March20, 2023

Abstract Volume: 5 Issue: 5 ISSN:

Diagnostic Accuracy of Radial Probe Endobronchial Ultrasound in Peripheral Pulmonary Lesions: Systematic Review and Meta Analysis

Dr Neeraj Mumwalia1*, Dr Rahul Gupta2, Dr Harsh Vardhan Puri 3, Dr Prem Prakash Sharma4


1. Lecturer Chest Diseases, Department of Pulmonary Medicine, Govt Medical College, Jammu, India

2. Professor and Head, Department of Pulmonary Medicine, Government Medical college, Jammu, India

3. Senior Consultant, Chest Onco Surgery and Lung Transplantation, Department of Thoracic Surgery, Institute of Chest Surgery, Medanta - The Medicity, Gurugram, India.

4. Associate Professor, Department of Community Medicine and Family Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Corresponding Author: Dr Neeraj Mumwalia, Lecturer (Chest Diseases), Department of Pulmonary Medicine, Govt Medical college Jammu, India.

Copy Right: © 2023 Dr Neeraj Mumwalia, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received Date: January 17, 2023

Published Date: February 01, 2023

DOI: 10.1027/marpy.2023.0225



Background: Increasing numbers of peripheral pulmonary lesions (PPLs) suggestive of early-stage lung cancer are being discovered thanks to lung cancer screening using computed tomography of the chest. PPLs may be sampled using radial endobronchial ultrasonography (R-EBUS) for early lung cancer diagnosis and treatment. Using R-EBUS has the potential to improve diagnostic accuracy, which justifies its use.

Objective: Examining how well R-EBUS performs in comparison to other diagnostic methods for PPLs was the focus of this research.

Methods: A meta-analysis and systematic review were performed. Original study providing a diagnostic accuracy of R-EBUS for PPLs found on computed tomography chest questionable for malignancy was sought for by a search of the Pubmed, Ovid, Cochrane, Medline, and Embase databases. I2 was used to measure the degree of dissimilarity between the studies. Diagnostic accuracy was aggregated using random effects models. Meta-regression was used to investigate the factors that contributed to the diversity of study results. The impact of publication bias and the size of studies were evaluated.

Results: One hundred trials involving 3204 patients and 5566 PPLs. Overall diagnostic accuracy for R-EBUS was 72.4% (95% CI: 68-76.1) Less than 2% of complications were seen across all localization methods.

Conclusion: High diagnostic accuracy is combined with a high rate of successful PPL localization when using the R-EBUS probe. Diagnostic algorithms are the most practical choice for healthcare authorities.

MeSH Keywords: Pulmonary Lesion, Pulmonary Nodule or Peripheral pulmonary Lesion, Lung nodules or Lung tumor, Lung Cancer or Pulmonary Cancer, Probe radial Endobronchial Ultrasound or R- EBUS.



R- EBUS: Radial Probe Endobronchial Ultrasound

PPLs: Peripheral Pulmonary Lesions

CT: Computed Tomography Scan

CT- TTNB: Computedtomography guidedtransthoracicneedlebiopsy

ACCP: American College of Chest Physicians

ENB- Electromagnetic Navigational Bronchoscopy

PRISMA: Preferred Reporting Items for Systematic reviews and Meta-analysis

QUADAS: Quality Assessment of Diagnostic Accuracy Studies

CI: Confidence Intervals

Diagnostic Accuracy of Radial Probe Endobronchial Ultrasound in Peripheral Pulmonary Lesions: Systematic Review and Meta Analysis



CT (chest lung cancer) screening programs in Europe are detecting an increasing number of peripheral pulmonary lesions (PPLs) in current and past smokers that are suspicious for early-stage lung cancer (McWilliams et al., 2013; While et al., 2016). For PPLs larger than 8 mm in these high-risk individuals, current clinical practise recommendations advise additional diagnostic examination (Postmus et al., 2017). According to data from the National Lung Screening Trial (NLST), screening computed tomography (CT) of the chest has a false-positive (FP) PPL rate that may approach 96.4%. This emphasises the need of a reliable histologic diagnosis of lung cancer for guiding lesion care and determining which patients would gain the most from curative-intent surgical lung resection (Ding et al., 2022). Also, some people with early-stage lung cancer may be medically inoperable because of other health issues or because they have inadequate lung function. Noninvasive local treatments, such as external-beam radiation therapy, are an option in certain situations, but only if a proper diagnosis has been made (Rowell & Williams, 2001).

Traditional biopsy techniques for PPL diagnosis include transbronchial biopsy guided by fluoroscopy and computed tomography of the chest-guided transthoracic needle biopsy (CT-TTNB).  Care for patients with PPL is no longer recommended to be based only on flexible bronchoscopy as stated in the recommendations published by the American College of Chest Physicians (ACCP). This is related to its poor diagnostic yield, particularly for PPLs smaller than 20 mm in diameter and those with nonsolid density on CT of the chest (Planchard et al., 2019).Tobacco smokers with emphysema have additional hazards during CT-TTNB, including pneumothorax (collapse of the lung tissue), hemorrhage, and radiation overexposure (Lee et al., 2022).


Image-assisted diagnostic tools for use with flexible bronchoscopy have been developed to improve diagnostic accuracy and patient safety as more peripheral lung nodules suspected for malignancy are found via lung cancer screening programmes. Bronchoscopy guided by radial endobronchial ultrasound (R-EBUS) is one example (Zheng et al., 2022).

Evaluation of peripheral lung lesions that cannot be accessed by conventional flexible bronchoscopy with R-EBUS is indicated in the ACCP recommendations for the diagnosis and treatment of lung cancer (Kurihara et al., 2022).Due to the high cost of ENB consumables per case in a single-payer public healthcare system, R-EBUS has a greater reach in Canada (McGuire et al., 2020).

The R-EBUS procedure for PPL biopsy entails inserting a micro (20-MHz) ultrasonic probe of 1.4 millimetres in diameter into the working channel of a flexible bronchoscope. This creates the opportunity for direct circular contact to be made with the small peripheral airways. This allows for the surrounding pulmonary structures and PPL to be seen by ultrasonography, which in turn makes it possible to do a biopsy with either forceps or an aspiration needle or cytology brush. R-EBUS offers the advantage of enhancing PPL diagnostic yield while eliminating radiation exposure from fluoroscopy or CT guided needle biopsy, in comparison to traditional flexible bronchoscopy and transbronchial biopsy (Jiang et al., 2020). When compared with CT-TTNB, the number of reports of concomitant bleeding and pneumothorax is likewise much reduced with R-EBUS (Jiang et al., 2020).

Combining computerized bronchoscopy airway architecture is required in order to perform R-EBUS for peripheral lung lesion biopsy, as explained in further detail by Tang et al. (2020).

It is allowed to get a visualization of the PPL and adjacent lung tissues while performing a biopsy. There are a number of studies that have been conducted at a single site and have reported the diagnostic yields and the rates of procedure complications for R-EBUS. In the past, a meta-analysis evaluating these outcomes was performed using one meta-analysis for each modality, respectively (Toennesen et al., 2022).On the other hand, the test performance features of these various PPL localization systems have not been compared for the purpose of discussion in meta-analysis. At addition, after the release of the earlier findings, a number of additional studies that evaluated the effectiveness of R-EBUS in a single center and were reviewed by experts in the field have been made public.


The major purpose of this study is to evaluate the relative effectiveness of R-EBUS biopsy in terms of successful localization and diagnostic accuracy. The secondary purpose is to identify the incidence of problems linked to biopsies for each method.


Radial endobronchial ultrasound R-EBUS is not an accurate method for the biopsy/treatment of peripheral pulmonary lesions (PPLs).


The primary exposures that will be evaluated are those that are governed by R-EBUS and PPL. The primary health outcomes that need to be reported are the diagnostic accuracy and sensitivity of each sample technique for malignancy. Complication rates for each technology are one of the secondary outcomes that need to be reported (bleeding, pneumothorax, aspiration pneumonitis, and respiratory failure)

The results of this research might potentially be utilised to advise public health policy on the most effective image-guided way to discover peripheral pulmonary nodules that have been found on CT chest scans and get a biopsy of those nodules. The results of this study might potentially be included into clinical treatment algorithms for peripheral lung nodules that are discovered via CT lung cancer screening programmes.


Materials and Methods

Literature Search

The standard PRISMA procedure (Preferred Reporting Items for Systematic reviews and Meta-analysis), which was developed by the Cochrane Collaboration, served as a guide for both the systematic review and the meta-analysis that was conducted. To find all of the studies that employed R-EBUS as a therapy for peripheral pulmonary lesions (PPLs) seen on CT chest, an electronic systematic search of the medical literature was carried out. From 1948 through 2023, the databases Pubmed, Ovid, Cochrane, Medline, and Embase were searched using a predetermined keyword search approach (Table 1).  In order to locate any and all articles that could be suitable for incorporation, a comprehensive manual search of all references included within the primary articles and review papers was carried out. The search was restricted to research involving human participants and to those that were available in full-text form in English. The use of the systematic search method resulted in the discovery of a total of 1065 articles.

Selection Criteria

The criteria for selection were decided upon in advance, and then the abstracts of all 1065 articles were assessed in line with those criteria. All of the following criteria were met by the papers that were put forth for consideration as candidates for a full-text review: A minimum of five patients were enrolled in the study by me; (ii) the histologic diagnostic yield of R-EBUS was reported for peripheral pulmonary lesions; (iii) the existence of the peripheral pulmonary lesions was confirmed by CT chest; and (iv) the study population included patients who were thought to have malignant peripheral pulmonary lesions. Only the abstracts that were able to meet all of these criteria were allowed to go on to the full-text article review step. The reference lists of the publications that were considered for exclusion from the study were manually searched for potentially additional relevant articles that matched the criteria for study inclusion. Although reviews, editorials, nonpeer reviewed papers, and meta-analyses were not considered for inclusion in the research, these types of articles were not considered for inclusion in the research.

After going over the entire texts of the studies, the ones that used linear EBUS to sample the mediastinal lymph nodes, did not use R-EBUS to sample the peripheral pulmonary lesions, and focused primarily on benign diseases such as sarcoidosis were ruled out. In addition, studies were omitted from the final analysis if there was no reference standard used to compare the index test.


Study Quality Assessment

The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) method was used to evaluate the quality of the studies that were included in the review (Whiting et al., 2003).  The QUADAS tool consists of 14 elements, each of which is documented per study as "absent" or "present." These elements are as follows: sufficient index test description and reference; representative study sample spectrum; reported reasons for study participant withdrawals and loss to follow-up; relevant clinical information; index and reference test interpretation blinding; definition of positive test result; complete verification of diagnosis with independent reference standard; avoided clinical review bias; appropriate clinical information; and appropriate clinical information. A total quality score between 11 and 14 was rated "excellent," 7 to 10 was considered "average," and 6 was considered "poor." The QUADAS elements that were present each received a score of 1 (Whiting et al., 2003).


Data Extraction

Data were collected, to the extent that it was possible, on the following topics: study characteristics; a description of the study population; the results of the biopsy, which were categorized as positive (either malignant or benign), nondiagnostic, normal lung tissue, or reported as inconclusive, or as requiring further tissue confirmation (chronic inflammation, organizing pneumonia, or atypical cells); the complications, which were categorized as absent, bleeding that was self-limited (minor), topical treatment (moderate)

The following intervention methods were extracted: sedation type, the number of times a biopsy was attempted on each lesion, sample methodology, examination length, supplementary guiding strategies, and a histology reference standard.

In order to compute the following for R-EBUS, respectively, selected study biopsy performance results were retrieved and used (Whiting et al., 2003)

The findings of the index test (R-EBUS) and the reference test were used to classify the research participants, and two-by-two contingency tables were generated for each of the studies.

The data that were extracted were combined with weighted averages, where the weight of each research was determined by the size of its sample population.



Study Selection

1065 results came up during the comprehensive search (Fig. 1).  After going over the abstracts of each article, we ultimately decided to look at 220 of them in their entirety. Out of these, 120 were disregarded because they did not pertain to the use of R-EBUS in the diagnosis accuracy for the treatment of peripheral pulmonary lesions; they did not pertain to the diagnostic yields of these technologies; or they were not unique research (review articles or editorial commentaries).  At long last, the meta-analysis was down to just 100 papers (Charvez et al., 2015).


Study Description

The most significant findings of the study are broken down into categories and shown in tables 2 and 3. The total number of people who participated in the study of peripheral pulmonary lesions was 6379, and they had a total of 5566 lung lesions amongst them. The average age was 55 years old (and the standard deviation).  Many different countries were represented among the people who took part in the survey.

The maximal diameter of pulmonary lesions was measured to be 28.35 millimetres on average (standard deviation). The overall frequency of lung cancer was shown to be 70.33 %, according to the research.

Aurora system All of the R-EBUS studies utilised either the 20-MHz mechanical radial probe (XUM-S20– 17R; Olympus; Tokyo, Japan) with an external diameter of 1.4 mm (that is, a probe with an external diameter of 1.4 mm) or the 20-MHz mechanical radial-type probe (UMS20–20R; Olympus) with an external diameter of 1.7 mm (that is, a probe with an external diameter of 1.7 (Hautmann et al., 2005).  The diagnostic reference standard in a number of studies consisted of either surgical resection, other biopsy methods, or prolonged follow-up with CT chest.


Heterogeneity Assessment

The trials were determined to have a high degree of heterogeneity (I2 varied from 66-94% while P value was less than 0.001).  Overall and stratified by peripheral pulmonary lesions localization approach, values of sensitivity and other diagnostic characteristics for lung cancer were pooled using random-effects models. This action was taken because there was substantial evidence of study-to-study variation.

Study Quality and Bias

Total QUADAS scores were low, suggesting that the majority of included studies were of poor or intermediate quality in terms of their methodology (Fig. 2).  The average QUADAS score was 4.4, with a standard deviation of 0.4. (1.3).  The lowest possible score was 2, and the best was 7.

Confirmation of the lung lesion found by histology using a different means, such as surgery, was not part of the criteria that determined whether or not a research study reached the "gold standard." The testing carried out in comparison to the reference standard was not documented in sufficient detail to make a repeatable process possible. Even though the vast majority of studies claimed to have access to clinical patient data, it was difficult to do an analysis for selection bias since it was unclear whether or not research participants were typical of patients who had R-EBUS biopsies in clinical practise. It was also perplexing that there was a lack of clarity on the standardisation of processes for the interpretation of index and reference tests, such as observer blinding. An Egger funnel plot was used in order to evaluate the results of individual, underpowered study (Fig. 3).  Both the bottom symmetrical funnel plot and the Begg statistic P-value of 0.001 are powerful indications of very little study impacts that are associated with less accurate baseline evaluations.


Performance Outcomes

The diagnostic accuracy for the treatment of peripheral pulmonary lesions based on the given reference standard likewise varied greatly from research to study, ranging anywhere from 58.3% to 96.8%. The overall diagnostic accuracy of the pooled data for R-EBUS was 72.4% (95%, CI= 68.7-76.1).  Fig 4. depicts the forest plot that was used to determine the diagnosis accuracy.

Exploration of Heterogeneity

A meta-regression was carried out in order to investigate the factors that led to the heterogeneity. This showed that there was only a small amount of evidence to suggest that the covariates of (1) maximal nodule size (P=0.0695) and (2) biopsy method employed to sample the target lesion once it was localised (forceps, brush, or aspiration needle use, P=0.0572) contributed to the heterogeneity found between studies. There was evidence that was moderately strong (P=0.0450) that using multiple different biopsy methods for one lung lesion sampling procedure (for example, using forceps alone versus using forceps plus brushings) contributed to between-study heterogeneity. This was found in the context of a comparison between using forceps alone and using forceps plus brushings.


In none of the studies that were chosen, participants had significant bleeding that required surgical intervention to manage. There was one occurrence of pulmonary hematoma that was recorded and it was managed with careful surveillance (Wilson & Bartlett, 2007).  At the time of flexible bronchoscopy, there were no instances in which the patient had any little bleeding that was either self-limiting or needed the use of a simple topical hemostatic agent soon after the procedure. In order to treat the bleeding, chest tubes were not necessary. A topical treatment for bleeding that was applied promptly on the airway using the flexible bronchoscope, such as dilute epinephrine, was administered in 100 of the total occurrences of mild hemorrhage.




With regard to the successful PPL localization, a random-effects meta-analysis indicated an overall successful localization rate of R-EBUS 90.2%. The successful PPL localization rate was high for both technologies. The combination of the two methods showed a diagnostic accuracy of around 71% when used to the identification of malignant PPL on CT chest scans. When contrasted with the lower sample sizes of selected research, the R-EBUS estimate's 95% confidence intervals may indicate enhanced accuracy as a result of bigger lung nodule sample sizes. This is in contrast to the smaller sample sizes of certain of the studies.

If the physician who is doing the surgery does not have enough expertise in the application of all aspects of the technology used for localization and sampling, the performance of the diagnostic test will not be at its highest possible level.

The overall diagnosis accuracy with R-EBUS was 72.4%, taking into account both the malignant and benign diagnoses. Despite the fact that the %age is larger when compared to Probe R-EBUS, the 95% confidence intervals are much broader for this estimate, which indicates a lack of accuracy. This is again most likely owing to the limited sample size, which makes it more difficult to discern from the target lesion when using radial ultrasonography. In addition, this underlines how important it is to confirm a benign diagnosis using a secondary way of tissue diagnosis if there is a strong suspicion that the PPL on CT chest is malignant tissue (McGuire et al., 2020)



One of the limitations of this meta-analysis is that the majority of the studies that were made available for selection were of a low quality; the QUADAS scores of the investigations were used to establish the level of quality of the research. For example, several studies didn't have a trustworthy reference standard, which made it difficult to validate the R-EBUS test's performance characteristics. In addition, the reporting for either the index or the reference test was not carried out in a blind method.

The high degree of heterogeneity that occurred across the many investigations, as shown by the I2 statistic, is one of the things that holds this study back, making it one of its weaknesses. The importance of this study is still drawn from the methodical endeavours made to analyse, using meta-regression, the variables that lead to the heterogeneity that is demonstrated across studies. With the use of this technique, we are able to create precise explanations that explain the observed heterogeneity; nevertheless, we are unable to quantify the exact amount to which each discovered variable contributes to the overall effect. We were able to determine, via the use of meta-regression, that the observed between-study heterogeneity was the result of a mixture of variables; these factors included, but were not limited to, the size of the PPLs as well as the sampling strategy (forceps, needle, brush)

There were also hints of publishing bias favouring more limited research, as the funnel diagram in Figure 3 indicates. The bulk of the studies that were selected had a limited number of participants in their samples, therefore the accuracy of their estimations was severely compromised. Because of this, the pooled and stratified study estimates that were observed had a lower degree of accuracy than they otherwise would have had. Due to the fact that we wanted for this to be the most in-depth evaluation and analysis possible, we felt that it was essential to include analyses of some of the less popular series. It is possible that integrating these studies will be of tremendous use due to the fact that more limited research on diagnostic test performance characteristics tends to focus on groups who have a higher cancer incidence.


The results of the research allow for some tentative inferences to be drawn; however, it is important to keep in mind the constraints of the study. A large %age (more than 90 %) of R-PPL EBUS's translations have been successful. The accuracy of the diagnosis was more than 72%. The rate of problems was lower than the standard deviation of minus 2%. The R-EBUS treatment for peripheral pulmomary lesions is an approach that is economical. A future prospective study in the form of a randomised trial comparing the test performance of each technology for a sampling of PPLs compared with a well-defined reference standard is warranted, and it should be compared with other methods such as electromagnetic navigation bronchoscopy. Given the balance with respect to the overall diagnostic superiority of R-EBUS, a future prospective study should compare R-EBUS with other methods such as EMNB (ENB)


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