Peripheral pulmonary lesions (PPLs), typically small and located in distal airways, pose challenges for early lung cancer diagnosis due to their peripheral location and limited accessibility with conventional bronchoscopy (1). Although advances in imaging and biopsy procedures such as radial probe endobronchial ultrasound have improved detection rates, achieving a diagnostic sensitivity ranging between 69% to 73%, a substantial proportion of PPLs remain undiagnosed.

Virtual bronchoscopic navigation (VBN) has emerged as a valuable tool to overcome the challenges of accessing peripheral pulmonary lesions by using pre-acquired computed tomography (CT) imaging to create virtual pathways that guide the bronchoscope to hard-to-reach areas, thereby improving diagnostic accuracy—with an overall yield of 73.8%, including 67.4% for lesions ≤2 cm—and reducing the need for more invasive procedures (2–4). Diagnostic accuracy improves to 80.4 – 83.6% when VBN is combined with endobronchial ultrasound (EBUS), which enhances visualization of the lesion and surrounding structures, enabling more precise localization (5, 6). However, diagnosing some PPLs remains challenging in the absence of bronchus sign.

The bronchoscopic trans-parenchymal nodule access (BTPNA) is an advanced procedure facilitated by Archimedes™ navigation system, which have potential to fix these problems. Unlike conventional approaches that navigate through the pre-existed airways, BTPNA directly accesses lung parenchyma through newly created pathway, allowing accurate biopsy of PPLs (7–9). It processes pre-acquired CT scans to identify the optimal point of entry (POE) in the airway and delineates a safe, avascular path to the target lesion. During the procedure, this virtual pathway assists in guiding the bronchoscope, while real-time fluoroscopy overlays live imaging with the pre-planned route to ensure precise navigation (10, 11). By integrating these advanced techniques, the Archimedes system provides a minimally invasive method, that may be an alternative way to CT-guide biopsy or surgical methods for diagnosing PPLs without bronchus sign.

This study examines the procedural and diagnostic details of our experience with 10 cases of PPLs at a tertiary medical center, aiming to present the safety and diagnostic yield of BTPNA guided by the Archimedes navigation system in patients with PPLs without bronchus sign. The findings will contribute to the growing body of evidence supporting the use of BTPNA for the early and accurate diagnosis of PPLs.

This study demonstrates the safety and effectiveness of the Archimedes™ navigation system via BTPNA, achieving a 70% diagnostic yield for small peripheral pulmonary lesions (PPLs) under 2 cm without bronchial signs. Among the 10 patients evaluated, no complications were reported, further supporting the procedure’s safety. These results highlight the potential of BTPNA to improve diagnostic accuracy for small, distal PPLs while reducing the need for invasive surgical biopsies and associated risks. Compared with previous vital studies (7, 11, 12), this study especially included the patients with smallest nodule and no bronchial sign for the future integration of BTPNA and radiofrequency ablation (RFA) to provide a seamless solution for non-invasive diagnosis and treatment.

Conventional bronchoscopic biopsy methods have markedly lower diagnostic yields in peripheral lesions lacking an airway path (bronchus sign), often below 30% (13). This limitation arises because standard techniques (radial EBUS or navigation-guided transbronchial biopsy) struggle to reach nodules without a guiding bronchus. BTPNA was specifically developed to overcome this issue by creating a direct transparenchymal access route to the nodule under virtual navigation guidance (10, 13). Emerging high-level evidence demonstrates that BTPNA can substantially improve diagnostic outcomes in these challenging cases. Herth et al. first reported an ~82% diagnostic yield using an Archimedes-guided BTPNA approach in a pioneering trial (7). In our present study, the overall diagnostic yield was 70% with a mean nodule lesion size of 13.9 mm and a median tunnel length range of 55.0 - 61.5 mm.

Besides, the NAVIGATOR study by Hiddinga et al. (12) reported an overall diagnostic yield of 77%, based on a mixed approach that included airway, tunnel, and combined navigation paths. However, for lesions approached solely via the tunnel path specifically, the diagnostic yield was 62% (8 out of 13 cases), with a median nodule size of 25 mm. In comparison, the longer tunnel lengths and smaller mean nodule size in our study suggest an enhanced ability to access deeper, more peripheral, and smaller lesions. In the multicenter study by Sun et al. (11), a biopsy yield of 86.3% was reported across 51 lesions sampled using BTPNA, with a mean tunnel length of 3.3 cm and a mean lesion size of 2.4 cm. While their reported diagnostic yield is higher, it’s worth noting that our study focused on smaller and more technically challenging lesions. Despite these differences, we were still able to achieve a comparable level of diagnostic performance.

In the present study, no complications were observed (0%), highlighting the favorable safety profile and feasibility of the BTPNA procedure. This finding is consistent with several previous studies that have also reported low complication rates for VBN-guided techniques.

For instance, a multicenter study by Sun et al. (11) involving 114 patients who underwent lesion sampling with the Archimedes™ system reported a mean lesion size of 24 mm. Of the 51 lesions sampled using BTPNA, and the remaining with guided TBNA, only two cases of pneumothorax (1.9%) and one case of mild bleeding (1.0%) occurred—none requiring chest tube placement. Although complications were not specifically attributed to either technique, the authors emphasized the safety of BTPNA, even for lesions requiring longer tunnel access.

An earlier study by Harzheim et al. (8) also explored the risks associated with BTPNA. While no significant intraprocedural adverse events occurred, two patients (33.3%) developed postprocedural pneumothorax, one of whom required chest tube drainage. However, these cases involved nodules located very close to the pleura (1 mm and 9 mm, respectively), highlighting the importance of preprocedural planning and patient selection, especially when dealing with subpleural lesions.

Additionally, Verga et al. (14) evaluated 96 patients with advanced lung disease undergoing VBN-guided sampling. The mean lesion size was 23 mm, with BTPNA performed in only three cases. Most patients underwent conventional VBN-guided transbronchial approaches in combination with radial EBUS and fluoroscopy. The overall complication rate was 7%, including 1% pneumothorax, 3% significant bleeding, and 3% respiratory failure.

In contrast, traditional CT-guided transthoracic needle aspiration is associated with higher risks, including pneumothorax rates of approximately 15 – 25% and chest tube placement in 4 – 6% of cases (15). BTPNA may offer a less invasive alternative with fewer complications.

BTPNA may serve as a critical platform for advancing novel bronchoscopic therapies aimed at treating peripheral lung lesions (PPLs), including RFA, microwave ablation, bronchoscopic thermal vapor ablation (BTVA), and cryotherapy. Changhao Zhong and colleagues reported promising one-year results for transbronchial RFA, with a complete ablation rate of 90.48% and an intrapulmonary progression-free survival rate of 88.89% (16). Additionally, Daniel P. Steinfort and his team demonstrated the efficacy of BTVA in six patients, observing up to 99% tumor necrosis within the ablation zones (17). Looking forward, BTPNA—particularly when integrated with other ablation strategies—holds strong potential as a central platform in the treatment of PPLs.

This study has several limitations. The small sample size and single-center design restrict the generalizability of the findings to broader patient populations. Additionally, potential selection bias—such as the exclusion of high-risk patients with severe COPD, pulmonary fibrosis, or coagulopathy—may limit the applicability of the results to real-world clinical scenarios involving peripheral lung lesions (PPLs).

The Archimedes™ navigation system-guided BTPNA has demonstrated promise as a minimally invasive approach for diagnosing small and difficult-to-access peripheral pulmonary lesions (PPLs) without bronchus signs, achieving a 70% diagnostic yield without any reported complications in the current study. However, larger prospective multicenter trials are needed to confirm these findings, further establish the system’s efficacy, enhance safety protocols, and expand its clinical applicability.