Multimodal innovations and clinical applications of Robotic-assisted bronchoscopy in pulmonary nodule diagnosis: a review of recent advances.

Introduction
With the widespread application of low-dose computerized tomography (LDCT) screening, the detection rate of pulmonary nodules has significantly increased, especially in early lung cancer screening. Peripheral pulmonary nodules (PPNs), as common imaging findings, are critically important for accurate diagnosis. However, PPNs are usually located far from the central airways, which creates technical limitations for traditional bronchoscopic biopsy in reaching the target site and obtaining samples, resulting in a lower diagnostic success rate. Traditional CT-guided transthoracic biopsy (CTTB) is considered one of the standard methods for diagnosing PPNs, especially in cases where precise localization and relatively simple procedures are required. Literature shows that the overall diagnostic rate of CT-guided biopsy can reach over 89.5%, with high sensitivity and specificity [1]. However, the main drawback of this technique is its relatively poor accuracy for smaller nodules and increased risk of complications, such as pneumothorax and bleeding. In particular, the incidence of pneumothorax is high, and some patients even require further treatment like chest drainage, limiting its use in certain patient groups. In addition, CT-guided biopsy cannot simultaneously accomplish systematic staging of pulmonary nodules, such as mediastinal lymph node biopsy and evaluation, which typically requires additional procedural steps, prolonging the diagnostic and treatment process [1, 2]. In contrast, robotic-assisted bronchoscopy (RAB), as an emerging minimally invasive technology, integrates multi-modal techniques such as shape-sensing, electromagnetic navigation bronchoscopy (ENB), radial endobronchial ultrasound (rEBUS), and cone beam CT (CBCT), gradually demonstrating unique advantages in the diagnosis of pulmonary nodules[3, 4]. RAB can more precisely navigate to peripheral pulmonary nodules (PPNs), overcoming the limitations of traditional bronchoscopy in reaching distal nodules. Literature shows that the diagnostic success rate of RAB in complex cases is comparable to that of CT-guided percutaneous biopsy, but the complication rate is significantly lower. For example, the incidence of pneumothorax in the RAB group is only 4.4%, while the complication rate in the CT-guided biopsy group is as high as 17% [1, 2]. In addition, RAB not only provides precise biopsy but also allows for comprehensive diagnosis, including mediastinal lymph node staging, in one single procedure, offering clinicians more comprehensive pathological information when developing treatment plans.
Although CT-guided percutaneous biopsy has been widely used in the diagnosis of pulmonary nodules over the past few decades, its high risk of complications and operational limitations have led to a clinical shift towards safer and more effective alternative techniques. Through the integration of multi-modal technologies, RAB demonstrates significant advantages in both diagnostic success rates and safety. The present review will delve into the multimodal innovations of RAB technology and its latest advancements in the diagnosis of PPN, while also analyzing its prospects for clinical application.

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Shape-Sensing RAB and Comparison with Other Navigational Bronchoscopies

Shape-Sensing RAB
The introduction of Shape-Sensing Robotic-Assisted Bronchoscopy (ssRAB) provides a new approach for the diagnosis of PPN, demonstrating significant advantages. Compared with traditional bronchoscopy or CT-guided percutaneous biopsy, ssRAB uses shape-sensing technology to provide real-time feedback on the three-dimensional position of the bronchoscope, overcoming the CT-to-body divergence issue [5]. It precisely navigates to the target lesion, reducing intraoperative adjustments. Studies have shown that the lesion access success rate of ssRAB is as high as 98.7%−100%, with a diagnostic success rate of 81.7%−94.7% [6, 7]. In China, RAB technology is still in its early stages of development. In 2024, Professor Sun Jiayuan, in collaboration with three Hospitals in China, conducted an evaluation of the feasibility and safety of the ssRAB system in the Chinese population. A total of 90 patients were included in this study, with a target nodule access success rate of 100% and a diagnostic rate of 87.8%. The study demonstrated that ssRAB shows high diagnostic success and safety in the Chinese population, with very few complications—only one case of mild pneumothorax, which required no further intervention [8]. When dealing with hard-to-reach PPNs, ssRAB, through shape-sensing, real-time imaging, and stable control, overcomes the limitations of traditional bronchoscopy and significantly improves diagnostic accuracy. In terms of operational safety and postoperative complications, ssRAB has also shown significant advantages. Fielding et al. [9] demonstrated that ssRAB successfully positioned the tool in 29 patients without any occurrence of pneumothorax or severe bleeding. Similarly, no severe complications occurred in a study with a 12-month follow-up of 42 patients [10]. In 2022, a cancer center in the United States conducted an analysis of 159 PPN samples from 131 patients, showing that the overall complication rate of ssRAB was only 3%, with a pneumothorax incidence of 1.5%, most of which required no intervention [7]. By reducing common complications such as pneumothorax and bleeding, ssRAB improved diagnostic efficiency. Its minimally invasive nature also significantly shortened postoperative recovery time, greatly reducing surgical risks, and providing a safer solution for PPN diagnosis.

Comparative study of SsRAB with ENB and rEBUS
Navigational bronchoscopies include virtual navigation, ENB, and rEBUS, and RAB, as a recently introduced navigational bronchoscopy, has demonstrated significant advantages [11]. A comparative study by Yarmus et al. [12] showed that the positioning and puncture success rate of ssRAB was 80%, significantly higher than ENB’s 45% and rEBUS’s 25%. This was the first time RAB was compared with ENB and rEBUS, demonstrating that ssRAB has a clear advantage with the support of shape-sensing technology. A 2023 retrospective analysis [13] compared ssRAB and digital tomosynthesis electromagnetic navigation bronchoscopy (DT-ENB) in the biopsy of PPN. The study showed that the diagnostic rate of ssRAB in 143 peripheral pulmonary nodules was 77%, while the diagnostic rate of DT-ENB in 197 cases was 80% (P = 0.4), with no statistically significant difference between the two. The incidence of pneumothorax was 1.5% in the ssRAB group and 1.8% in the DT-ENB group (P = 0.86). The study concluded that ssRAB and DT-ENB have similar performance in terms of diagnostic efficacy and safety for PPN. A 2024 head-to-head study [14] comparing ssRAB and ENB included 116 patients with a total of 134 nodules. The results showed that for small nodules with a diameter of 0.7 to 2.0 cm, the diagnostic rate of ssRAB was 85.2%, while ENB’s was only 31.9% (P < 0.0001). For nodules with a diameter of 2.1 to 3.0 cm, ssRAB had a diagnostic rate of 100%, compared to 65.0% for ENB. Neither group experienced any major perioperative complications, nor did they report any cases of pneumothorax or require hospitalization.
From the above literature, it can be seen that ssRAB is significantly superior to ENB and rEBUS in terms of localization accuracy and diagnostic rate for PPN. While ENB performs relatively well in larger nodules, its diagnostic rate is lower for smaller nodules. rEBUS shows the poorest performance in both localization accuracy and diagnostic success, particularly when dealing with eccentric or complex lesions. Therefore, ssRAB stands out among these three techniques due to its higher precision and safety.

Multimodal Innovation of RAB
ssRAB significantly surpasses other navigational bronchoscopies in terms of localization accuracy, diagnostic rate, and safety. Therefore, if ENB, rEBUS, and CBCT technologies are combined with ssRAB for multimodal innovation in PPN diagnosis, could this further enhance diagnostic efficiency and improve operational safety? We will explore this by reviewing the latest literature in recent years.

RAB combined with ENB
ENB technology uses magnetic field positioning to provide physicians with a virtual path, guiding the bronchoscope precisely to the pulmonary nodule, thereby improving the success rate of PPN biopsy. The multimodal innovation of combining ENB with RAB can further enhance the visualization and navigation capabilities for PPN, resulting in more accurate diagnoses. A study conducted by Ekeke and his team [4] included 25 male patients, showing that the diagnostic success rate of RAB combined with ENB reached 96%, with 60% of the nodules being malignant and 16% classified as atypical or suspicious cells. The size of the nodules ranged from 0.8 to 6.9 cm. No postoperative complications were reported. The researchers concluded that RAB combined with ENB is a safe and effective tool for diagnosing pulmonary nodules, particularly excelling in the visualization and navigation of peripheral lesions. A 2023 study from the Mayo Clinic [2] showed that the diagnostic success rate of ENB combined with RAB was 87.6%, which was similar to the 88.4% of the CT-guided biopsy group, but the complication rate for RAB was only 4.4%, significantly Lower than the 17% of the CT-guided biopsy group. This indicates that the combination of RAB and ENB not only provides effective diagnostic results but also significantly reduces surgery-related complications.

RAB combined with CBCT
CBCT is an intraoperative real-time imaging technology that can confirm in real-time, through three-dimensional images, whether the biopsy tool has reached the target nodule. It helps reduce the anatomical differences caused by dynamic breathing between preoperative CT scans and real-time procedures, especially in complex cases, correcting intraoperative deviations and ensuring operational accuracy. A prospective cohort study [15] found that the navigation success rate of RAB combined with CBCT was 100%, and 83% of the nodules achieved a tissue diagnosis, with an overall diagnostic rate of 86%. Only two patients experienced mild pneumothorax after procedure, with no severe bleeding or other complications. Cumbo-Nacheli et al. [16] explored the effectiveness of combining CBCT and RAB in 20 patients with suspected malignant lung lesions. The results showed that the average time for navigation to the lesion was 9.8 min, with a navigation success rate and tool position confirmation rate of 100%. The sensitivity for malignant lesions was 86.6%, and no complications were observed. In 2023, a single-center prospective study [17] evaluated the potential radiation risk of combining ssRAB with CBCT in lung lesion biopsies. A total of 241 procedures were performed in the study, with an average Low radiation dose. The surgical diagnostic rate was 85.9%, and complications were minimal, demonstrating the safety and effectiveness of this approach. In 2024, the Mayo Clinic combined mobile CBCT with ssRAB to evaluate its diagnostic efficiency for PPNs smaller than 2 cm. Although mobile CBCT had no significant impact on overall diagnostic efficiency, it performed better in the detection of ground-glass nodules, demonstrating its potential value in handling complex subsolid nodules [18]. Shaller and co-workers [19] compared the surgical performance of traditional bronchoscopy and RAB under CBCT. The results showed that the surgery time in the RAB group was shorter, and the radiation dose was lower, attributed to its superior stability and integrated navigation capabilities.

RAB combined with rEBUS
Radial endobronchial ultrasound (rEBUS) is a real-time imaging technology that can guide biopsies and help physicians confirm tool positioning. When RAB is combined with rEBUS, the accuracy of PPN biopsy is significantly improved. A 2019 study from four medical centers in the United States [20] showed that the navigation success rate of RAB was 88.6%, with an overall diagnostic rate ranging from 69.1 to 77.0%. When combined with rEBUS, the diagnostic rate for concentric views was 81.5%, for eccentric views was 71.7%, and for cases without a view was only 26.9%. In a prospective study [21], 53 out of 54 (98.2%) patients who underwent RAB successfully obtained rEBUS imaging, with 51 (96.2%) cases successfully locating the lesion, demonstrating the validation role of rEBUS in RAB navigation. A single-center prospective study [22] in China included 30 patients, and rEBUS successfully obtained images of 29 nodules, with 21 nodules showing concentric images, further confirming the precise localization capability of RAB combined with rEBUS. A multicenter prospective study by Reisenauer’s team [23] showed that, in 270 nodules, 89.5% of the cases successfully confirmed the location using RAB combined with rEBUS. In a study at the University of Chicago Medical Center [24], a 12-month follow-up was conducted to evaluate factors affecting the diagnostic accuracy of RAB, and the overall diagnostic accuracy was found to be 77%. rEBUS imaging had a significant impact on diagnostic accuracy, with a diagnostic rate of 85% for concentric views, 84% for eccentric views, and only 38% when no rEBUS image was obtained. Styrvoky et al. [3] specifically evaluated the effectiveness of ssRAB combined with rEBUS and CBCT in PPN biopsy. The study included 200 patients involving 209 PPNs. All patients underwent navigation and localization using both rEBUS and CBCT. The results showed that the diagnostic accuracy of ssRAB combined with rEBUS and CBCT was 91.4%, with a sensitivity of 87.3% and specificity of 98.7%. The complication rate was Low, with a pneumothorax incidence of 1%, and only 0.5% of the cases required chest tube intervention. This study is the first to evaluate the combination of RAB with both rEBUS and CBCT, and the diagnostic accuracy was significantly higher than that of techniques using these modalities separately [18, 20].

RAB combined with needle-based confocal laser endomicroscopy
In addition to the aforementioned multi-modal imaging technologies, a literature [25] reports that RAB can also be combined with needle-based confocal laser endomicroscopy (nCLE) to improve diagnostic accuracy. nCLE is a laser-based in vivo imaging technology that provides real-time microscopic images through a micro-probe. This technology allows needle-guided operators to accurately locate lesions and perform biopsies in complex peripheral nodule regions. In this study [25], 95% of the patients successfully obtained high-quality nCLE images, and 45% of the patients were repositioned through nCLE guidance due to needle misplacement. The overall diagnostic success rate was 80%. No patients experienced complications related to nCLE or fluorescein during the procedure. This study indicated that nCLE could provide real-time needle positioning feedback for small and hard-to-reach PPNs, effectively reducing the risk of sampling failure. Compared to bronchoscopic biopsy relying solely on CT or EBUS, nCLE demonstrated potential in optimizing the sampling area and improving diagnostic success rates, offering new insights for future diagnosis.
The combination of shape-sensing RAB with multi-modal imaging technologies such as ENB, rEBUS, and CBCT significantly improves the diagnostic accuracy of PPN biopsy while reducing the incidence of surgical complications. These studies suggest that RAB has unique advantages in diagnosing complex pulmonary nodules and is expected to become a standard diagnostic method in the future.

Role of Transbronchial Crybiopsy (TBCB) in RAB for PPN biopsy
Although multiple studies have shown that RAB, through shape-sensing and multi-modal imaging technologies, can significantly improve the diagnostic rate of PPN biopsy after precise localization, the forceps biopsy yield small sample sizes, particularly when rEBUS shows eccentric views, resulting in lower success rates of biopsy tools. Moreover, traditional biopsy tools are inadequate for molecular biological analysis of tumor samples. In recent years, researchers have applied transbronchial cryobiopsy (TBCB) in RAB for PPN biopsy, further enhancing diagnostic capabilities. A study [26] explored the diagnostic efficacy and safety of a 1.1 mm cryoprobe combined with ssRAB in PPN. The results showed that the positive rate of needle aspiration was 31.5%, 77.8% for forceps biopsy, while the diagnostic rate of TBCB was as high as 97.2%. All tumor specimens obtained from TBCB successfully underwent molecular marker analysis, significantly outperforming other biopsy methods. In tissue quality assessment, the diagnostic tissue yield from TBCB samples was nearly twice that of forceps biopsy and more than 10 times that of needle aspiration. A 2023 study [27] evaluated the diagnostic efficacy, safety, and feasibility of using the RAB system combined with a 1.1 mm small cryoprobe for TBCB in PPN. The results showed that TBCB provided a diagnostic incremental effect of 20% for eccentric or adjacent lesions and 12% for concentric lesions. Compared with forceps biopsy, TBCB demonstrated superior incremental diagnostic efficiency (70.6% vs. 53.4%). The complication rate was Low, with a pneumothorax incidence of 5% (3 cases), all successfully managed, and a bleeding rate of 6.9%, all classified as grade 2 bleeding. Overall, the cryoprobe has a 360-degree full-range sampling capability, allowing for more and higher-quality tissue samples, particularly excelling in diagnosing eccentric or extrabronchial lesions that are difficult to diagnose with traditional tools. The diagnostic rate is higher, and it also shows significant advantages in molecular marker analysis with reliable safety.

Limitations of RAB
Although the multimodal innovations of RAB in PPN diagnosis have shown great clinical potential, certain limitations still exist. Firstly, most current studies are based on single-center or retrospective data, which may affect the generalizability of their results. Secondly, RAB’s real-time three-dimensional imaging capabilities are not yet as advanced as ENB technology, such as digital tomosynthesis-corrected electromagnetic navigation bronchoscopy, which increases procedural accuracy by correcting lesion positioning with real-time imaging. Additionally, RAB’s high equipment cost, lack of tactile feedback for the operator, the need for a learning curve [28], longer procedural times, and the risk of severe complications such as bleeding or pneumothorax in inexperienced hands, all limit its widespread use.

Conclusion
RAB, through the combination of shape-sensing technology and multi-modal imaging navigation, has shown great potential and significant clinical application prospects in the diagnosis of pulmonary nodules, especially peripheral small nodules [29]. Compared with traditional EBN and rEBUS, RAB excels in localization accuracy, operational stability, and diagnostic success rate. This high-precision localization and stability allow RAB to effectively reduce complications such as pneumothorax and bleeding, further enhancing its safety and feasibility in clinical practice.
Future research directions should focus on prospective, multicenter large-scale clinical trials to further verify the applicability of RAB in different patient groups and complex cases [30]. At the same time, combining other technologies such as rEBUS, ENB, and CBCT for multi-modal approaches may further improve diagnostic accuracy and procedural safety. For patients with poor physical condition who are unable to undergo surgery, bronchoscopic ablation (such as radiofrequency or microwave) of PPNs can be performed simultaneously during RAB procedures [31], enabling RAB to facilitate both diagnosis and treatment concurrently.
Overall, RAB technology is expected to replace or complement traditional bronchoscopy and CT-guided biopsy in future pulmonary nodule diagnoses, becoming a standard diagnostic method. As more prospective, multicenter clinical research results accumulate, the clinical application prospects of RAB will become broader, potentially driving further optimization of early diagnosis and treatment for pulmonary nodules.