Electromagnetic Navigation Bronchoscopy
Electromagnetic navigation bronchoscopy is considered investigational for the placement of fiducial markers.
Electromagnetic navigation bronchoscopy (ENB) is intended to enhance standard bronchoscopy by providing a three-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 undergo biopsy and to allow for placement of fiducial markers.
Pulmonary nodules are identified on plain chest radiographs or chest CT scans. Although most of these nodules are benign, some are cancerous, and early diagnosis of lung cancer is desirable because of the poor prognosis when it is diagnosed later in the disease course. The method used to diagnose lung cancer depends on a number of factors, including lesion size and location, as well as the clinical history and status of the patient. There is generally greater diagnostic success with centrally located and larger lesions.
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 them; none of the methods are ideal for safely and accurately diagnosing malignant disease. 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 evaluating 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, less than 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 24% 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 small lesions less than 1 cm in size. Lung biopsy is the criterion standard for diagnosing pulmonary nodules but is an invasive procedure. (1,2)
Recent advances in technology have led to enhancements that may increase the yield of established diagnostic methods. CT 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 (EBUS) by radial probes, previously used in the perioperative staging of lung cancer, can also be used to locate and guide sampling of peripheral lesions. EBUS is reported to increase the diagnostic yield of flexible bronchoscopy to at least 82%, regardless of the size and location of the lesion. (1)
Another proposed enhancement to standard bronchoscopy is electromagnetic navigation bronchoscopy (ENB). This technology uses CT scans to improve the ability of standard bronchoscopic procedures to reach lesions in the periphery of the lungs. The InReach™ system was the first ENB system cleared for marketing by FDA. The three phases of the procedure using the InReach system are as follows:
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. In addition, 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.
Several additional navigation software-only systems have been cleared for marketing by FDA through the 510(k) process. These include:
FDA product codes: JAK and LLZ
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The policy was created in November 2009 and was based on a review of the scientific literature. The policy was updated regularly with searches of the MEDLINE database. Most recently, the literature was reviewed through November 3, 2014. The literature on use of electromagnetic navigation bronchoscopy (ENB) as a diagnostic aid and for placement of fiducial markers is described next.
ENB for the Diagnosis of Pulmonary Lesions and Mediastinal Lymph Nodes
Evaluation of electromagnetic navigation bronchoscopy as a diagnostic tool involves examining the:
A comprehensive systematic review of the literature was published in 2014 by Gex et al. (3) The investigators included 15 studies that enrolled at least 10 patients and reported the diagnostic yield of ENB for peripheral lung nodules. Fourteen of the 15 studies used the SuperDimension ENB system and the remaining study used a commercially unavailable system. Together, the 15 studies included 971 patients with a total of 1033 lung nodules; the median number of nodules per study was 50 (range, 13-271). The median prevalence of malignancy was 77.5% (range, 56.5-92.3%). The studies confirmed the diagnosis using surgical resection, alternative biopsy techniques, and/or extended follow-up as the reference standard. The authors used the QUADAS tool to evaluate the methodologic quality of included studies, and overall quality was poor. None of the studies compared ENB with surgery, and selection criteria were rarely clearly specified. According to the investigators, it was unclear whether study participants were representative of the patients who would undergo ENB in an actual clinical setting.
The authors reported 7 outcomes. Due to heterogeneity among studies, they extracted the actual results of ENB from each study and used random effects models. Their pooled analyses are reported in Table 1.
Table 1. Meta-Analysis of Electromagnetic Navigation Bronchoscopy Performance Reported by Gex et al. (2014)
Although the navigation success rate using ENB was generally very high, the diagnostic yield and NPV were relatively low. The authors proposed several factors that might help explain this discrepancy. ENB data are based on a virtual spatial reconstruction and the actual location may differ substantially, leading to an inability to sample the lesion after an apparently successful navigation. Moreover, when nodules are extrabronchial, the sampling tool will tend to follow the bronchus and miss the nodule even when the sampling tool has reached the immediate vicinity of the nodule. (The authors noted that this limitation may be corrected by use of newer curved catheters).
The investigators also evaluated variables affecting the performance of ENB. Univariate analysis identified 6 variables that were significantly associated with diagnostic yield in at least 1 study: location of the lower lobe decreased yield; and greater nodule size, presence of a bronchus sign, lower registration error, nodule visualization with an EBUS probe, and catheter suction technique increased yield.
The authors also reported that in their analysis, the pneumothorax rate following ENB was 3.1%, and 1.6% of patients required chest tube placement for treatment of pneumothorax.
A previous meta-analysis published in 2011 by Wang Memoli et al evaluated the diagnostic yield of guided bronchoscopy techniques for evaluating pulmonary nodules (including ENB and endobronchial ultrasound [EBUS], among others). (4) To be included in the review, studies needed to evaluate diagnostic yield and include more than 5 patients; studies could be prospective or retrospective. A total of 11 studies on ENB met the inclusion criteria. The pooled diagnostic yield was 67.0% (95% confidence interval [CI], 62.6% to 71.4%), similar to the pooled estimate in the 2014 Gex meta-analysis. The authors did not report adverse events associated with individual guidance techniques; the overall pooled pneumothorax rate was 1.6%.
Randomized Controlled Trials
Eberhardt et al published the only randomized controlled trial (RCT) to date evaluating ENB for the diagnosis of pulmonary nodules. (5) This study consistently used surgical biopsy as a criterion standard confirmation of diagnosis. Patients were randomized to receive ENB only, EBUS only, or the combination of ENB and EBUS. Whereas ENB is designed to help navigate to the target but cannot visualize the lesion, EBUS is not able to guide navigation but enables direct visualization of the target lesion before biopsy. The study included 120 patients who had 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 diagnostic yield, defined as the ability to yield a definitive diagnosis consistent with clinical presentation. If transbronchial lung biopsy was not able to provide a diagnosis, patients were referred for surgical biopsy. The mean (SD) size of the lesions was 26 (6) 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 EBUS only, and 88% (35/40) with combined ENB/EBUS; the yield was significantly higher in the combined group. The NPV for malignant disease was 44% (10/23) with ENB only, 44% (7/16) with EBUS only, and 75% (9/12) with combined ENB/EBUS. Note that the number of cases was small, and thus the NPV is an imprecise estimate. Moreover, the authors stated in the discussion that the yield in the ENB-only group is somewhat lower than in other studies and attribute this to factors such as the use of forceps for biopsy (rather than forceps and endobronchial brushes) and/or an improved diagnosis using a criterion standard. The pneumothorax rate was 6%, which did not differ significantly among the 3 groups.
A number of prospective and retrospective case series using ENB have been published. Selected representative series are described next.
In a large series published in 2007, Wilson et al reviewed the records of 248 consecutive patients who were referred for evaluation of suspicious peripheral lung lesions, enlarged mediastinal lymph nodes, or both. (6) There was no consistent protocol for confirming diagnosis, although the authors stated that most patients were followed up for confirmation of diagnosis. ENB was used to locate, register, and navigate to lung lesions. Once navigation was completed, fluoroscopic guidance was used to verify its accuracy and to aid in the biopsy or transbronchial needle aspiration. Forceps were used to sample lung lesions. The mean size of the targeted peripheral lung lesions was 21 (14) mm. A total of 266 of 279 (95%) of the targeted peripheral lung lesions and 67 of 71 (94%) of the lymph nodes were successfully reached, and tissue samples for biopsy were obtained from all of these. The primary study outcome was diagnostic yield on the day of the procedure; this was obtained for 151 of 279 (54%) of the peripheral lung lesions that were reached and 64 of 67 of the lymph nodes that were reached. Ninety of the lung lesions were malignant, and 61 were benign. Another 16 peripheral lung lesions were followed-up and later confirmed as true negatives. The final status of 89 lesions (~30% of the targeted lesions) was inconclusive. There were 8 complications: 3 cases of moderate bleeding (none required transfusion), 3 cases of pneumothorax (none required treatment), 1 case of hematoma (did not require treatment), and 1 case of pneumonia/chronic obstructive pulmonary disease exacerbation (treated on outpatient basis).
In a 2007 prospective study, Eberhardt et al. reported on 89 patients who underwent ENB. (7) All patients had evidence of peripheral lung lesions or solitary pulmonary nodules without evidence of endobronchial pathology. The mean (SD) size of the targeted lesions was 24 (8) mm. ENB yielded a definitive diagnosis in 52 lesions, and another 10 lesions that were followed up for a mean of 16 months appear to have been true negatives. The authors reported a specificity of 100% and an NPV for malignant disease of 44%. Complications included 2 asymptomatic cases of pneumothorax that were identified; no treatment was necessary.
A 2013 prospective study by Chee et al in Canada investigated the use of ENB in cases where peripheral EBUS alone was unable to obtain a diagnosis. (8) The study included 60 patients with peripheral pulmonary lesions. Patients either had a previous negative CT-guided biopsy or did not have a CT-guided biopsy due to technical difficulties. An attempt was first made to identify the lesion using peripheral EBUS and, if the lesion was not identified, then an ENB system was used. Nodules were identified on ultrasound image by EBUS alone in 45 of 60 cases (75%). ENB was used in 15 cases (25%), and in 11 of these cases (73%), the lesion was identified. Peripheral EBUS led to a diagnosis in 26 cases and ENB in an additional 4 cases, for a total diagnostic yield of 30 of 60 cases (50%). The extent of improved diagnosis with ENB over EBUS 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.
The evidence on ENB for diagnosis of pulmonary lesions is insufficient. A 2014 meta-analysis of 15 studies (only 1 of which was an RCT) judged the quality of most published studies to be low. Findings of the meta-analysis were that navigation success was high, but diagnostic yield and the clinically important parameter of NPV, were relatively low. There are less data on the potential use of ENB in biopsy of mediastinal lymph nodes. Moreover, due to the small number of patients in individual studies, there is limited evidence on complications from the procedure and adverse effects such as pneumothorax. Studies have not compared clinically significant pneumothorax rates with ENB versus needle biopsy. The data are also insufficient to identify potential patient selection criteria. The 2014 meta-analysis identified lack of clear selection criteria as a key potential bias in the published literature. Overall, the evidence is insufficient to determine the added benefit of ENB compared with standard techniques for diagnosing of pulmonary lesions and mediastinal lymph nodes.
ENB for the Placement of Fiducial Markers
Evaluation of ENB as an aid to placement of fiducial markers involves searching for evidence that there are better clinical outcomes when ENB is used to place markers than either when fiducials are placed using another method or when no fiducial markers are used. This policy only evaluates the use of ENB to place fiducial markers; it does not evaluate the role of fiducial markers in radiotherapy.
Three studies were identified; there were no RCTs. Only one of the trials compared fiducial marker placement with ENB with another method of fiducial marker placement. This study, by Kupelian et al included 28 patients scheduled for radiotherapy for early-stage lung cancer. (9) 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 using the superDimension system. At least one marker was placed successfully within or near a lung tumor in all patients. The fiducial markers did not show substantial migration during the course of treatment with either method of marker placement. The only clinical outcome reported was rate of pneumothorax; 8 of 15 patients with transcutaneous placement developed pneumothorax, 6 of which required chest tubes. In contrast, none of the 8 patients with transbronchial placement developed pneumothorax.
A study by Anantham et al included 9 patients with peripheral lung tumors who were considered nonsurgical candidates and were scheduled to undergo treatment with robotic stereotactic radiosurgery (CyberKnife). (10) Using the SuperDimension InReach™ system, 39 fiducial markers were successfully placed in 8 of the 9 patients. A total of 35 of the 39 markers (90%) were still in place at radiosurgery planning 7 to 10 days later. No complications were observed.
In 2010, Schroeder et al reported on findings from a single-center prospective study with 52 patients who underwent placement of fiducial markers using ENB with the InReach™ system. (11) Patients all had peripheral lung tumors; 47 patients had inoperable tumors and 5 patients refused surgery. Patients were scheduled to receive tumor ablation using the CyberKnife stereotactic radiosurgery, which involves 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; 17 linear fiducial markers in 4 patients and 217 coil spring fiducial markers in 49 patients. CyberKnife planning CT scans were performed between 7 and 14 days after fiducial marker placement. The planning CT scans showed that 215 of 217 coil spring markers (99%) and 8 of 17 linear markers (47%) 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.
There is insufficient evidence to determine the safety and efficacy of ENB used for fiducial marker placement. There are only a few published studies with small numbers of patients and only one study compared ENB with another method of fiducial marker placement.
Summary of Evidence
Electromagnetic navigation bronchoscopy (ENB) uses computed tomography scans to improve the ability of standard bronchoscopic procedures to reach lesions in the periphery of the lungs. Overall, data are insufficient to determine the risks and benefits of ENB compared with standard approaches to diagnose peripheral lesions. The data are also insufficient to identify which patients might benefit from ENB. Eligibility criteria of existing studies were variable, and in some cases, not well-defined; it is not clear whether this would be most appropriate as a first-line or second-line diagnostic approach. In addition, insufficient data are available on the safety and efficacy of ENB used for fiducial marker placement. There are only a few small studies, and only one compared ENB with another method of fiducial marker placement. Guidelines published in 2013 suggest ENB as an option for patients with peripheral lung lesions, but these recommendations are not based on high-quality evidence demonstrating improved outcomes. Thus, use of this technology is considered investigational.
Practice Guidelines and Position Statements
National Comprehensive Cancer Network (NCCN)
The National Comprehensive Cancer Network (NCCN) clinical practice guideline on non-small-cell lung cancer V1.2015 states 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.(12)
American College of Chest Physicians
In 2013, the American College of Chest Physicians issued updated guidelines on the diagnosis of lung cancer. (13) Regarding ENB, the guideline 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 authors 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 as Grade 1C, defined as “Strong recommendation, low- or very-low-quality evidence.”
British Thoracic Society
In 2011, the British Thoracic Society published a guideline on advanced diagnostic and therapeutic flexible bronchoscopy in adults. (14) The guideline included the following recommendation: “Electromagnetic bronchoscopy may be considered for the biopsy of peripheral lesions or to guide transbronchial needle aspiration for sampling mediastinal lymph nodes.” This was a “Grade D” recommendation, meaning that it is based on non-analytic studies, e.g., case series or expert opinion, or based on extrapolated data from observational studies.
U.S. Preventive Services Task Force Recommendations
Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers.
Bronchoscopy, rigid or flexible, including fluoroscopic guidance when performed; with computer-assisted, image-guided navigation (List separately in addition to code for primary procedure)
Note: Special considerations for reporting the procedure:
CPT code 31627 is an add-on code that is used in conjunction with CPT codes 31615, 31622-31631, 31635, 31636, and 31638-31643.
CPT code 31627 includes 3-dimensional reconstruction, and is not reported with CPT codes 76376 and 76377.
Type of Service
Place of Service
Add to Surgery Section - New Policy
Replace Policy - Policy updated with literature search through December 2010. No change to policy statements. References 8, 9, 10 and 13 added; other references renumbered. ICD-10 codes added.
Replace policy. Policy updated with literature search through November 2011. No change to policy statements. References 10 and 14 added; other references renumbered or removed.
Update Related Policy – Add 6.01.41; ICD-10 codes are now effective 10/01/2014.
Replace Policy. Title now: “Electromagnetic Navigation Bronchoscopy”. Rationale section updated based on a literature search through November 2012. References 5, 8 and 9 added; other references renumbered or removed. Policy statement unchanged.
Update Related Policies. Remove 6.01.41 as it was archived.
Replace policy. Policy updated with literature search through November 26, 2013. No change to policy statements. References 8, 12, 16, and 17 added; other references renumbered or removed. HCPCS code A4648, and ICD-10 codes removed; these do not suspend on the RMN and are not utilized in adjudication of the policy.
Update Related Policies. Change title to 2.03.10.
Update Related Policies. Change title to 6.01.10.
Update Related Policies. Add 6.01.58.
Annual Review. Policy updated with literature review through November 3, 2014. Reference 3 added; others renumbered. Policy statements unchanged. CPT code 31626 removed from policy.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).