demonstrating sample size-related effects and possible publication bias. CONCLUSIONS: r-EBUS has an excellent safety profile, but there is significant between-study heterogeneity. Sample size-related effects and possibly publication bias have led to overly optimistic estimates of the sensitivity of r-EBUS.