【Introduction】
Every year, millions of pulmonary nodules are discovered, many of which require biopsy to distinguish between malignant tumors and benign lesions. Trans-thoracic biopsy and navigational bronchoscopy are techniques used for biopsy of peripheral pulmonary nodules. Trans-thoracic biopsy is performed under the guidance of intraoperative three-dimensional CT (computed tomography) images, providing accurate diagnosis in up to 90% of cases, but it requires the needle to pass through the chest wall and pleura, resulting in up to 25% of cases developing pneumothorax. In navigational bronchoscopy, the nodules are biopsied using a catheter guided through peripheral airways based on preoperative CT images, without damaging the pleura, leading to pneumothorax in 2% of cases. However, navigational bronchoscopy has traditionally relied on intraoperative two-dimensional fluoroscopy. Previous meta-analyses have shown that its diagnostic accuracy is as low as 38%, and the aggregated result is 70%. In recent years, intraoperative three-dimensional imaging (digital tomographic synthesis and cone-beam CT) has been combined with the navigational bronchoscopy platform, and in some studies, its diagnostic accuracy is similar to that of trans-thoracic biopsy.

In order to compare the accuracy of navigated bronchoscopy and transthoracic biopsy in diagnosing patients with peripheral pulmonary nodules, we conducted the navigated endoscopy for diagnosing uncertain pulmonary nodules and transthoracic biopsy (VERITAS) trial. We hypothesized that the diagnostic accuracy of navigated bronchoscopy was not inferior to that of transthoracic biopsy.

source:Lentz RJ, et al; Interventional Pulmonary Outcomes Group. Navigational Bronchoscopy or Transthoracic Needle Biopsy for Lung Nodules. N Engl J Med. 2025;392(21):2100-2112. PMID: 40387025; PMCID: PMC12640718.


【Methods】
This study is a multicenter, randomized, parallel-group, non-inferiority trial. Patients with peripheral lung nodules of moderate or high risk (10-30 mm in size) were included and randomly assigned to receive navigational bronchoscopy or transthoracic biopsy. The primary outcome measure was the diagnostic accuracy rate (the proportion of cases with clear biopsy results and confirmed by 12-month clinical follow-up), and secondary outcome measures included surgical complications such as pneumothorax.

Navigational Bronchoscopy Group: Utilizes electromagnetic navigational bronchoscopy, integrating digital tomographic synthesis technology. The surgical plan is formulated based on CT scans taken within 3 months prior to the operation. The procedure is performed under general anesthesia by an interventional pulmonologist. During the operation, radial EBUS and rapid on-site cytological assessment can be combined. Postoperatively, immediate fluoroscopy is used to evaluate pneumothorax.

Trans-thoracic biopsy group: Under local anesthesia combined with moderate sedation or general anesthesia, a CT-guided trans-thoracic biopsy is performed by an interventional radiologist. The anesthesia method, number of biopsies, and needle selection are determined by the operator.


【Results】
Main Results
For the primary outcome measure - diagnostic accuracy, among the 119 patients in the navigational bronchoscopy group, 94 cases (79.0%) had clear biopsy results and were confirmed during the 12-month clinical follow-up; while among the 110 patients in the transthoracic biopsy group, 81 cases (73.6%) had clear biopsy results and were confirmed during the 12-month clinical follow-up (absolute difference: 5.4 percentage points; 95% confidence interval: -6.5 to 17.2; non-inferiority test p = 0.003; superiority test p = 0.17). During the 12-month clinical follow-up, in the transthoracic biopsy group, 3 cases of clear benign cases and 1 case of immediate regression case were reclassified as malignant based on subsequent examination results, with a false negative rate of 3.6%. No clear benign cases were reclassified as malignant in the navigational bronchoscopy group. The overall prevalence of malignant tumors within 12 months was 72.1% (bronchoscopy group: 74.8%, transthoracic biopsy group: 69.1%).

Secondary Results
For the secondary outcome indicators, the diagnostic rate of the navigational bronchoscopy group was 79.3%, which was confirmed during the 12-month clinical follow-up; while the diagnostic rate of the transthoracic biopsy group was 77.6%, also confirmed during the 12-month clinical follow-up (the absolute difference was 1.5 percentage points). During the 12-month clinical follow-up, 6 cases of definite benign cases and 3 cases of cases that resolved on the same day were reclassified as malignant based on the subsequent examination results in the transthoracic biopsy group. There were no cases of definite benign cases reclassified as malignant in the navigational bronchoscopy group. The overall prevalence of malignant tumors within 12 months was 76.1% (75.3% in the bronchoscopy group and 70.5% in the transthoracic biopsy group).

Safety Results
Among the 121 patients in the navigation bronchoscopy group, 6 cases (5.0%) experienced surgical complications, while in the transthoracic biopsy group, 33 cases (29.2%) experienced surgical complications (absolute risk difference was 24.2 percentage points; 95% CI, 15.0 to 35.6, Table 3). Pneumothorax was the most common, occurring in 4 cases (3.3%) in the navigation bronchoscopy group and 32 cases (28.3%) in the transthoracic biopsy group (absolute risk difference was 25.0 percentage points; 95% CI, 15.3 to 34.8).


【Discussion】
In this study, the diagnostic accuracy of navigational bronchoscopy was 79.0%, which was consistent with the results of previous studies that used the same three-dimensional imaging technology (79%-83%). The diagnostic accuracy of transthoracic biopsy was 73.6%, lower than that reported in previous non-controlled studies. This might be related to the smaller median size of nodules in this trial (15 millimeters), and the decreased diagnostic performance of transthoracic biopsy for small nodules. Moreover, previous studies had a higher risk of bias.

Experimental Advantages
Strictly screen patients to reduce referral bias; conduct recruitment in multiple centers (academic and community), ensuring the sample's representativeness and the generalizability of the results;
The independent expert group assesses the technical feasibility and reduces selection bias; the outcome assessment adopts a blind method to minimize observer bias to the greatest extent;
The follow-up was rigorous, the dropout rate was low, the definition of the primary endpoint was conservative, it conformed to clinical guidelines, and multiple sensitivity analyses verified the reliability of the results.

Limitations of the Experiment
The navigation bronchoscopy procedure is carried out by experienced pulmonologists, and the results may not be applicable to centers with less experience;
It is impossible to conceal the grouping from the operators and patients, which may lead to bias. This excluded the cases where both methods failed to reach and the nodules in the upper one-third of the lung (accounting for 6.9%);
The navigation group more frequently employs intraoperative rapid on-site cytological assessment. However, the impact of this method on diagnostic accuracy is still unclear, and there has been no assessment of its cost-effectiveness. Further research is needed to fill these gaps.


【Conclusion】
This trial has confirmed that the diagnostic accuracy of navigational bronchoscopy is not inferior to that of transthoracic biopsy, and the incidence of complications is significantly lower. It can be regarded as the preferred option for peripheral lung nodule biopsy when both methods are technically feasible.