Clinical UM Guideline

This document addresses the use of navigational bronchoscopy (NB) devices as an aid in accessing peripheral lung lesions and masses, which may be inaccessible by standard bronchoscopy. This document includes the following techniques:

• Electromagnetic navigational bronchoscopy (ENB)
• Artificial Intelligence (AI) Tomography with Augmented Fluoroscopic Guidance 
• Robotic assisted bronchoscopy

Navigational bronchoscopy has also been used as a means of placing fiducial markers for surgical and radiological procedures.

Medically Necessary:

Navigational bronchoscopy is considered medically necessary for the following indications (A or B):

1. In individuals for whom nonsurgical biopsy is indicated when both transthoracic needle biopsy and conventional bronchoscopy are considered inadequate to accomplish the diagnostic or interventional objective; or
2. For the pre-treatment placement of fiducial markers within lung tumor(s).

Not Medically Necessary:

Navigational bronchoscopy is considered not medically necessary for all other indications.

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure code listed above when criteria are not met and for all other indications.

In 2023, lung cancer will be diagnosed in approximately 238,340individuals in the United States and will cause an estimated 127,070deaths (ACS, 2023). Lung cancer screening using low-dose CT of the chest is recommended in individuals considered at high risk (National Comprehensive Cancer Network [NCCN], V1.2024). Over 25% of the computed tomography (CT) scans in the high-risk population will be abnormal. These screening CT chest scans can result in a high proportion of false-positive peripheral pulmonary lesions, up to 96.4% (McGuire, 2020). While early detection is integral to improved outcomes, false positive results can result in over-diagnosis and increased testing, including invasive testing. Invasive testing increases the risk of complications such as pneumothorax.

Individuals with suspect nodules can undergo biopsy using several techniques, depending upon nodule location. Central masses may typically be biopsied by bronchoscopy or mediastinoscopy. Nodules which are located in the periphery of the lungs account for more than 70% of potential malignant lesions (Stone, 2022). Peripheral nodules may benefit from navigational bronchoscopy, radial endobronchial ultrasound (EBUS), or transthoracic needle aspiration (TTNA) (NCCN, V3.2023).

Contraindications to bronchoscopy or TTNA

Surgical biopsy is recommended in individuals with resectable nodules who are a low to intermediate surgical risk when there is a high clinical suspicion for cancer. This approach potentially avoids the need for separate diagnostic and therapeutic procedures and minimizes the time to treatment. However, the population with suspicious nodules are frequently older with underlying respiratory disorders, and more likely to be high risk surgical candidates (Seijo, 2016). Established biopsy techniques such as bronchoscopy and TTNA are used when the surgical approach is not appropriate. These techniques are not adequate in all instances and navigational bronchoscopy may be a more appropriate choice when conventional bronchoscopy or TTNA would not be an adequate diagnostic technique.

The utility of conventional bronchoscopy is dependent on the size and location of the nodules. In small peripheral lesions, conventional bronchoscopy is associated with poor diagnostic yields (Seijo, 2016). The American College of Chest Physicians (ACCP) guidelines (2013) do not recommend conventional bronchoscopy for small pulmonary nodules unless a bronchus sign is present. With increased screening and improved imaging available, smaller nodules are being identified. The overall sensitively of conventional bronchoscopy decreases as the size of the nodules decrease (Seijo, 2016).

TTNA has been shown to have a high sensitivity, but there is an elevated risk of adverse events such as pneumothorax or pulmonary hemorrhage (Chockalingam, 2015; Hong, 2021). The risks associated with TTNA increase in older individuals, individuals with a significant past medical history, larger lesions or who may be uncooperative during the procedure. The majority of TTNA relative contraindications are related to respiratory comorbidities such as pulmonary hypertension, emphysematous disease and chronic obstructive pulmonary disease (COPD). Large bullae can result in a post-procedure pneumothorax (Chockalingam, 2015). Nodule size and location are factors which affect the risks associated with TTNA. In nodules less than 20mm, the risk of complications is 11 greater than larger nodules. The complication risk increases as the distance from the nodule to the pleural surface increases (Seijo, 2016).

The 2013 ACCP Evidence Based Guidelines recommend bronchoscopy for individuals with central lesions. Peripheral pulmonary lesions (PPLs), which can be defined as “lesions surrounded by  lesions surrounded by normal pulmonary parenchyma without any computed tomography evidence of endobronchial abnormalities” are typically not visible on bronchoscopy (Jiang, 2020). For individuals with peripheral lung lesions which are difficult to reach with conventional bronchoscopy, the ACCP recommends electromagnetic navigation guidance if available and TTNA is ENB is not available. The British Thoracic society guideline on the management of pulmonary nodules (Callister, 2015) notes the following evidence statement:

Diagnostic yield of bronchoscopy may be increased by the use of fluoroscopy, electromagnetic navigation and radial endobronchial ultrasound and in the presence of a CT bronchus sign. However, yield remains relatively low for lesions <2 cm in the peripheral third of the lung.

Grade D: Evidence level 3 or 4 or Extrapolated evidence from studies rated as 2+
Evidence level 3: Non-analytical studies—for example, case reports, case series

In a retrospective cohort analysis, Vachani and colleagues (2022) reported on population-based estimates regarding complications and risk factors associated with transthoracic needle biopsy (TTNB). Individuals who underwent a stand-alone TTNB in 2017 or 2018 (n=16971) were included. Procedure related complications (pneumothorax, hemorrhage, and air embolism) were analyzed to estimate the association of these complications with setting of care and individual demographic and clinical characteristics. Within 3 days post-procedure, 25.8%  experienced a complication (pneumothorax 23.3%, hemorrhage 3.6%, and air embolism 0.02%). Inpatient status and a history of COPD, a previous lung cancer screening or bronchoscopy or oral anticoagulants or antiplatelet therapy were associated with an increased risk of pneumothorax or hemorrhage.

In summary, transthoracic needle biopsy and conventional bronchoscopy may be considered inadequate to accomplish their intended diagnostic or interventional objective in certain individuals based on a number of considerations. These considerations include the anatomic location of the nodule/lesion or individual risk status. ENB may be more appropriate for lesions that are located in the lung periphery and in individuals who are at high risk for complications associated with transthoracic needle biopsy and/or conventional bronchoscopy (for example, in individuals who are at high risk of pneumothorax, or when lesions have surrounding emphysema).

Lung Biopsy

ENB

ENB devices are used in conjunction with standard bronchoscopy and are not FDA approved as stand-alone surgical devices/procedures. ENB is used to guide the bronchoscope and bronchial tool to an intended target located in or adjacent to the bronchial tree on a path indicated by CT scan and visualizes the target and the interior of the tree. The ENB devices include sensors placed on the chest to provide real time navigation during the procedure.

The U.S. Food and Drug Administration (FDA) has approved two devices. The SuperDimension™ Navigation System (Medtronic, Minneapolis, MN) received 510(k) clearance from the U.S. Food and Drug Administration (FDA) in 2008. The system is intended to display images of the tracheobronchial tree, aiding the physician in guiding endoscopic tools or catheters in the pulmonary tract for diagnostic purposes or to enable marker placement within soft lung tissue. The second device, SpiN Drive® System (Olympus Corporation of the America, Center Valley, PA), is also known as the ig4™ EndoBronchial System which received FDA clearance in December 2009.

In 2017, Khandar and colleagues published the interim, 1-month results of the NAVIGATE study, a prospective, single arm, multicenter study of individuals who underwent ENB. The NAVIGATE study was developed in order to address concerns about the clinical utility of ENB outside of the research setting. Participants included individuals undergoing ENB procedures for lung lesion biopsy (n=964), fiducial marker placement (n=210), pleural dye marking (n=17), and/or lymph node biopsy (n=334). The majority of the lesions were in the peripheral/middle lung thirds (92.7%). The primary endpoint was index ENB-related pneumothorax rated grade ≥ 2, as it is applicable to all ENB procedures. At the 12- and 24-month follow-ups, the diagnostic yield of the index ENB procedure will be calculated as the proportion of individuals with a definitive diagnosis. One month follow-up data was obtained on 93.3% of the first 1000 primary cohort participants. Pneumothorax of grade ≥ 2 related to the ENB procedure was reported in 3.2% (32/1000) of the group. Pneumothorax of any grade was reported in 4.9% (49/1000) of the cases. There were 23 individuals who died by the 1-month follow-up, no deaths were considered to be a direct result of the ENB procedure. Tissue biopsy was successful in 94.4% (910/1000) in those individuals who were diagnosed with primary lung adenocarcinoma or non-small-cell lung cancer NOS and molecular genetic testing was attempted; there was adequate tissue in 56/70 (80%). The onsite pathology sample assessments reported non-malignancy in 372/910 (40.9%) cases, malignancy in 45.8% (417/910) cases and inconclusive results in an additional 13.3% (121/910). Fiducial markers were placed in 210 individuals with operators reporting accurate placement in 208/210 (99.0%) cases. A total of eight (3.8%) grade ≥ 2 pneumothoraxes were reported.

In 2019, the 1-year results of the NAVIGATE study were reported by Folch and colleagues. The purpose of 12- month follow-up was to determine the true diagnosis (malignant or nonmalignant). The study defined initial negative results as results that were diagnostic of a nonmalignant condition or indeterminate results. At 12 months post-procedure, cases reporting subsequent diagnostic tests confirming a nonmalignant diagnosis or without lesion progression on radiographic follow-up were considered true-negative. Cases categorized as false-negative included those cases in which follow-up diagnostics revealed malignancy, lesion growth was noted on repeat diagnostic testing, death due to lung cancer within 12 months, treatment without a confirmed diagnosis or new diagnoses of cancer in the lung from any site. A total of 1215 individuals underwent an ENB aided procedure. A 12-month follow-up was completed on 80.3% (976/1215) of the participants. In those individuals who underwent lung lesion biopsy (n=1157), tissue was obtained in 94.4% of the cases (n=1092). Malignancy was diagnosed in 44.3% (484/1092) of the cases and was negative in 55.7% (608/1092) of the cases. At 12 months, the diagnostic yield was 72.9%. Sensitivity for malignancy was 68.8% (range: 59.9%-68.8%); the reported negative predictive value (NPV) was 56.3% (range: 46.7%-63.8%). The specificity and positive predictive value (PPV) were reported as 100% and the NPV was calculated at 56%.

Folch and associates (2022) reported on the 24-month results of NAVIGATE participants. The majority of the  individuals underwent ENB for lung lesion biopsy (n=1329 or 95.7%). A total of 1260/1329 (94.8%) of individuals completed the ENB procedure and tissue was obtained. A result positive for malignancy was obtained in 537/1260 (42.6%) of the time and in 57.4% (723/1260) of cases a negative result was obtained. At 24 months, the global diagnostic yield was 67.8% the sensitivity analysis ranged from 61.9% to 70.7%, based upon the 117 samples which remained indeterminate. ENB was associated with a low complication risk, with a reported 3.2% rate of pneumothorax which required intervention or hospitalization. The authors summarize that although other studies have reported higher diagnostic yields, the NAVIGATE study is designed as a pragmatic study to evaluate outcomes in the real world.

McGuire and associates (2020) determined the comparative diagnostic accuracy, sensitivity, and negative predictive value for radial-EBUS (R-EBUS) and ENB in sampling peripheral pulmonary lesions (PPLs). A total of 17 ENB and 24 R-EBUS studies were included with 2097 participants in the R-EBUS group and 1107 participants in the ENB group. Both technologies report a high proportion of successful localization (90.2% versus 98.2%, respectively) with similar diagnostic accuracy for malignancy (72.4% versus 76.4%, respectively).

In 2022, Zheng and colleagues reported the results of a prospective, multicenter, randomized controlled trial to compare the diagnostic value of EBUS used with an ENB system versus EBUS alone. Data from a total of 385 individuals with peripheral pulmonary nodules (PPN) suspected to be malignant were analyzed, 193 in the ENB-EBUS group and 192 in the EBUS group. The diagnostic yields were 82.9% (95% confidence interval [CI], 77.6–88.2%) in the ENB-EBUS group and 73.4% (95% CI, 67.2–79.7%) in the EBUS group, a difference that was statistically significant. The authors concluded that combining ENB with EBUS improved the ability to locate PPN and the diagnostic yield compared to EBUS alone.

ENB with real-time imaging

In an attempt to address the lack of real-time imaging, a limitation associated with ENB, digital tomosynthesis using conventional C-arm, or fluoroscopic ENB (F-ENB), was introduced as part of a software upgrade of the superDimension package. The ILLUMINSITE™ platform has been used as a means to mitigate CT body divergence, which is the difference between the location of the nodule on the pre-procedure CT scan and the location during the procedure. In addition to the total IV anesthesia associated with ENB, F-ENB requires neuromuscular blockade in order to capture the tomosynthesis images. The use of adjunctive real-time imaging with ENB can improve the process of obtaining diagnostic tissue from lung nodules by overcoming the limitations of CT scan to body divergence (Aboudara, 2020; Avasarala, 2022; Podder, 2022; Pritchett, 2018).

Artificial Intelligence (AI) Tomography with Augmented Fluoroscopic Guidance 

In 2018, the LungVision^™ System (Body Vision Medical Inc., New York, NY) received FDA clearance as a tool, used with standard bronchoscopic instruments, to guide the instruments to the target area within the respiratory system. The approval is based upon a predicate guide sheath. The LungVision system provides guidance during a bronchoscopy via multi-modal image fusion of preoperative CT and interoperative fluoroscopy. This allows real-time augmented endobronchial fluoroscopic navigation and guidance. The initial LungVision device included multi-image fusion capabilities. LungVision’s second generation system incorporated AI algorithms, C-arm based tomography (CABT) technology and navigation tool integration into the system (Pertzov, 2021). Studies support results comparable to other forms of navigational bronchoscopy (Cicenia, 2021; Pertzov, 2018).

Robotic assisted bronchoscopy

The Monarch^® Platform (Auris Health Inc., Redwood City, CA) received FDA clearance on March 22, 2018. The system includes 2 robotic arms and the electronic systems used to operate the arms. Navigational support is provided by ENB using a CT scan obtained within 2 weeks pre-procedure. A flexible bronchoscopy is first performed to confirm the absence of endobronchial disease and provide topical anesthesia. The scope is then advanced using direct visualization, ENB and fluoroscopic guidance. Once the targeted location is reached, an R-EBUS probe is inserted into the working channel to view the area. Following R-EBUS visualization, TBNA is used to obtain samples from the targeted lesions (Chen, 2020).

The Ion^™ Endoluminal System (Intuitive Surgical, Inc, Sunnyvale, CA) received clearance by the FDA in February 2019. The Ion System uses a CT scan and proprietary software to generate a 3D visualization of the airway to identify the nodule and map and save a pathway to the targeted nodule, which is loaded into the controller. This preloaded pathway and real-time vision using a fiberoptic shape sensor is used to provide location information while accessing the nodule. The catheter is locked in place once the nodule is accessed and a needle is advanced through the catheter to obtain the sample.

The BENEFIT study, a prospective, multicenter pilot and feasibility study evaluated the use of a robotic bronchoscopic system in accessing and obtaining peripheral pulmonary lesions (Chen, 2020). Individuals with peripheral pulmonary lesions 1 to 5 cm in size with no evidence of mediastinal or hilar lymph node disease were included (n=54). The primary efficacy point was confirmation of lesion localization with R-EBUS. Lesion localization with R-EBUS was confirmed in 96.2 % (51/53) of the cases. The diagnostic yield at 12-month follow-up was reported as 74.1% (40/54). Pneumothorax was reported in 3.7% (2/54) of the cases, 1 of which required tube thoracostomy.

Fiducial Marker (FM) Placement or Pleural Dye Marking of Lung Nodule

FM are used as a means of motion management during gated stereotactic body radiation therapy (SBRT) for the treatment of non-small cell lung cancer. FMs can also be used as a visualization aid during surgery with or without pleural dye marking. FMs allow the operator to confirm correct positioning on the target center and to facilitate accuracy of high-dose radiation treatments to small targets and targets in close proximity organs. FMs are placed percutaneously with image guidance or through video bronchoscope. Accurate placement of FMs or pleural dye marking is confirmed by follow-up imaging or during surgical resection (Folch, 2022). ENB may be used as an alternative method of FM placement that may result in fewer complications (Bowling, 2019).

Bowling and associates (2019) reviewed the safety and accuracy outcomes of ENB-guided FM placement in the participants of the NAVIGATE trial who underwent FM placement with the superDimension™ navigation system. The NAVIGATE trial, a prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system, included 258 adults who underwent elective FM placement. Concurrent procedures included FM placement and lung biopsy, FM placement and dye marking, FM placement alone and FM placement and dye marking and biopsy. The median overall procedure time was 57 minutes and 31 minutes for the ENB procedure; general anesthesia was used in 68.2% (176/258) of the cases. An average of 2.2 ± 1.7 FMs were placed in each session. A placement accuracy of 99.2% was based on subjective operator assessment, which authors admit may not be the most clinically appropriate indicator for SBRT success. When confirmed during follow-up imaging, 94.1% of the markers remained in place. Complication rates were reported as procedure-related pneumothorax rate 5.4% (14/258) overall, grade 2 or higher pneumothorax rate 3.1% (8/258) and respiratory failure rate 1.6% (4/258).

Using data from the NAVIGATE trial, Bowling and colleagues (2019a) reported on the 1-month interim analysis of 23 individuals who underwent pleural dye marking prior to lung resection. The objective of the study was to evaluate usage patterns, techniques and performance. Dye marking was conducted alone or concurrently with lesion or lymph node biopsy and/or FM placement. Fluoroscopy was used in all cases, EBUS was used in 4/23 cases. Following dye marking, surgical resection was attempted in all cases and the surgeon considered pleural dye marking adequate in 21/23 cases (91.3%).

Yanagiya and associates (2020) performed a meta-analysis evaluating the safety and efficacy of preoperative bronchoscopic marking. The authors used pooled data from several methods as well as subgroup analyses on individual methods. The most common method evaluated, dye marking under ENB, was used in 15 of the 25 total studies included in the review. The subgroup analyses calculated in a successful marking rate for ENB of 0.94 (95% CI, 0.91-0.96), but reported significant heterogeneity. The successful resection rate for ENB was 0.99 (95% CI, 0.97-1.00). These results were similar to the pooled rates (0.97; 95% CI, 0.95-0.99 and 0.98; 95% CI, 0.96-1.00, respectively). Bronchoscopic marking in general and ENB in particular appeared to be effective and safe.

Summary

One of the benefits of navigational bronchoscopy is the ability to biopsy and place fiducial markers or dye markers in the same procedure (Folch, 2022). Navigational bronchoscopy also allows for the biopsy of multiple nodules and mediastinal staging within the same procedure (Folch, 2022). While the lack of  real-time image guidance and the presence of CT-to-body divergence does limit the diagnostic yields compared to other techniques, such as TTNA, navigational bronchoscopy does provide an alternative method of obtaining samples in individuals when other options are not available (Folch, 2022). In individuals for whom nonsurgical biopsy is indicated when both transthoracic needle biopsy and conventional bronchoscopy are considered inadequate to accomplish the diagnostic or interventional objective, use of the device is likely to provide additional diagnostic information. In an attempt to address the shortcomings of navigational bronchoscopy and augment clinical utility, versions of navigational bronchoscopy combined with other technologies have been developed. ENB continues to be the most common form of navigational bronchoscopy utilized.

Bronchoscopy: An endoscopic test that utilizes either a rigid or a flexible catheter, in order to visualize and collect samples (washing, brushing, biopsy, culture, etc.) from the endobronchial tubes/branches of the respiratory system.

Diagnostic yield: A subset of the overall yield of tissue obtained during bronchoscopy which results a positive or negative diagnosis.

Navigational systems: Systems include a pre-operative imaging/planning component, which maps the intended course to the lesion. During the bronchoscopy, sensors attached to the bronchoscope allow for tracking of the catheter along the intended pathway. Use of navigational systems are intended to be used to access peripheral lung nodules and improve diagnostic yield.

Robotic bronchoscopy: A navigational bronchoscopy platform which includes a robotic arm, allowing the physician to interact with the bronchoscope through a controller arm. This direct interaction is thought to allow for more precise control by the operator.

Peer Reviewed Publications:

1. Aboudara M, Roller L, Rickman O, et al. Improved diagnostic yield for lung nodules with digital tomosynthesis-corrected navigational bronchoscopy: Initial experience with a novel adjunct. Respirology. 2020; 25(2):206-213.
2. Atkins NK, Marjara J, Kaifi JT, et al. Role of Computed tomography-guided biopsies in the era of electromagnetic navigational bronchoscopy: a retrospective study of factors predicting diagnostic yield in electromagnetic navigational bronchoscopy and computed tomography biopsies. J Clin Imaging Sci. 2020; 10:33.
3. Avasarala SK, Roller L, Katsis J, et al. Sight unseen: Diagnostic yield and safety outcomes of a novel multimodality navigation bronchoscopy platform with real-time target acquisition. Respiration. 2022;101(2):166-173.
4. Bessich JL, Sterman DH. Improving electromagnetic navigation: One nodule at a time. Respirology. 2020; 25(2):130-131.
5. Bhatt KM, Tandon YK, Graham R, et al. Electromagnetic navigational bronchoscopy versus CT-guided percutaneous sampling of peripheral indeterminate pulmonary nodules: a cohort study. Radiology. 2018; 286(3):1052-1061.
6. Bolton WD, Richey J, Ben-Or S, et al. Electromagnetic navigational bronchoscopy: a safe and effective method for fiducial marker placement in lung cancer patients. Am Surg. 2015; 81(7):659-662.
7. Bolton WD, Cochran T, Ben-Or S, et al. Electromagnetic navigational bronchoscopy reduces the time required for localization and resection of lung nodules. Innovations (Phila). 2017; 12(5):333-337.
8. Bowling MR, Folch EE, Khandhar SJ, et al. Fiducial marker placement with electromagnetic navigation bronchoscopy: a subgroup analysis of the prospective, multicenter NAVIGATE study. Ther Adv Respir Dis. 2019; 13:1753466619841234.
9. Bowling MR, Folch EE, Khandhar SJ, et al. Pleural dye marking of lung nodules by electromagnetic navigation bronchoscopy. Clin Respir J. 2019(a); 13(11):700-707.
10. Brownback KR, Quijano F, Latham HE, Simpson SQ. Electromagnetic navigational bronchoscopy in the diagnosis of lung lesions. J Bronchology Interv Pulmonol. 2012; 19(2):91-97.
11. Chaddha U, Kovacs SP, Manley C, et al. Robot-assisted bronchoscopy for pulmonary lesion diagnosis: results from the initial multicenter experience. BMC Pulm Med. 2019; 19(1):243.
12. Chen A, Pastis N, Furukawa B, Silvestri GA. The effect of respiratory motion on pulmonary nodule location during electromagnetic navigation bronchoscopy. Chest. 2015; 147(5):1275-1281.
13. Chen AC, Pastis NJ Jr, Mahajan AK, et al. Robotic bronchoscopy for peripheral pulmonary lesions: a multicenter pilot and feasibility study (BENEFIT). Chest. 2021; 159(2):845-852.
14. Chockalingam A, Hong K. Transthoracic needle aspiration: the past, present and future. J Thorac Dis. 2015; 7(Suppl 4):S292-S299.
15. Cicenia J, Avasarala SK, Gildea TR. Navigational bronchoscopy: a guide through history, current use, and developing technology. J Thorac Dis. 2020;1 2(6):3263-3271.
16. Cicenia J, Bhadra K, Sethi S, et al. Augmented fluoroscopy: a new and novel navigation platform for peripheral bronchoscopy. J Bronchology Interv Pulmonol. 2021; 28(2):116-123.
17. Eberhardt R, Anantham D, Ernst A, et al. Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med. 2007a; 176(1):36-41.
18. Eberhardt R, Anantham D, Herth F, et al. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest. 2007b; 131(6):1800-1805.
19. Eberhardt R, Morgan RK, Ernst A, et al. Comparison of suction catheter versus forceps biopsy for sampling of solitary pulmonary nodules guided by electromagnetic navigational bronchoscopy. Respiration. 2010; 79(1):54-60.
20. Fielding DIK, Bashirzadeh F, Son JH, et al. First human use of a new robotic-assisted fiber optic sensing navigation system for small peripheral pulmonary nodules. Respiration. 2019; 98(2):142-150.
21. Folch EE, Bowling MR, Pritchett MA, et al; NAVIGATE Study Investigators. NAVIGATE 24-Month Results: Electromagnetic Navigation Bronchoscopy for Pulmonary Lesions at 37 Centers in Europe and the United States. J Thorac Oncol. 2022; 17(4):519-531.
22. Folch EE, Labarca G, Ospina-Delgado D, et al. Sensitivity and Safety of Electromagnetic Navigation Bronchoscopy for Lung Cancer Diagnosis: Systematic Review and Meta-analysis. Chest. 2020; 158(4):1753-1769.
23. Folch EE, Pritchett MA, Nead MA, et al.; NAVIGATE Study Investigators. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: one-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019; 14(3):445-458.
24. Gex G, Pralong JA, Combescure C, et al. Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis. Respiration. 2014;87(2):165-176.
25. Gildea TR, Mazzone PJ, Karnak D, et al. Electromagnetic navigation diagnostic bronchoscopy: a prospective study. The Cleveland Clinic Foundation, Cleveland, OH. Am J Respir Crit Care Med. 2006; 174(9):982-989.
26. Hong H, Hahn S, Matsuguma H, et al. Pleural recurrence after transthoracic needle lung biopsy in stage I lung cancer: a systematic review and individual patient-level meta-analysis. Thorax. 2021; 76(6):582-590.
27. Jensen KW, Hsia DW, Seijo LM, et al. Multicenter experience with electromagnetic navigation bronchoscopy for the diagnosis of pulmonary nodules. J Bronchology Interv Pulmonol. 2012; 19(3):195-199.
28. Kent AJ, Byrnes KA, Chang SH. State of the art: robotic bronchoscopy. Semin Thorac Cardiovasc Surg. 2020; 32(4):1030-1035.
29. Khandhar SJ, Bowling MR, Flandes J, et al.; NAVIGATE Study Investigators. Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study. BMC Pulm Med. 2017; 17(1):59.
30. Krimsky WS, Minnich DJ, Cattaneo SM, et al. Thoracoscopic detection of occult indeterminate pulmonary nodules using bronchoscopic pleural dye marking. J Community Hosp Intern Med Perspect. 2014; 4.
31. Kupelian PA, Forbes A, Willoughby TR, et al. Implantation and stability of metallic fiducials within pulmonary lesions. Int J Radiation Oncol Biol Phys. 2007; 69(3):777-785.
32. Lamprecht B, Porsch P, Pirich C, Studnicka M. Electromagnetic navigation bronchoscopy in combination with PET-CT and rapid on-site cytopathologic examination for diagnosis of peripheral lung lesions. Lung. 2009; 187(1):55-59.
33. Lamprecht B, Porsch P, Wegleitner B, et al. Electromagnetic navigation bronchoscopy (ENB): increasing diagnostic yield. Respir Med. 2012; 106(5):710-715.
34. Loo FL, Halligan AM, Port JL, Hoda RS. The emerging technique of electromagnetic navigation bronchoscopy-guided fine-needle aspiration of peripheral lung lesions: promising results in 50 lesions. Cancer Cytopathol. 2014; 122(3):191-199.
35. McGuire AL, Myers R, Grant K, et al. The diagnostic accuracy and sensitivity for malignancy of radial-endobronchial ultrasound and electromagnetic navigation bronchoscopy for sampling of peripheral pulmonary lesions: Systematic review and meta-analysis. J Bronchology Interv Pulmonol. 2020; 27(2):106-121.
36. McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med. 2013; 369(10):910-919.
37. Nabavizadeh N, Zhang J, Elliott DA, et al. Electromagnetic navigational bronchoscopy-guided fiducial markers for lung stereotactic body radiation therapy: analysis of safety, feasibility, and interfraction stability. J Bronchology Interv Pulmonol. 2014; 21(2):123-130.
38. Odronic SI, Gildea TR, Chute DJ. Electromagnetic navigation bronchoscopy-guided fine needle aspiration for the diagnosis of lung lesions. Diagn Cytopathol. 2014; 42(12):1045-1050.
39. Oh JH, Choi CM, Kim S, et al. Diagnostic yield and safety of biopsy guided by electromagnetic navigation bronchoscopy for high-risk pulmonary nodules. Thorac Cancer. 2021; 12(10):1503-1510.
40. Ost DE, Ernst A, Lei X, et al.; AQuIRE Bronchoscopy Registry. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions: results of the AQuIRE Registry. Am J Respir Crit Care Med. 2016; 193(1):68-77.
41. Ozgul G, Cetinkaya E, Ozgul MA, et al. Efficacy and safety of electromagnetic navigation bronchoscopy with or without radial endobronchial ultrasound for peripheral lung lesions. Endosc Ultrasound. 2016; 5(3):189-195.
42. Pearlstein DP, Quinn CC, Burtis CC, et al. Electromagnetic navigation bronchoscopy performed by thoracic surgeons: one center's early success. Ann Thorac Surg. 2012; 93(3):944-949; discussion 949-950.
43. Pertzov B, Gershman E, Izhakian S, et al. The LungVision navigational platform for peripheral lung nodule biopsy and the added value of cryobiopsy. Thorac Cancer. 2021; 12(13):2007-2012.
44. Podder S, Chaudry S, Singh H, et al. Efficacy and Safety of Cone-Beam CT Augmented Electromagnetic Navigation Guided Bronchoscopic Biopsies of Indeterminate Pulmonary Nodules. Tomography. 2022; 8(4):2049-2058.
45. Pritchett MA, Schampaert S, de Groot JAH, et al. Cone-Beam CT With augmented fluoroscopy combined with electromagnetic navigation bronchoscopy for biopsy of pulmonary nodules. J Bronchology Interv Pulmonol. 2018; 25(4):274-282.
46. Rojas-Solano JR, Ugalde-Gamboa L, Machuzak M. Robotic bronchoscopy for diagnosis of suspected lung cancer: a feasibility study. J Bronchology Interv Pulmonol. 2018; 25(3):168-175.
47. Schroeder C, Hejal R, Linden PA. Coil spring fiducial markers placed safely using navigation bronchoscopy in inoperable patients allows accurate delivery of CyberKnife stereotactic radiosurgery. J Thorac Cardiovasc Surg. 2010; 140(5):1137-1142.
48. Schwarz Y, Greif J, Becker HD, et al. Real-time electromagnetic navigation bronchoscopy to peripheral lung lesions using overlaid CT images: the first human study. Chest. 2006; 129(4):988–994.
49. Seijo LM. Electromagnetic navigation bronchoscopy: clinical utility in the diagnosis of lung cancer. Lung Cancer (Auckl). 2016; 7:111-118.
50. Seijo LM, de Torres JP, Lozano MD, et al. Diagnostic yield of electromagnetic navigation bronchoscopy is highly dependent on the presence of a bronchus sign on CT imaging. Chest. 2010; 138(6):1316-1321.
51. Shulman L, Ost D. Advances in bronchoscopic diagnosis of lung cancer. Curr Opin Pulm Med. 2007; 13(4):271-277.
52. Silvestri GA, Bevill BT, Huang J, et al. An evaluation of diagnostic yield from bronchoscopy: The impact of clinical/radiographic factors, procedure type, and degree of suspicion for cancer. Chest. 2020; 157(6):1656-1664.
53. Simoff MJ, Pritchett MA, Reisenauer JS, et al. Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System. BMC Pulm Med. 2021; 21(1):322.
54. Stone E, Leong TL. Contemporary Concise Review 2021: Pulmonary nodules from detection to intervention. Respirology. 2022; 27(9):776-785.
55. Thiboutot J, Yarmus LB, Lee HJ, et al. Real-world application of the NAVIGATE trial. J Thorac Oncol. 2019; 14(7):e146-e147.
56. Tremblay A. Real-time electromagnetic navigation bronchoscopy for peripheral lesions: what about the negative predictive value? Chest. 2007; 131(1):328-329.
57. Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012; 142(2):385-393.
58. Weiser TS, Hyman K, Yun J, et al. Electromagnetic navigational bronchoscopy: a surgeon’s perspective. Ann Thorac Surg. 2008; 85(2):S797-S801.
59. Wilson DS, Bartlett RJ. Improved diagnostic yield of bronchoscopy in a community practice: combination of electromagnetic navigation system and rapid on-site evaluation. J Bronchol. 2007; 14(4):227-232.
60. Yarmus L, Akulian J, Wahidi Met l; Interventional Pulmonary Outcomes Group (IPOG). A prospective randomized comparative study of three guided bronchoscopic approaches for investigating pulmonary nodules: The PRECISION-1 Study. Chest. 2020; 157(3):694-701.
61. Yanagiya M, Kawahara T, Ueda K, et al. A meta-analysis of preoperative bronchoscopic marking for pulmonary nodules. Eur J Cardiothorac Surg. 2020; 58(1):40-50.
62. Zhang W, Chen S, Dong X, Lei P. Meta-analysis of the diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules. J Thorac Dis. 2015; 7(5):799-809.
63. Zheng X, Cao L, Zhang Y, et al. A novel electromagnetic navigation bronchoscopy system for the diagnosis of peripheral pulmonary nodules: a randomized clinical trial. Ann Am Thorac Soc. 2022; 19(10):1730-1739.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Callister ME, Baldwin DR, Akram AR, et al; British Thoracic Society Pulmonary Nodule Guideline Development Group; British Thoracic Society Standards of Care Committee. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax. 2015 Aug;70 Suppl 2:ii1-ii54.
2. Lewis SZ, Diekemper R, Addrizzo-Harris DJ. Methodology for development of guidelines for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):41S-50S.
3. National Clinical Practice Guidelines in Oncology^®. ^©2023 National Comprehensive Cancer Network, Inc. For additional information, visit the NCCN website:  http://www.nccn.org/index.asp. Accessed on August 31, 2023.
   • Lung Cancer Screening. V1.2024. July 19, 2023.
   • Non-Small Cell Lung Cancer. V3.2023. April 13, 2023.
4. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):e142S-165S.
5. Slatore CG, Horeweg N, Jett JR, et al; ATS Ad Hoc Committee on Setting a Research Framework for Pulmonary Nodule Evaluation. An official american thoracic society research statement: A research framework for pulmonary nodule evaluation and management. Am J Respir Crit Care Med. 2015; 192(4):500-514.
6. U.S. Food and Drug Administration. Center for Devices and Radiological Health (CDRH) 510(k) Premarket Notification Database.
   • Ig4^™ EndoBronchial. Summary of Safety and Effectiveness. No. K091934. Rockville, MD: FDA. December 2, 2009. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf9/K091934.pdf. Accessed on August 31, 2023.
   • ILLUMISITE Platform. Summary of Safety and Effectiveness. No. K191394. Rockville, MD: FDA. August 7, 2019. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf19/K191394.pdf. Accessed on August 31, 2023.
   • Ion Endoluminal System. Summary of Safety and Effectiveness. No. K202370. Rockville, MD: FDA. August 7, 2019. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf20/K202370.pdf. Accessed on August 31, 2023.
   • LungVision^™ Tool. Summary of Safety and Effectiveness. No. K172955. Rockville, MD: FDA. April 26, 2018. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf17/K172955.pdf. Accessed on August 31, 2023.
   • Monarch Endoscopy Platform. Summary of Safety and Effectiveness. No. K173760. Rockville, MD: FDA. March 22, 2018. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf17/K173760.pdf. Accessed on August 31, 2023.
   • superDimension^®/Bronchus inReach^TM System. Summary of Safety and Effectiveness. No. K081379. Rockville, MD: FDA. September 4, 2009. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf9/k092365.pdf . Accessed on August 31, 2023.
   • superDimension^® i-Logic^™ inReach^® System with the Edge^™ Catheter System. Summary of Safety and Effectiveness. No. K102604. Rockville, MD: FDA. October 7, 2010. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf10/K102604.pdf. Accessed on August 31, 2023.

1. American Cancer Society (ACS).
   • Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer.html. Accessed on August 31, 2023.
   • Key Statistics for Lung Cancer. Available at: https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed on August 31, 2023.
2. American Lung Association. Lung Cancer Diagnosis. Available at:  http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/lung-cancer/diagnosing-and-treating/how-lung-cancer-diagnosed.html. Accessed on August 30, 2023.
3. MedlinePlus. Bronchoscopy.  Available at: https://medlineplus.gov/ency/article/003857.htm. Accessed on August 31, 2023.

Electromagnetic Navigational Bronchoscopy (ENB)
ig4 EndoBronchial System
iLogic Electromagnetic Navigation Bronchoscopy
ILLUMISITE™ (Medtronic, Minneapolis, MN) 
Ion Endoluminal System
LungPoint Virtual Bronchoscopic Navigation
Monarch Platform
SpiN Drive System
superDimension/Bronchus inReach System

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.