Electromagnetic Navigation Bronchoscopy - CAM 701122

Description:
Electromagnetic navigation bronchoscopy (ENB) is intended to enhance standard bronchoscopy by providing a 3-dimensional roadmap of the lungs and real-time information about the position of the steerable probe during bronchoscopy. The purpose of ENB is to allow navigation to distal regions of the lungs, so that suspicious lesions can be biopsied and to allow fiducial markers placement.

For individuals who have suspicious peripheral pulmonary lesion(s) when flexible bronchoscopy alone or with endobronchial ultrasound are inadequate to sample the pulmonary lesion(s), the evidence includes meta-analyses, a randomized controlled trial, and uncontrolled observational studies. A 2015 meta-analysis of 17 studies of ENB reported a large pooled positive likelihood ratio but a small negative likelihood ratio (0.22; 95% CI 0.15 to 0.32). Similarly, a 2014 meta-analysis of 15 studies found that navigation success was high, but diagnostic yield (64.9; 95% CI 59.2 to 70.3) and negative predictive value (52.1; 95% CI 43.5 to 60.6) were relatively low. Both systematic reviews assessed the methodological quality of the evidence as low. Results from 2 large prospective multicenter uncontrolled studies, AQuiRE and NAVIGATE, provide information about test characteristics and safety of ENB. An analysis of more than 500 patients included in the AQuiRE registry found a diagnostic yield of ENB that was lower than in other studies, and lower than bronchoscopy without ENB or EBUS. In the US cohort of the NAVIGATE study, the 12-month diagnostic yield was 72.9%. Overall, 4.3% of patients experienced pneumothorax, and pneumothorax requiring hospitalization or intervention occurred in 35 of 1,215 patients (2.9%). Bronchopulmonary hemorrhage overall occurred in 2.5% of patients overall and CTAE grade 2 or higher in 1.5%. There were no deaths related to the ENB device. Limitations of the published evidence preclude determining the effects of the technology on net health outcome. Evidence reported through clinical input supports that this use provides a clinically meaningful improvement in net health outcome and is consistent with generally accepted medical practice. ENB is generally reserved for the most difficult patients, who are poor or borderline candidates for surgery and transthoracic sampling. In this context, the "low yield" observed in observational studies was actually high for this highly selected population. ENB, when used as an option in the armamentarium of the bronchoscopist, is a highly useful and low risk modality for proper diagnosis and staging of lung cancer. For example, patients who are able to achieve a positive biopsy result through ENB benefit by getting a diagnostic result to appropriately guide treatment while avoiding transthoracic needle biopsy which has a 2-4 times higher risk of pneumothorax than a bronchoscopic biopsy approach. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have enlarged MLNs who receive ENB with flexible bronchoscopy, the evidence includes an RCT and observational studies. Relevant outcomes are test accuracy and validity, other test performance measures, and treatment-related morbidity. There is less published literature on ENB for diagnosing MLN than for diagnosing pulmonary lesions. One RCT identified found higher sampling and diagnostic success with ENB-guided transbronchial needle aspiration (TBNA) than with conventional TBNA. EBUS, which has been shown to be superior to conventional TBNA, was not used as the comparator. The RCT did not report the diagnostic accuracy of ENB for identifying malignancy, and this was also not reported in uncontrolled studies. Limitations of the published evidence preclude determining the effects of the technology on net health outcome. Evidence reported through clinical input is not generally supportive of a clinically meaningful improvement in net health outcome. MLN diagnosis was an early indication for ENB which has been largely replaced by EBUS. One could consider it in the uncommon scenario in which linear EBUS is not available and the patient is already having a ENB procedure for a peripheral nodule. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have lung tumor(s) who need fiducial marker placement prior to treatment when flexible bronchoscopy alone or with endobronchial ultrasound are inadequate to place the markers near the pulmonary lesion(s), the evidence includes one comparative observational study and several case series. The relevant outcomes are health status measures and treatment-related morbidity. In the largest series, a subgroup analysis of 258 patients from the NAVIGATE study, the subjective assessment of outcome was that 99.2% of markers were accurately placed and 94.1% were retained at follow-up (mean 8.1 days postprocedure). Pneumothorax of any grade occurred in 5.4% of patients, and grade 2 or higher pneumothorax occurred in 3.1%. Limitations of the published evidence preclude determining the effects of the technology on net health outcome. Evidence reported through clinical input supports that this use provides a clinically meaningful improvement in net health outcome and is consistent with generally accepted medical practice. The key advantage to ENB placement is the markedly reduced risk of pneumothorax compared to the transthoracic approach. Patients being treated with targeted radiation are typically those with advanced respiratory disease who cannot undergo surgical resection. They are also more at risk for pneumothorax and resultant further complications. As the markers need to be near and not necessarily in a lesion, the accuracy advantage of a transthoracic approach is outweighed by the safety advantage of ENB over a transthoracic approach. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

Background 
PULMONARY NODULES
Pulmonary nodules are identified on plain chest radiographs, or chest computed tomography scans. Although most nodules are benign, some are cancerous, and early diagnosis of lung cancer is desirable because of the poor prognosis when it is diagnosed later.

Diagnosis
The method used to diagnose lung cancer depends on a number of factors, including lesion size, shape, location, as well as the clinical history and status of the patient. Peripheral lung lesions and solitary pulmonary nodules (most often defined as asymptomatic nodules <6 mm) are more difficult to evaluate than larger, centrally located lesions. There are several options for diagnosing malignant disease, but none of the methods is ideal. Sputum cytology is the least invasive approach. Reported sensitivity rates are relatively low and vary widely across studies; sensitivity is lower for peripheral lesions. Sputum cytology, however, has a high specificity; and a positive test may obviate the need for more invasive testing. Flexible bronchoscopy, a minimally invasive procedure, is an established approach to evaluate pulmonary nodules. The sensitivity of flexible bronchoscopy for diagnosing bronchogenic carcinoma has been estimated at 88% for central lesions and 78% for peripheral lesions. For small peripheral lesions (<1.5 cm in diameter), the sensitivity may be as low as 10%. The diagnostic accuracy of transthoracic needle aspiration for solitary pulmonary nodules tends to be higher than that of bronchoscopy; the sensitivity and specificity are both approximately 94%. A disadvantage of transthoracic needle aspiration is that a pneumothorax develops in 11% to 25% of patients, and 5% to 14% require insertion of a chest tube. Positron emission tomography scans are also highly sensitive for evaluating pulmonary nodules yet may miss lesions less than 1 cm in size. A lung biopsy is the criterion standard for diagnosing pulmonary nodules but is an invasive procedure.1,2,3

Advances in technology may increase the yield of established diagnostic methods. Computed tomography scanning equipment can be used to guide bronchoscopy and bronchoscopic transbronchial needle biopsy but have the disadvantage of exposing the patient and staff to radiation. Endobronchial ultrasound by radial probes, previously used in the perioperative staging of lung cancer, can also be used to locate and guide sampling of peripheral lesions. Endobronchial ultrasound is reported to increase the diagnostic yield of flexible bronchoscopy to at least 82%, regardless of lesion size or location.1

Marker Placement
Another proposed enhancement to standard bronchoscopy is electromagnetic navigation bronchoscopy. Electromagnetic navigation bronchoscopy enhances standard bronchoscopy by providing a 3- dimensional roadmap of the lungs and real-time information about the position of the steerable probe during bronchoscopy. The purpose of electromagnetic navigation bronchoscopy is to allow navigation to distal regions of the lungs. Once the navigation catheter is in place, any endoscopic tool can be inserted through the channel in the catheter to the target. This includes insertion of transbronchial forceps to biopsy the lesion. Also, the guide catheter can be used to place fiducial markers. Markers are loaded in the proximal end of the catheter with a guide wire inserted through the catheter.

Regulatory Status
In 2004, the superDimension/Bronchus™ inReach™ system (superDimension) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The system includes planning and navigation software, a disposable extended working channel, and a disposable steerable guide. The FDA-cleared indication is for displaying images of the tracheobronchial tree that aids physicians in guiding endoscopic tools in the pulmonary tract. The device is not intended as an endoscopic tool; it does not make a diagnosis; and it is not approved for pediatric use. As of June 2016, the current version of the product is the Medtronic SuperDimension Navigation System (Medtronic).

In December 2009, the ig4™ EndoBronchial system (Veran Medical) was cleared for marketing by FDA through the 510(k) process. The system was considered to be substantially equivalent to the InReach system and is marketed as the SPiN™ Drive system.

In April 2018, LungVision (Body Vision Medical) was cleared for marketing by the FDA through the 510(k) process (K172955). ). The FDA determined that this device was substantially equivalent to existing devices for use "segment previously acquired 3D CT [computed tomography] datasets and overlay and register these 3D segmented data sets with fluoroscopic live X-ray images of the same anatomy in order to support catheter/device navigation during pulmonary procedure". FDA product code: EOQ.

Several additional navigation software-only systems have been cleared for marketing by FDA through the 510(k) process. These include:

  • December 2008: The LungPoint® virtual bronchoscopic navigation (VPN) system (Broncus Technologies, Mountain View, CA).
  • June 2010: The bf-NAVI VPN system (Emergo Group, Austin, TX)

FDA product codes: JAK, LLZ. 

Two ENB systems are currently available, the SPiN Thoracic Navigation System™ (Veran Medical Technologies) and the superDimension™ navigation system. (medtronic) 

Related Policies
20310 Real-Time Intra-Fraction Motion Management During Radiation Therapy
60110 Stereotactic Radiosurgery and Stereotactic Body Radiotherapy
60130 Screening for Lung Cancer Using Computed Tomography Scanning
60158 Endobronchial Ultrasound for Diagnosis and Staging of Lung Cancer

Policy:
When flexible bronchoscopy alone, or with endobronchial ultrasound, are considered inadequate to accomplish the diagnostic or interventional objective, electromagnetic navigation bronchoscopy (ENB) may be considered MEDICALLY NECESSARY to:

  • establish a diagnosis of suspicious peripheral pulmonary lesion(s) or
  • place fiducial markers within lung tumor(s) prior to treatment

Electromagnetic navigation bronchoscopy is investigational/unproven therefore considered NOT MEDICALLY NECESSARY for use with flexible bronchoscopy for the diagnosis of mediastinal lymph nodes as well as all other uses not covered above.

Policy Guidelines
Bronchoscopists performing ENB requires specific training in the procedure.

Enlarged Mediastinal Nodes was an early indication for ENB which has been largely replaced by EBUS. One could consider it in the uncommon scenario in which linear EBUS is not available and the patient is having an ENB procedure for a peripheral nodule in any case.

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices, drugs, or biologics approved by the U.S. Food and Drug Administration may not be considered investigational, and thus these devices may be assessed only on the basis of their medical necessity.

Rationale 
Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Electromagnetic Navigation Bronchoscopy to Aid Diagnosing Pulmonary Lesions
Clinical Context and Test Purpose
The purpose of using ENB with flexible bronchoscopy in patients who have suspicious peripheral pulmonary lesions is to confirm a diagnosis of lung cancer and to initiate treatment.

The question addressed in this evidence review is: Does the use of ENB with flexible bronchoscopy improve health outcomes in individuals with suspicious peripheral pulmonary lesions?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with suspicious peripheral pulmonary lesions.

Interventions
The test being considered is ENB with flexible bronchoscopy.

Comparators
The following tests are currently being used: flexible bronchoscopy only, computed tomography (CT)-guided needle biopsy and endobronchial ultrasound with flexible bronchoscopy.

Outcomes
The general outcomes of interest are the accurate identification of cancerous lesions and a reduction in disease-related morbidity and mortality. Potentially harmful outcomes are those resulting from false-positive or false-negative test results. False-positive test results can lead to unnecessary treatment. False-negative test results can lead to failure to initiate therapy. Potential procedure-related adverse events include pneumothorax, bronchopulmonary hemorrhage, and respiratory complications.

The time frame for evaluating the performance of the test varies the time from the initial CT scan to an invasive diagnostic procedure to up to 2 years, which would be the typical follow-up needed for some lung nodules.

Study Selection Criteria
For the evaluation of clinical validity of the ENB with flexible bronchoscopy, studies that meet the following eligibility criteria were considered:

  • Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
  • Included a suitable reference standard
  • Patient/sample clinical characteristics were described
  • Patient/sample selection criteria were described.

Several studies were excluded from the evaluation of the clinical validity of the because they did not use the marketed version of the test, did not include information needed to calculate performance characteristics, did not adequately describe the patient characteristics, or did not adequately describe patient selection criteria.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Systematic Reviews
Folch et al. (2020) published a systematic review of the literature on the sensitivity and safety of ENB for diagnosing peripheral pulmonary lesions suspected of cancer.4, Forty prospective and retrospective studies (N=3,342 patients) were included in the analysis. Many of the included studies were single-center, single arm, and retrospective. Because most studies did not use a proper reference standard, the authors reported that most studies had a higher or unclear risk of bias regarding patient selection, index test, and the reference standard. Most studies used the superDimension system.

A systematic review of the literature on the diagnostic yield and safety of ENB was published by Zhang et al. (2015).5 Reviewers updated a systematic review by Gex et al. (2014)6, with newer studies. The Zhang et al. (2015) review included prospective and retrospective studies of patients with peripheral nodules confirmed by a radiographic evaluation that had more than 10 patients and reported the diagnostic yield of ENB for peripheral lung nodules or lesions. Seventeen studies with 1161 lung nodules or lesions in 1,106 patients met the eligibility criteria. Reviewers used the Quality Assessment of Diagnostic Accuracy Studies tool to evaluate the methodologic quality of selected studies, and overall quality was poor. None compared ENB with surgery, and, in almost all studies, reviewers reported it was uncertain whether the selected patients were representative of the population that would undergo ENB in an actual clinical setting.

Results of pooled analyses are reported in Table 1. True-positive findings are those in which ENB biopsy yielded a definitive malignant diagnosis. True-negatives were defined as benign findings on ENB biopsy, confirmed by follow-up procedures. The Gex et al. (2014) systematic review, which included 15 studies (N =971 patients), reported somewhat different outcomes (see Table 1).

Table 1. Meta-Analyses of Electromagnetic Navigation Bronchoscopy Performance

Outcomes Rate (95% Confidence Interval), % Rate (95% Confidence Interval), %  
  Folch et al. (2020)4 Zhang et al. (2015)5 Gex et al. (2014)6
Sensitivity for malignancy 77 (72 to 78) using random effects model; 76 (74 to 78) using fixed effect model 82 (79 to 85) 71.1 (64.6 to 76.8)
Specificity for malignancy 100 (99 to 100) 100 (98 to 100)  
Positive likelihood ratio 15.8 (10.3 to 24.2) 18.67 (9.04 to 38.55)  
Negative likelihood ratio 0.2 (0.1 to 0.3) 0.22 (0.15 to 0.32)  
Diagnostic odds ratio   97.36 (43.75 to 216.69)  
Navigation success     97.4 (95.4 to 98.5)
Diagnostic yield     64.9 (59.2 to 70.3)
Accuracy for malignancy     78.6 (72.8 to 83.4)
Negative predictive value     52.1 (43.5 to 60.6)
Negative predictive value of intermediate benign results     78.5 (53.1 to 92.1)

As reported by Gex et al. (2014), whereas the navigation success rate using ENB was generally very high, the diagnostic yield and negative predictive value (NPV) were relatively low.6 Moreover, in Folch et al. (2020) and Zhang et al. (2015), the positive likelihood ratio was large, but the negative likelihood ratio (0.2 and 0.22, respectively) suggested only a small decrease in the likelihood of disease following the test.4,5 Folch and Zhang did not conduct a pooled analysis of diagnostic yield. As stated at the beginning of this section, the evidence of particular interest is whether the test can correctly identify patients who do not have malignancy (i.e., high NPV or low negative likelihood ratio). Studies included in the meta-analyses were limited because the surgical biopsy was not used as the criterion standard; it is unclear whether follow-up was long enough to confirm ENB diagnoses.

The pneumothorax rate following ENB was 2% in Folch et al. (2020), 5.9% in Zhang et al. (2015), and 3.1% in Gex et al. (2014) (1.6% required chest tube placement for pneumothorax).5,6,4 Zhang et al. (2015) stated that 2 of the pneumothoraxes were induced by transbronchial biopsy and the others were unrelated to the ENB procedure. Folch et al. (2020) also reported a risk of major and minor bronchopulmonary bleeding of 0.8% and 1%, respectively, and risk of acute respiratory failure of 0.6%.4

Randomized Controlled Trials
Eberhardt et al. (2007) published the only randomized controlled trial (RCT) to evaluate ENB for the diagnosis of pulmonary nodules.7 This trial used surgical biopsy as a criterion standard confirmation of diagnosis. Patients were randomized to ENB only, endobronchial ultrasound only, or the combination of ENB and endobronchial ultrasound. Whereas ENB is designed to help navigate to the target but cannot visualize the lesion, endobronchial ultrasound is unable to guide navigation but enables direct visualization of the target lesion before the biopsy. The trial included 120 patients with evidence of peripheral lung lesions or solitary pulmonary nodules and who were candidates for elective bronchoscopy or surgery. In all 3 arms, only forceps biopsy specimens were taken, and fluoroscopy was not used to guide the biopsies. The primary outcome was the diagnostic yield, defined as the ability to yield a definitive diagnosis consistent with clinical presentation. If transbronchial lung biopsy did not provide a diagnosis, patients were referred for a surgical biopsy. The mean size of the lesions was 26 mm.

Two patients who did not receive a surgical biopsy were excluded from the final analysis. Of the remaining 118 patients, 85 (72%) had a diagnostic result via bronchoscopy, and 33 required a surgical biopsy. The diagnostic yield by intervention group was 59% (23/39) with ENB only, 69% (27/39) with endobronchial ultrasound only, and 88% (35/40) with ENB plus endobronchial ultrasound ; the yield was significantly higher in the combined group. The NPV for the malignant disease was 44% (10/23) with ENB only, 44% (7/16) with endobronchial ultrasound only, and 75% (9/12) with combined ENB and endobronchial ultrasound. Note that the number of cases was small, and thus the NPV is an imprecise estimate. Moreover, the trialists stated that the yield in the ENB only group was somewhat lower than in other studies; they attributed this to factors such as the use of forceps for biopsy (rather than forceps and endobronchial brushes, which would be considered standard) and/or an improved diagnosis using a criterion standard. The pneumothorax rate was 6%, which did not differ significantly across the 3 groups.

Uncontrolled Studies
One key uncontrolled prospective, multicenter observational study is the NAVIGATE study. NAVIGATE is a prospective, multicenter (n=37 sites) analysis of outcomes in patients who received ENB in U.S. and European centers. The study has broad inclusion criteria, including all adults who were candidates for ENB based on physician discretion, guideline recommendations, and institutional protocol. Participating physicians needed to have previous experience with ENB. Analyses of 1-month data on the first 1000 patients and 12-month data from the U.S. cohort have been published.8,9 Twelve-month follow-up of the European cohort and 2 year follow-up are ongoing.

Khandhar et al. (2017) published a preplanned 1-month interim analysis of first 1,000 patients from the NAVIGATE study.8 The analysis focused on safety outcomes; the primary endpoint was pneumothorax. Most of the first 1,000 patients (n=964 [96%]) had ENB for evaluation of lung lesions. Any grade pneumothorax occurred in 49 (4.9%) of 1000 patients and pneumothorax of grade 2 or higher occurred in 32 (3.2%) patients. The rate of bronchopulmonary hemorrhage was 2.3%. There were 23 deaths by the 1-month follow-up, none was considered related to the ENB device but 1 was deemed related to general anesthesia complications.

Folch et al. (2019) published 1 year results from the U.S. cohort of NAVIGATE (1,215 patients at 29 sites).9 This analysis included diagnostic outcomes as well as adverse events. Twelve-month follow-up was completed in 976 of 1215 (80.3%) patients. Navigation was successful and tissue was obtained in 1092 of the 1157 patients who received ENB for lung lesion biopsy (94.4%). Of these 1092 biopsies, 44.3% diagnosed malignancy (484) and 55.7% (608) were negative. As of 12 months, 284 initially negative outcomes were considered true-negative and 220 were false-negative. The 12-month diagnostic yield was 72.9% and ranged from 66.4% to 75.4% assuming all deferred cases were false-negatives and true-negatives, respectively.

Most adverse events occurred within the first-month post-procedure and were previously reported in Khandar et al. (2017). Overall, 4.3% of the patients had experienced pneumothorax. Pneumothorax requiring hospitalization or intervention (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher) occurred in 35 of 1215 patients (2.9%). Bronchopulmonary hemorrhage overall occurred in 2.5% of patients overall and CTCAE grade 2 or higher in 1.5%. Grade 4 or higher respiratory failure occurred in 0.7% of patients. There were 23 deaths at 12 months, none related to the ENB device. There was 1 anesthesia-related death 9 days post-procedure in a patient with multiple comorbidities.

Key uncontrolled observational studies not included in the meta-analyses are described next, focusing on prospective multicenter studies. The American College of Chest Physicians has established a registry of bronchoscopies performed for the diagnosis of peripheral lung nodules or masses to evaluate the diagnostic yield of different approaches in clinical practice, which may differ from findings in the clinical trial setting. Data from this registry, called AQuiRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education), were published by Ost et al. (2016).10, The primary outcome of this analysis was the diagnostic yield of bronchoscopy, defined as the ability to obtain a specific malignant or benign diagnosis. Bronchoscopy was diagnostic in 312 (53.7%) of 581 peripheral lesions. Diagnostic yield was 63.7% for bronchoscopy with no endobronchial ultrasound or ENB, 57.0% with endobronchial ultrasound alone, 38.5% with ENB alone, and 47.1% with ENB plus endobronchial ultrasound. ENB was reserved for the most difficult patients. They tended to be poor or borderline candidates for surgery and transthoracic sampling. The procedure was planned for ENB whether or not eventually used and ENB was done only when the other approaches were inadequate. In this context, the "low yield" observed for ENB was actually high for this highly selected population. Complications occurred in 13 (2.2%) of 591 patients. Pneumothorax occurred in 10 (1.7%) patients, 6 of who required chest tubes. Pneumothorax rates were not reported for bronchoscopy with and without ENB. In AQuiRE, ENB was reserved for the most difficult patients.

Two prospective observational studies have examined the sequential use of ENB; endobronchial ultrasound was used initially, with the addition of ENB when endobronchial ultrasound failed to reach or diagnose the lesion. A study by Chee et al. (2013) included 60 patients with peripheral pulmonary lesions.11 Patients either had a previous negative CT-guided biopsy or did not have 1 due to technical difficulties. An attempt was first made to identify the lesion using peripheral endobronchial ultrasound and, if not identified, then an ENB system was used. Nodules were identified by endobronchial ultrasound alone in 45 (75%) of 60 cases. ENB was used in 15 (25%) cases, and in 11 (73%) of these cases the lesion was identified. Peripheral endobronchial ultrasound led to a diagnosis in 26 cases and ENB in an additional 4 cases, for a total diagnostic yield of 30 (50%) of 60 cases. In this study, the extent of improved diagnosis with ENB over endobronchial ultrasound alone was not statistically significant (p=0.125). The rate of pneumothorax was 8% (5/60 patients); the addition of ENB did not alter the pneumothorax rate.

Clinically Useful
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs.

No RCTs were identified that evaluated health outcomes for the use of ENB.

Chain of Evidence
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.

Because the clinical validity of ENB cannot be established, a chain of evidence cannot be constructed.

Section Summary: Electromagnetic Navigation Bronchoscopy to Aid Diagnosing Pulmonary Lesions
A 2020 meta-analysis of 40 studies and a 2015 meta-analysis of 17 studies of ENB reported a large pooled positive likelihood ratio but a small negative likelihood ratio (0.2 to 0.22 ). Similarly, a 2014 meta-analysis of 15 studies found that navigation success was high, but diagnostic yield (64.9; 95% CI 59.2 to 70.3) and NPV (52.1; 95% CI 43.5 to 60.6) were relatively low. The systematic reviews assessed the methodological quality of the evidence as low. Results from 2 large prospective multicenter uncontrolled studies, AQuiRE and NAVIGATE, provide information about test characteristics and safety of ENB. An analysis of more than 500 patients included in the AQuiRE registry found a diagnostic yield of ENB that was lower than in other studies, and lower than bronchoscopy without ENB or endobronchial ultrasound. In the U.S. cohort of the NAVIGATE study, the 12-month diagnostic yield was 72.9%. Overall, 4.3% of patients experienced pneumothorax, and pneumothorax requiring hospitalization or intervention occurred in 35 of 1215 patients (2.9%). Bronchopulmonary hemorrhage overall occurred in 2.5% of patients overall and CTCAE grade 2 or higher in 1.5%. There were no deaths related to the ENB device.

Electromagnetic Navigation Bronchoscopy to Aid in the Diagnosis of Mediastinal Lymph Node(s)
Clinical Context and Test Purpose
The purpose of using ENB with flexible bronchoscopy in patients who have enlarged mediastinal lymph nodes is to inform a decision whether to initiate treatment for lung cancer.

The question addressed in this evidence review is: Does the use of ENB improve health outcomes in individuals with enlarged mediastinal lymph nodes?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with enlarged mediastinal lymph nodes

Interventions
The test being considered is ENB with flexible bronchoscopy.

Comparators
The following tests are currently being used: flexible bronchoscopy only, CT-guided needle biopsy, and endobronchial ultrasound with flexible bronchoscopy.

Outcomes
The general outcomes of interest are the accurate identification of mediastinal lymph nodes and reduction in disease-related morbidity and mortality. Potentially harmful outcomes are those resulting from false-positive or false-negative test results. False-positive test results can lead to unnecessary treatment. False-negative test results can lead to failure to initiate. Potential procedure-related adverse events include pneumothorax, bronchopulmonary hemorrhage, and respiratory complications. The time frame for outcomes measures varies from short-term development of invasive procedure-related complications to long-term procedure-related complications, disease diagnosis, or overall survival.

Study Selection Criteria
For the evaluation of clinical validity of the ENB with flexible bronchoscopy, studies that meet the following eligibility criteria were considered:

  • Reported on the accuracy of the marketed version of the technology (including any algorithms used to calculate scores)
  • Included a suitable reference standard
  • Patient/sample clinical characteristics were described
  • Patient/sample selection criteria were described.

Several studies were excluded from the evaluation of the clinical validity of the because they did not use the marketed version of the test, did not include information needed to calculate performance characteristics, did not adequately describe the patient characteristics, or did not adequately describe patient selection criteria.

Clinically Valid
A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence
Randomized Controlled Trials
One RCT was identified on ENB for the diagnosis of mediastinal lymph nodes The trial, reported by Diken et al. (2015), included 94 patients with mediastinal lymphadenopathy with a short axis greater than 1 cm on CT and/or increased uptake on positron emission tomography.12 Patients were randomized to conventional transbronchial needle aspiration (TBNA; n=50) or ENB-guided TBNA (n=44). All samples were evaluated by a blinded cytopathologist. Sampling success was defined as the presence of lymphoid tissue in the sample, and diagnostic success was the ability to make a diagnosis using the sample. Diagnoses were confirmed by 1 of several methods such as mediastinoscopy, thoracotomy, or radiologic follow-up. Final diagnoses were sarcoidosis (n=29), tuberculous lymphadenitis (n=12), non-small-cell lung cancer (n=20), small-cell lung cancer (n=12), benign lymph node (n=5), and others (n=5). Sampling success was 82.7% in the ENB group and 51.6% in the conventional TBNA group (p<0.001); diagnostic success was 72.8% in the ENB group and 42.2% in the conventional TBNA group (p<0.001). When samples were stratified by mediastinal lymph node size, both sampling success and diagnostic success were significantly higher with ENB than with conventional TBNA in mediastinal lymph nodes 15 mm or less and more than 15 mm. The trialists noted that, although endobronchial ultrasound -guided TBNA has been shown to have higher diagnostic yields than conventional TBNA, endobronchial ultrasound was not compared with ENB because it was not available at the institution in Turkey conducting the study. No pneumothorax or other major adverse events were reported for either group.

Uncontrolled Studies
No large uncontrolled studies were identified that focused on ENB for the diagnosing of mediastinal lymph nodes. A series by Wilson et al. (2007) included both patients with suspicious lung lesions and enlarged mediastinal lymph nodes.13 There was no consistent protocol for confirming the diagnosis, although the authors stated that most patients were followed for confirmation of diagnosis. ENB was used to locate, register, and navigate to the lesions. Once navigation was completed, fluoroscopic guidance was used to verify its accuracy and to aid in the biopsy or TBNA. Sixty-seven (94%) of 71 mediastinal lymph nodes were successfully reached, and tissue samples for biopsy were obtained from all of them. The primary study outcome was the diagnostic yield on the day of the procedure; this was obtained for 64 (96%) of 67 of the lymph nodes reached.

Clinically Useful
A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

Direct Evidence
Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from RCTs.

No RCTs were identified that evaluated health outcomes for the use of ENB.

Chain of Evidence
Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility.

Because the clinical validity of ENB cannot be established, a chain of evidence cannot be constructed.

Section Summary: Electromagnetic Navigation Bronchoscopy to Aid in the Diagnosis of Mediastinal Lymph Node (s)
There is less published literature on ENB for diagnosing mediastinal lymph nodes than for diagnosing pulmonary lesions. One RCT found higher sampling and diagnostic success with ENB-guided TBNA than with conventional TBNA. Endobronchial ultrasound , which has been shown to be superior to conventional TBNA, was not used as the comparator. The RCT did not report the diagnostic accuracy of ENB for identifying malignancy, and this was also not reported in uncontrolled studies.

Electromagnetic Navigation Bronchoscopy to Aid in Placement of Fiducial Markers Prior to Treatment
Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The RCT is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Clinical Context and Therapy Purpose
The purpose of using ENB with flexible bronchoscopy in patients who have lung tumors requiring placement of fiducial markers when flexible bronchoscopy alone or with endobronchial ultrasound are inadequate to place the markers near the pulmonary lesion(s) s to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of ENB improve health outcomes in individuals with lung tumors requiring placement of fiducial markers?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with lung tumors requiring placement of fiducial markers prior to treatment when flexible bronchoscopy alone or with endobronchial ultrasound is inadequate to place the markers near the pulmonary lesion(s).

Intervention
The intervention of interest is ENB with the placement of fiducial markers.

The purpose of electromagnetic navigation bronchoscopy is to allow navigation to distal regions of the lungs. Once the navigation catheter is in place, any endoscopic tool can be inserted through the channel in the catheter to the target. The guide catheter can be used to place fiducial markers. Markers are loaded in the proximal end of the catheter with a guidewire inserted through the catheter.

Comparators
The following practice is currently being used: placement of fiducial markers using CT or ultrasound guidance.

Outcomes
The general outcomes of interest are a reduction in surgical complications compared with other surgical techniques.

The time frame for outcomes measures varies from short-term development of invasive procedure-related complications to long-term procedure-related complications, disease progression, or overall survival.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

  • To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  • In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  • To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
  • Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Observational Studies and Case Series
Evaluation of ENB as an aid to the placement of fiducial markers involves searching for evidence that there are better clinical outcomes when ENB is used to place markers than when fiducials are placed using another method or when no fiducial markers are used. This review only evaluates the use of ENB to place fiducial markers; it does not evaluate the role of fiducial markers in radiotherapy.

Only one study was identified that compared fiducial marker placement using ENB with another method of fiducial marker placement; it was not randomized. This study, by Kupelian et al. (2007), included 28 patients scheduled for radiotherapy for early-stage lung cancer.14 Follow-up data were available for 23 (82%) patients; 15 had markers placed transcutaneously under CT or fluoroscopic guidance, and 8 patients had markers placed transbronchially with ENB. At least 1 marker was placed successfully within or near a lung tumor in all patients. The fiducial markers did not show substantial migration during treatment with either method of marker placement. The only clinical outcome reported was the rate of pneumothorax; 8 of 15 patients with transcutaneous placement developed a pneumothorax, 6 of whom required chest tubes. In contrast, none of the 8 patients with transbronchial placement developed pneumothorax. This study had a small sample size and a substantial dropout rate.

Several case series were identified.8,15,16,17,18,19,20 Studies with the largest sample sizes are described next.

Two publications from the ongoing NAVIGATE observational cohort study (described above) have reported preliminary outcomes in patients who had fiducial marker placement with ENB.8,21 In an interim analysis reported by Khandhar et al. (2017), 210 patients received 417 fiducial markers.8 The subjective operator assessment of accurate placement of the fiducial markers was 208 (99%) in the 210 patients and 192 (94%) of 205 fiducial markers were retained at follow-up imaging. The timing of follow-up imaging was not specified. ENB-related adverse events included 8 (4%) cases of pneumothorax (grade ≥2), 3 cases of respiratory failure (grade ≥4), and a single bronchopulmonary hemorrhage (grade 1). Bowling et al. (2019) reported 1 month outcomes in 258 patients who had a total of 563 fiducial markers placed at 21 centers in the U.S.21 Follow-up data were available for 255/258 patients (99.8%). Based on subjective operator assessment, fiducial markers were accurately placed in 99.2% of patients (256/258). Follow-up imaging occurred an average of 8.1 days postprocedure and showed that 239 of 254 markers remained in place (239/254). Fourteen patients (5.4%) experienced pneumothorax; in 8 patients (3.1%) the pneumothorax was rated CTCAE grade 2 or higher.

Bolton et al. (2015) retrospectively reported on ENB fiducial marker placement in 64 patients (68 lung lesions) for guiding stereotactic radiotherapy.17 A total of 190 fiducial markers were placed, 133 in upper-lobe lesions and 57 markers in lower-lobe lesions. The rate of marker retention (the study's primary endpoint) was 156 (82%) of 190. Retention rate, by lobe, ranged from 68 (80%) of 85 in the right upper lobe to 10 (100%) of 10 in the right middle lobe. Complications included 3 (5%) unplanned hospital admissions, 2 cases of respiratory failure, and 2 cases of pneumothorax.

Schroeder et al. (2010) reported findings from a prospective study with 52 patients who underwent placement of fiducial markers using ENB.16 All patients had peripheral lung tumors; 47 patients had inoperable tumors and 5 patients refused surgery. Patients were scheduled to receive tumor ablation using the stereotactic radiosurgery, which involved fiducial marker placement. The procedures were considered successful if the markers remained in place without migration during the timeframe required for radiosurgery. A total of 234 fiducial markers were deployed. Radiosurgery planning CT scans were performed between 7 and 14 days after fiducial marker placement. The planning CT scans showed that 215 (99%) of 217 coil spring markers and 8 (47%) of 17 linear markers remained in place, indicating a high success rate for coil spring markers. Three patients developed pneumothorax; 2 were treated with chest tubes, and 1 received observation only.

An advantage of ENB is that it allows the placement of pleural dye and/or fiducial markers in the same procedure as ENB-guided lung lesion biopsy, thereby reducing the need for a second procedure and potentially reducing risks to the patient. For example, in NAVIGATE, all but 39 of the patients had lung lesion biopsy or pleural dye marking during the same procedure.21 Patients being treated with targeted radiation are typically those with advanced respiratory disease who cannot undergo surgical resection. They are also more at risk for pneumothorax and resultant further complications. As the markers need to be near and not necessarily in a lesion, the accuracy advantage of a transthoracic approach is outweighed by the safety advantage of ENB over a transthoracic approach.

Section Summary: Electromagnetic Navigation Bronchoscopy to Aid in Placement of Fiducial Markers Prior to Treatment
There is only 1 study comparing ENB with another method of fiducial marker placement, and only 8 patients in that study who had markers placed with ENB had data available. There are several case series. In the largest series, a subgroup analysis of 258 patients from the NAVIGATE study, the subjective assessment of outcome was that 99.2% of markers were accurately placed and 94.1% were retained at follow-up (mean 8.1 days postprocedure). Pneumothorax of any grade occurred in 5.4%% of patients, and grade 2 or higher pneumothorax occurred in 3.1%.

Summary of Evidence
For individuals who have suspicious peripheral pulmonary lesion(s) when flexible bronchoscopy alone or with endobronchial ultrasound are inadequate to sample the pulmonary lesion(s), the evidence includes meta-analyses, a randomized controlled trial, and uncontrolled observational studies. A 2020 meta-analysis of 40 studies and a 2015 meta-analysis of 17 studies of ENB reported a large pooled positive likelihood ratio but a small negative likelihood ratio (0.2 to 0.22 ). Similarly, a 2014 meta-analysis of 15 studies found that navigation success was high, but diagnostic yield (64.9; 95% confidence interval 59.2 to 70.3) and negative predictive value (52.1; 95% confidence interval 43.5 to 60.6) were relatively low. The systematic reviews assessed the methodological quality of the evidence as low. Results from 2 large prospective multicenter uncontrolled studies, AQuiRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) and NAVIGATE (Clinical Evaluation of superDimension Navigation System for Electromagnetic Navigation Bronchoscopy), provide information about test characteristics and safety of ENB. An analysis of more than 500 patients included in the AQuiRE registry found a diagnostic yield of ENB that was lower than in other studies, and lower than bronchoscopy without ENB or endobronchial ultrasound. In the US cohort of the NAVIGATE study, the 12-month diagnostic yield was 72.9%. Overall, 4.3% of patients experienced pneumothorax, and pneumothorax requiring hospitalization or intervention occurred in 35 of 1,215 patients (2.9%). Bronchopulmonary hemorrhage overall occurred in 2.5% of patients overall and Common Terminology Criteria for Adverse Events grade 2 or higher in 1.5%. There were no deaths related to the ENB device. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have enlarged mediastinal lymph nodes who receive ENB with flexible bronchoscopy, the evidence includes a randomized controlled trial and observational studies. Relevant outcomes are test accuracy and validity, other test performance measures, and treatment-related morbidity. There is less published literature on ENB for diagnosing mediastinal lymph nodes than for diagnosing pulmonary lesions. One randomized controlled trial identified found higher sampling and diagnostic success with ENB-guided transbronchial needle aspiration than with conventional transbronchial needle aspiration. Endobronchial ultrasound , which has been shown to be superior to conventional transbronchial needle aspiration, was not used as the comparator. The randomized controlled trial did not report the diagnostic accuracy of ENB for identifying malignancy, and this was also not reported in uncontrolled studies. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have lung tumor(s) who need fiducial marker placement prior to treatment when flexible bronchoscopy alone or with endobronchial ultrasound are inadequate to place the markers near the pulmonary lesion(s), the evidence includes 1 comparative observational study and several case series. Relevant outcomes are health status measures and treatment-related morbidity. In the largest series, a subgroup analysis of 258 patients from the NAVIGATE study, the subjective assessment of outcome was that 99.2% of markers were accurately placed and 94.1% were retained at follow-up (mean 8.1 days postprocedure). Pneumothorax of any grade occurred in 5.4% of patients, and grade 2 or higher pneumothorax occurred in 3.1%. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. 

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2019 Input
Clinical input was sought to help determine whether the use of electromagnetic navigation bronchoscopy (ENB) with flexible bronchoscopy for individuals with suspicious peripheral pulmonary lesion(s), for individuals with enlarged mediastinal lymph node(s), and for individuals with lung tumor(s) who need fiducial marker placement prior to treatment would provide a clinically meaningful improvement in the net health outcome and whether the use is consistent with generally accepted medical practice. In response to requests, clinical input was received from 2 specialty society respondents offering a combined society-level response on behalf of both organizations, including input from physicians with academic medical center affiliations.

For individuals who have suspicious peripheral pulmonary lesion(s) who receive ENB with flexible bronchoscopy, clinical input supports this use and provides a clinically meaningful improvement in net health outcome and indicates this use is consistent with generally accepted medical practice in a subgroup of appropriately selected patients. Clinical input states that ENB is generally reserved for the most difficult patients, who are poor or borderline candidates for surgery and transthoracic sampling. In this context, the "low yield" observed in observational studies was actually high for this highly selected population. ENB, when used as an option in the armamentarium of the bronchoscopist, is a highly useful and low-risk modality for proper diagnosis and staging of lung cancer. For example, patients who are able to achieve a positive biopsy result through ENB benefit by getting a diagnostic result to appropriately guide treatment while avoiding transthoracic needle biopsy which has a 2 to 4 times higher risk of pneumothorax than a bronchoscopic biopsy approach.

For individuals who have enlarged mediastinal lymph node(s) who receive ENB with flexible bronchoscopy, clinical input does not support a clinically meaningful improvement in net health outcome and does not indicate this use is consistent with generally accepted medical practice. Clinical input states that mediastinal lymph node diagnosis was an early indication for ENB which has been largely replaced by endobronchial ultrasound. One could consider it in the uncommon scenario in which linear endobronchial ultrasound is not available and the patient is already having an ENB procedure for a peripheral nodule.

For individuals who have lung tumor(s) who need fiducial marker placement prior to treatment who receive ENB with flexible bronchoscopy, clinical input supports this use and provides a clinically meaningful improvement in net health outcome and indicates this use is consistent with generally accepted medical practice in a subgroup of appropriately selected patients. Clinical input states that the key advantage of ENB placement is the markedly reduced risk of pneumothorax compared to the transthoracic approach. Patients being treated with targeted radiation are typically those with advanced respiratory disease who cannot undergo surgical resection. They are also more at risk for pneumothorax and resultant further complications. As the markers need to be near and not necessarily in a lesion, the accuracy advantage of a transthoracic approach is outweighed by the safety advantage of ENB over a transthoracic approach.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in ‘Supplemental Information’ if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

National Comprehensive Cancer Network
Current National Comprehensive Cancer Network ( v.4.2021 ) practice guidelines on non-small-cell lung cancer state that the strategy for diagnosing lung cancer should be individualized and the least invasive biopsy with the highest diagnostic yield is preferred as the initial diagnostic study.22

  • "Patients with central masses and suspected endobronchial involvement should undergo bronchoscopy.
  • Patients with peripheral (outer one-third) nodules may benefit from navigational bronchoscopy, radial EBUS (endobronchial ultrasound), or transthoracic needle aspiration...
  • Patients with suspected nodal disease should be biopsied by EBUS, EUS [endoscopic ultrasound], navigation biopsy, or mediastinoscopy."

American College of Chest Physicians
In 2013, the American College of Chest Physicians updated its guidelines on the diagnosis of lung cancer.23 Regarding electromagnetic navigation bronchoscopy, the guidelines stated: "In patients with peripheral lung lesions difficult to reach with conventional bronchoscopy, electromagnetic navigation guidance is recommended if the equipment and the expertise are available." The College noted that the procedure can be performed with or without fluoroscopic guidance and has been found to complement radial probe ultrasound. The strength of evidence for this recommendation was grade 1C ("strong recommendation, low- or very-low-quality evidence").

U.S. Preventive Services Task Force Recommendations
Not applicable. 

Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in May 2021 did not identify any ongoing or unpublished trials that would likely influence this review.

References:

  1. Rivera MP, Mehta AC. Initial diagnosis of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. Sep 2007; 132(3 Suppl): 131S-148S. PMID 17873165
  2. Tape TG. Solitary Pulmonary Nodule. In: Black ER, et al, eds. Diagnostic strategies for common medical problems, 2nd edition. Philadelphia, PA: American College of Physicians; 1999.
  3. Wiener RS, Wiener DC, Gould MK. Risks of Transthoracic Needle Biopsy: How High?. Clin Pulm Med. Jan 01 2013; 20(1): 29-35. PMID 23525679
  4. 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. May 22 2020. PMID 32450240
  5. Zhang W, Chen S, Dong X, et al. Meta-analysis of the diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules. J Thorac Dis. May 2015; 7(5): 799-809. PMID 26101635
  6. 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): 165-76. PMID 24401166
  7. 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. Jul 01 2007; 176(1): 36-41. PMID 17379850
  8. Khandhar SJ, Bowling MR, Flandes J, et al. Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study. BMC Pulm Med. Apr 11 2017; 17(1): 59. PMID 28399830
  9. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic Navigation Bronchoscopy for Peripheral Pulmonary Lesions: One-Year Results of the Prospective, Multicenter NAVIGATE Study. J Thorac Oncol. Mar 2019; 14(3): 445-458. PMID 30476574
  10. Ost DE, Ernst A, Lei X, et al. Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry. Am J Respir Crit Care Med. Jan 01 2016; 193(1): 68-77. PMID 26367186
  11. Chee A, Stather DR, Maceachern P, et al. Diagnostic utility of peripheral endobronchial ultrasound with electromagnetic navigation bronchoscopy in peripheral lung nodules. Respirology. Jul 2013; 18(5): 784-9. PMID 23521707
  12. Diken OE, Karnak D, Ciledag A, et al. Electromagnetic navigation-guided TBNA vs conventional TBNA in the diagnosis of mediastinal lymphadenopathy. Clin Respir J. Apr 2015; 9(2): 214-20. PMID 25849298
  13. Wilson DS, Bartlett BJ. Improved diagnostic yield of bronchoscopy in a community practice: combination of electromagnetic navigation system and rapid on-site evaluation. J Bronchology Interv Pulmonol. 2007;14(4):227- 232.
  14. Kupelian PA, Forbes A, Willoughby TR, et al. Implantation and stability of metallic fiducials within pulmonary lesions. Int J Radiat Oncol Biol Phys. Nov 01 2007; 69(3): 777-85. PMID 17606334
  15. Anantham D, Feller-Kopman D, Shanmugham LN, et al. Electromagnetic navigation bronchoscopy-guided fiducial placement for robotic stereotactic radiosurgery of lung tumors: a feasibility study. Chest. Sep 2007; 132(3): 930-5. PMID 17646225
  16. 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. Nov 2010; 140(5): 1137-42. PMID 20850809
  17. 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. Jul 2015; 81(7): 659-62. PMID 26140883
  18. 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. Apr 2014; 21(2): 123-30. PMID 24739685
  19. Minnich DJ, Bryant AS, Wei B, et al. Retention Rate of Electromagnetic Navigation Bronchoscopic Placed Fiducial Markers for Lung Radiosurgery. Ann Thorac Surg. Oct 2015; 100(4): 1163-5; discussion 1165-6. PMID 26228602
  20. Rong Y, Bazan JG, Sekhon A, et al. Minimal Inter-Fractional Fiducial Migration during Image-Guided Lung Stereotactic Body Radiotherapy Using SuperLock Nitinol Coil Fiducial Markers. PLoS One. 2015; 10(7): e0131945. PMID 26158847
  21. 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. Jan-Dec 2019; 13: 1753466619841234. PMID 30958102
  22. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer. Version 5.2020. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed May 28, 2020.
  23. Detterbeck FC, Mazzone PJ, Naidich DP, et al. Screening for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. May 2013; 143(5 Suppl): e78S-e92S. PMID 23649455 

Coding Section

Codes Number Description
CPT 31626 Bronchoscopy, rigid or flexible, including fluoroscopic guidance when performedl with placement of fiducial makers, signle or multiple
  31627 Bronchoscopy, rigid or flexible, including fluoroscopic guidance when performedl with computer-assisted, image-guided navigation (List separately in addition to code for primary procedure)
ICD-9-CM Diagnosis   Investigational for all relevant codes
HCPCS A4648 Tissue marker, implantable, any type, each
ICD-10-CM (effective 10/01/15)   Investigational for all relevant codes
  C34.00-C34.92 Malignant neoplasm of bronchus and lung code range
ICD-1-PCS (effective 10/01/15)   ICD-10-PCS codes are only used for impatient services. There is no specific ICD-10-PCS code for this procedure
  0BB38ZX, 0BB38ZZ, 0BB48ZX, 0BB48ZZ, 0BB58ZX, 0BB58ZZ, 0BB68ZX, 0BB68ZZ, 0BB78ZX, 0BB78ZZ, 0BB88ZX, 0BB88ZZ, 0BB98ZX, 0BB98ZZ, 0BBB8ZX, 0BBB8ZZ, 0BBC8ZX, 0BBC8ZZ, 0BBD8ZX, 0BBD8ZZ, 0BBE8ZX, 0BBE8ZZ, 0BBF8ZX, 0BBF8ZZ, 0BBG8ZX, 0BBG8ZZ, 0BBH8ZX, 0BBH8ZZ, 0BBJ8ZX, 0BBJ8ZZ, 0BBK8ZX, 0BBK8ZZ, 0BBL88ZX, 0BBL8ZZ, 0BBM8ZX, 0BBM8ZZ Surgical, respiratory system, excision, via natural or artificial opening endoscopic, code by body part and whether it is diagnostic or not
  0BJK8ZZ, 0BJL8ZZ  Surgical, respiratory system, inspection, via natural or artificial opening endoscopy, code by lung right or left
Type of Service  Surgical   
Place of Service  Outpatient/Inpatient   

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

Index
Bronchoscopy, electromagnetic navigation
Electromagnetic navigation, bronchoscopy

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2013 Forward     

02/11/2022 

Interim review updating description, no change to policy intent. 

12/01/2021 

Annual review, no change to policy intent. Updating rationale and references. 

12/01/2020 

Annual review, no change to policy intent. Updating policy verbiage/format for clarity. Also updating rationale and references. 

12/03/2019 

Annual review, no change to policy intent. Adding regulatory status, updating guidelines. 

07/23/2019 

Interim review, policy entirely revised to allow services as medically necessary that were previously investigational in nature. 

12/19/2018 

Annual review, no change to policy intent. Updating background, rationale, references and coding. 

12/12/2017 

Annual review, no change to policy intent. Updating background, rationale and references. 

12/01/2016 

Annual review, no change to policy status. Updating background, description, guidelines, rationale and references. 

11/23/2015 

Annual review, no change to policy intent. Updating background, description, rationale, references and related policies. 

12/01/2014

Annual review. No change to policy intent. Added keywords, coding, policy guidelines, benefit applications. Updated rationale and references.

11/11/2013

Annual review,added related policies, updated rationale and references.

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