Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

Search
Advanced Search
OPEN ACCESS
mobile search button mobile menu button

Articles

Page Path
HOME > Cancer Res Treat > Volume 56(2); 2024 > Article
Original Article
Lung and Thoracic cancer Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis
Soo Han Kim1,2orcid, Hyun Sung Chung3, Jinmi Kim2,4, Mi-Hyun Kim1, Min Ki Lee1, Insu Kim5,orcid, Jung Seop Eom1,2,orcid
Cancer Research and Treatment : Official Journal of Korean Cancer Association 2024;56(2):464-483.
DOI: https://doi.org/10.4143/crt.2023.749
Published online: November 29, 2023

1Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea

2Biomedical Research Institute, Pusan National University Hospital, Busan, Korea

3Division of Pulmonology, National Cancer Center, Goyang, Korea

4Department of Biostatistics, Pusan National University Hospital, Busan, Korea

5Department of Internal Medicine, Dong-A University Hospital, Busan, Korea

Correspondence: Insu Kim, Department of Internal Medicine, Dong-A University Hospital, 26 Daesingongwon-ro, Seo-gu, Busan 49201, Korea
Tel: 82-51-240-5597 Fax: 82-51-242-5852 E-mail: wisedoc08@gmail.com
Co-correspondence: Jung Seop Eom, Department of Internal Medicine, Pusan National University School of Medicine/Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea
Tel: 82-51-240-7845 Fax: 82-51-254-3127 E-mail: ejspulm@gmail.com
• Received: June 12, 2023   • Accepted: November 28, 2023

Copyright © 2024 by the Korean Cancer Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 3,365 Views
  • 156 Download
  • 1 Web of Science
  • 1 Scopus
prev next
Full Article

Download PDF Download PDF

  • Purpose
    Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines.
  • Materials and Methods
    We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total lesion number. Subgroup analysis was performed to identify related factors.
  • Results
    Forty-one studies with a total of 13,133 PLLs were included. The pooled diagnostic yield of RP-EBUS was 0.72 (95% confidence interval [CI], 0.70 to 0.75). Significant heterogeneity was observed among studies (χ2=292.38, p < 0.01, I2=86.4%). In a subgroup analysis, there was a significant difference in diagnostic yield based on RP-EBUS findings (within, adjacent to, invisible), with a risk ratio of 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to, 4.20 (95% CI, 1.89 to 9.32) between within and invisible, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible. There was a significant difference in diagnostic yield based on lesion size, histologic diagnosis, computed tomography (CT) bronchus sign, lesion character, and location from the hilum. The overall complication rate of TBB with RP-EBUS was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%).
  • Conclusion
    Our study showed that TBB with RP-EBUS is an accurate diagnostic tool for PLLs with good safety profiles, especially for PLLs with within orientation on RP-EBUS or positive CT bronchus sign.
  • Key words: Bronchoscopy, Lung neoplasms, Meta-analysis, Pulmonary nodule, Radial probe endobronchial ultrasound
The National Lung Cancer Screening Trial (NLST) demonstrated a 20% reduction of mortality in lung cancer by low-dose computed tomography, which led to an increased detection rate of peripheral lung lesions (PLLs) (1.5 million PLLs per 5 million U.S. population annually) [1,2]. However, only 5.2% of PLLs were finally diagnosed with lung cancer, implying that most PLLs were benign [1]. Because most of them are benign, it is necessary to select the target patients who need invasive examination carefully. To this end, positron emission tomography–computed tomography can be considered in the intermediate risk group, and even if biopsy is performed, non-surgical biopsy is recommended [3].
The most common non-surgical procedures to diagnose PLLs are bronchoscopic transbronchial biopsy (TBB) and transthoracic needle biopsy (TTNB) [3,4]. TBB using the conventional bronchoscope showed a suboptimal diagnostic yield for malignancy ranging from 0.34-0.63 in the diagnosis of PLLs [3]. To overcome this issue, radial probe endobronchial ultrasound (RP-EBUS) has been introduced, providing a circumferential ultrasound image of the surrounding lung, confirming the accurate location of PLLs [5]. RP-EBUS with a guide sheath (GS) is a commonly performed TBB procedure enabling access to and detection of PLLs through the bronchoscope’s working channel [6]. After the detection of PLLs by RP-EBUS with GS, RP-EBUS is withdrawn, leaving the GS near PLLs as an extended working channel. Then, biopsy instruments are inserted through GS for tissue acquisition.
Although safe, a previous meta-analysis by Wang Memoli et al. [7] reported that the pooled diagnostic yield of TBB using RP-EBUS for PLLs is 71%, which is lower than that of TTNB (90%). To increase the diagnostic yield of TBB, newer technologies, such as virtual bronchoscopic navigation (VBN) [8], electromagnetic navigation bronchoscopy (ENB) [9], and ultrathin bronchoscopes [10], have been introduced with increasing frequency over the last decade, in addition to previous technology such as fluoroscopy (Flu) [3]. However, there is a lack of systematic research reflecting the current status of TBB performance using RP-EBUS.
Thus, we aimed to evaluate the updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS based on recently published articles in the last 10 years and to generate recommendations for the development of the Korean Association of Lung Cancer guidelines on RP-EBUS. Furthermore, we evaluated the factors affecting the diagnostic yield and associated complications.
1. Literature search
We performed a meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [11]. The study protocol is registered with the PROSPERO database (Identifier: CRD42022378949). We searched MEDLINE and EMBASE (from January 2013 to December 2022) to identify all studies that employed RP-EBUS to evaluate PLLs using a predetermined protocol (Table 1). A manual search of references cited in original and review papers was done for relevant studies, which might have been missed by the electronic search.
2. Selection of studies
All articles identified by the search strategy were independently assessed by four authors (S.H.K., H.S.C., I.K., and J.S.E.). Discordance was resolved by consensus. Abstracts were initially examined, and studies were selected for inclusion only after all reviewers assessed the full-text articles. Criteria for inclusion were as follows: (1) RP-EBUS for diagnosis of PLL providing a diagnostic yield, (2) diagnosis confirmed histologically or by close clinical follow-up, and (3) studies where at least 50 patients were enrolled.
We excluded review articles, meta-analysis articles, letters, case reports with fewer than 50 patients, articles not available in English, articles focusing on modalities other than RP-EBUS, or articles only limited to PLLs with a narrow spectrum (e.g., malignant lesion, ground-glass opacity lesion [GGO]). Furthermore, articles focusing on cone-beam computed tomography (CT) or robotic bronchoscopy were also excluded due to the high risk of selection bias. When two or more studies were published by the same author(s), the methods sections were reviewed to check for overlapping study periods. If so, we included only one publication with the greatest number of patients to prevent duplication of the study cohorts.
3. Data extraction
All data were independently extracted by S.H.K., H.S.C., and I.K., followed by a comparison of extracted data. Disagreements were resolved by further discussion with the other investigator (J.S.E.). The following were retrieved: author, year of publication, study design (randomized controlled trial, prospective, retrospective, or unknown), total number of lesions, number of successful diagnoses, type of bronchoscope (standard bronchoscope, thin bronchoscope, ultrathin bronchoscope), use of guidance modalities (e.g., GS, VBN, Flu, ENB), biopsy methods (e.g., forceps biopsy, cryobiopsy), mean lesion size, prevalence of malignancy, RP-EBUS findings, histologic diagnosis, presence of CT bronchus sign, lesion character (solid, part-solid, GGO), distance from the hilum (central, inner third; intermediate, middle third; peripheral, outer third in the lung field on CT scan) [12], complications, and reference standard.
The quality of selected studies was evaluated by S.H.K., H.S.C., and I.K., using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool [13]. This validated tool contains 14 signaling questions to evaluate four main components (patient selection, index test, reference standard, and flow and timing) in two categories (risk of bias and applicability concerns). Disagreements were resolved by further discussion with the other investigator (J.S.E.).
4. Statistical analysis
Meta-analysis was performed using the meta package of R statistical software (ver. 4.0.5, http://www.R-project.org). A p-value of < 0.05 was considered statistically significant. The primary outcome was the diagnostic yield with a 95% confidence interval (CI), calculated by dividing the number of successful diagnoses by the total number of lesions. Inverse variance weighting across selected studies was applied to evaluate the pooled diagnostic yield, where the weight of each study was based on the number of lesions.
Subgroup analysis was performed to identify the factors associated with diagnostic yield. Stratified analysis on diagnostic yield was based on lesion size (≤ 20 mm vs. > 20 mm), histologic diagnosis (malignant vs. benign), RP-EBUS findings (within vs. adjacent to vs. invisible), CT bronchus sign (present vs. absent), lesion character (solid vs. partsolid vs. GGO), and distance from the hilum (peripheral vs. non-peripheral [central and/or intermediate]). In addition, subgroup analysis based on adjunctive modalities (ENB, GS, Flu, VBN), bronchoscope types (standard, thin, ultrathin bronchoscope), and use of cryobiopsy were evaluated. A subgroup meta-analysis was performed using the Mantel-Haenszel risk ratio (RR) [14,15]. RR > 1 was in favor of the former variable for the diagnostic yield, while RR < 1 was in favor of the latter variable.
Study heterogeneity was assessed using the Cochran Q test (χ2 test) and quantified by the I2 index [16]. Statistical heterogeneity was indicated in cases of p < 0.01 in the χ2 test [16], and I2 index values of > 50% indicated significant heterogeneity [17]. Random-effect models with the inverse variance method were applied to reflect the variability of effect sizes among included studies with diversity in adjunctive modalities [18]. Publication bias was evaluated using funnel plot asymmetry [19] based on the Egger and Begg tests [20,21]. We used funnel plots of standard error or diagnostic yield (logit transformed).
1. Literature search and study selection
After removing duplicates, the search algorithm revealed 2,422 potentially relevant papers (Fig. 1). Following the abstract review, 115 articles were selected for full-text review. Of these, 75 articles were excluded according to the exclusion criteria, and one study missed in the database search was added [22]. Therefore, 41 studies formed the basis of our systematic review [22-62].
2. Study description
A total of 13,133 PLLs were included. Table 2 lists the study characteristics and summarizes their features [22-62]. Overall, 13 studies were randomized controlled trials, seven were prospective, and 21 were retrospective studies. The prevalence of malignancy was reported in 35 studies (median, 78%; interquartile range, 68 to 83). Among them, 15 studies showed a prevalence of malignancy ≤ 75%, whereas 20 studies showed > 75%. There was variation in additional guidance devices used among included studies, such as GS (31 studies), Flu (26 studies), VBN (16 studies), ultrathin bronchoscopy (5 studies), and ENB (1 study). S1 Table provides a quality assessment of all included studies based on QUADAS-2. The overall analysis showed good performance in the patient selection and index test criteria. However, it showed poor performance in the reference standard in addition to flow and timing criteria, which indicates the potential for significant bias. The funnel plot (Fig. 2) was not asymmetric, with both Egger’s (p=0.156) and Begg’s tests (p=0.103) showing insignificant p-values, indicating the absence of publication bias.
3. Test performance: meta-analysis
The inverse variance weighted overall diagnostic yield was 0.72 (95% CI, 0.70 to 0.75) (Fig. 3) [22-62]. The diagnostic yield among studies ranged from 0.49 to 0.94. The χ2 value of 293.38 (p < 0.01) and I² index of 86.4% indicated substantial heterogeneity across studies. The pooled sensitivity and specificity for malignant PLLs in 30 studies were 0.76 (95% CI, 0.72 to 0.79) and 0.98 (95% CI, 0.96 to 0.99), respectively [22-25,29,31-35,37-46,48,49,51,55-57,59-62].
The factors related to diagnostic yield were further evaluated by subgroup meta-analysis. Regarding trichotomous variables (Table 3), there were significant differences in the pooled diagnostic yield based on RP-EBUS findings, where RR was 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to in 12 studies, 4.20 (95% CI, 1.89 to 9.32) between within and invisible in five studies, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible in five studies (Fig. 4A-C) [28,31,38,42,45-47,52,53,55,61,62]. As for lesion characters (Table 3), there was a significant difference in the pooled diagnostic yield between solid and part-solid, where RR was 1.15 (95% CI, 1.03 to 1.28) in seven studies. However, there was a difference in the pooled diagnostic yield without significance in the other variables, where RR was 1.40 (95% CI, 0.93 to 2.11) between solid and GGO in three studies, and 1.39 (95% CI, 0.93 to 2.11) between part-solid and GGO in two studies (S2A-S2C Fig.) [22,34,42,53,55,56,60,61].
Regarding dichotomous variables (Table 3), the pooled diagnostic yield was significantly different based on lesion size in 21 studies (≤ 20 vs. > 20 mm: RR, 0.78; 95% CI, 0.73 to 0.83) (S3A Fig.) [22,24,26,27,31-35,37,41,42,45,46,48,53,55,59-62], histologic diagnosis in 30 studies (malignancy vs. benign: RR, 1.30; 95% CI, 1.12 to 1.52) (S3B Fig.) [22-25,29,31-35,37-46,48,49,51,55-57,59-62], CT bronchus sign in 14 studies (present vs. absent: RR, 1.683; 95% CI, 1.32 to 2.14) (S3C Fig.) [22,27,28,30,33-35,40,45,53,56,60-62], and distance from the hilum in 11 studies (peripheral vs. non-peripheral: RR, 0.90; 95% CI, 0.84 to 0.96) (S3D Fig.) [22,30,35,37,40,45,55,56,60-62].
4. Test performance based on technologies
Regarding frequently used adjunctive modalities (Table 4), Flu+GS was the most commonly used combination during TBB using RP-EBUS (13 studies) [25,29-32,37,39,42,44,47,50,51,58], followed by Flu+GS+VBN (10 studies) [22,24,30,35,40,54,56,57,60,62], GS only (seven studies) [26,27,34,43,46,49,53], and no adjunctive modalities (six studies) [23,28,33,41,45,52]. The pooled diagnostic yields of adjunctive modalities were 0.73 (95% CI, 0.67 to 0.79) for Flu+GS+VBN, 0.73 (95% CI, 0.67 to 0.78) for Flu+GS, 0.72 (95% CI, 0.68 to 0.76) for GS only, and 0.70 (95% CI, 0.62 to 0.76) for no adjunctive modalities (p=0.903) (S4 Fig.). Regarding a single adjunctive modality, the pooled diagnostic yield was higher without statistical significance for GS (0.72; 95% CI, 0.69 to 0.75) compared with non-GS (0.70; 95% CI, 0.62 to 0.78) (p=0.658), VBN (0.74; 95% CI, 0.69 to 0.79) compared with non-VBN (0.71; 95% CI, 0.68 to 0.74) (p=0.356), but not for Flu (0.73; 95% CI, 0.69 to 0.77) compared with non-Flu (0.73; 95% CI, 0.69 to 0.76) (p=0.929) (S5A-S5D Fig.). Regarding bronchoscope type, the pooled diagnostic yields of thin (22 studies) [22,24,30,34,35,37-42,44-46,48,50,53,57,58,60-62], standard (12 studies) [23,27-29,32,33,36,44,50,52,54,59], and ultrathin (four studies) [22,35,55,57] bronchoscopes were 0.73 (95% CI, 0.68 to 0.78), 0.71 (95% CI, 0.66 to 0.75), and 0.73 (95% CI, 0.69 to 0.77), respectively (p=0.715) (S6 Fig.). Regarding the biopsy method, the pooled diagnostic yield of cryobiopsy (six studies) [47,52,54,57,59,61] was 0.78 (95% CI, 0.70 to 0.85) (one study, not evaluable due to insufficient data) [60].
5. Complication rates
Complication rates were 6.8% (726 out of 10,700 lesions) across 34 studies [22,23,26-36,39-43,45-49,51-55,57-62], whereas seven studies [24,25,37,38,44,50,56] did not report complication rates (Table 2). Among 34 studies, no complication was noted in one study [55]. The most common complication was bleeding, with a pooled rate of 4.5% (482 out of 10,700). The pooled rate of pneumothorax was 1.4% (148 out of 10,700), whereas that of chest tube insertion was 0.3% (33 out of 10,700). The pooled infection rate (including pneumonia) was 0.4% (45 out of 10,700). There were two cases of lifethreatening complications without death (one myocardial infarction and one severe bleeding). No death was reported in any study.
To our knowledge, this is the first updated meta-analysis investigating the performance of RP-EBUS for diagnosing PLLs, including 13,133 PLLs from recent publications in 10 years. Our study showed the overall diagnostic yield of RP-EBUS as 0.72. Moreover, subgroup analysis showed that lesion size, histologic diagnosis, RP-EBUS findings, CT bronchus sign, lesion character, and distance from the hilum were associated with the performance of TBB using RP-EBUS. Lastly, our study showed a good safety profile during TBB using RP-EBUS, where the overall complication rate was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%).
RP-EBUS finding was previously reported as an important factor for the diagnostic yield, which correlates with our study results. Tay et al. [25] reported that visualized PLLs on RP-EBUS were associated with significantly higher diagnostic yield than invisible PLLs on RP-EBUS (0.66 vs. 0.20; p=0.001). Among visualized PLLs on RP-EBUS, Ali et al. [63] reported significantly higher diagnostic yield in within oriented lesions compared to that of adjacently oriented lesions on RP-EBUS (0.79 vs. 0.52; p < 0.001). In line with this, the presence of CT bronchus sign was also known to be associated with the diagnostic yield, which correlates with our study finding. The same group also reported significantly higher diagnostic yield in PLLs with bronchus sign compared to that of PLLs without bronchus sign on CT (0.77 vs. 0.52, p=0.008) [63]. This might be attributed to the fact that the presence of CT bronchus sign is significantly associated with the visualization of the lesion on RP-EBUS (odds ratio [OR], 31.1; p < 0.001) and within the orientation of RP-EBUS to the lesion (OR, 44.8; p < 0.001) [27]. Therefore, TBB with RP-EBUS is highly recommended in within oriented or CT bronchus sign present PLLs.
Our study also showed that smaller size (≤ 2 cm), benign, and peripheral location were associated with significantly lower diagnostic yield during TBB using RP-EBUS. A previous meta-analysis showed that the diagnostic yield of PLLs ≤ 2 cm and > 2 cm were 0.61 and 0.76, respectively (p < 0.001) [63]. This might be attributed to lower visualization of PLLs ≤ 2 cm compared to PLLs > 2 cm on RP-EBUS (0.49 vs. 0.90, p < 0.001) [64]. Furthermore, the previous meta-analysis also showed that the diagnostic yields of malignant PLLs and benign PLLs were 0.72 and 0.60, respectively (p=0.018) [63]. This might be associated with a higher visualization rate in malignant PLLs compared to benign PLLs on RP-EBUS (0.85 vs. 0.66, p=0.025), which could be attributed to distinct features of bronchial invasion and airway distortion in malignant PLLs compared to ill-defined borders with subtle changes in benign PLLs, such as inflammation [25,32]. Lastly, Huang et al. [64] showed that the diagnostic yield of peripheral and central PLLs were 0.50 and 0.94, respectively (p < 0.001), which might be attributed to differences in accessibility regarding RP-EBUS scanning and sampling. Therefore, to improve the diagnostic yield in PLLs with the above factors, our study highlights the need for newer technologies in the field of bronchoscopic TBB.
Regarding subgroup analysis of the frequently used adjunctive modalities, our study showed that the diagnostic yield of RP-EBUS with GS (0.72) was slightly higher than that of RP-EBUS alone (0.70), as well as that of the GS group (0.72) compared with that of the non-GS group (0.70). GS enables accurate, repeated sampling at the same lesion after fixation at PLLs, and also prevents excessive bleeding by wedging GS after TBB [6]. In a recent study by Oki et al. [60], GS showed significantly higher diagnostic yield compared to non-GS (0.55 vs. 0.74, p=0.033), where interaction was especially evident based on lobar locations for GS (upper, 0.63 vs. lower, 0.46; p=0.004) and non-GS (upper, 0.43 vs. others, 0.50; p=0.197) (p-interaction=0.003). However, due to the small diameter of GS (SG-200C; Olympus; external diameter, 1.95 mm) for thin bronchoscopes, the use of biopsy tools for larger samples such as standard forceps (1.8 or 1.9 mm) is limited. This can be overcome by additional TBB by the non-GS method following the GS method, which is beneficial, especially in part-solid or GGO nodules [37,50]. Furthermore, there is a technical issue such as kinking of GS, which interrupts the introduction of biopsy tools, which can be overcome by parallel alignment of the bronchoscope to GS and advancement of the bronchoscope to PLLs as close as possible [42].
For the diagnosis of PLLs, transthoracic needle aspiration/biopsy (TTNA/B) is another alternative method that shows a high diagnostic yield (> 90%) [4]. However, it is associated with a higher risk of complications, especially pneumothorax (any pneumothorax, 15%; pneumothorax requiring a chest tube, 6.6%) [4]. Therefore, TTNA/B could be recommended for PLLs, especially those with pleural contact, but should be performed with caution considering the high complication rates, especially in patients with chronic obstructive pulmonary disease, pleural effusion, and interstitial lung disease [4]. The diagnostic yield of TBB with RP-EBUS may be relatively low, but recent advances in the field of bronchoscopy have improved it. Ultrathin bronchoscopy showed improved RP-EBUS positioning for PLLs, as well as an improved diagnostic yield of PLLs, even in peripheral locations from the hilum and upper lobes with an acute angle [15]. In a recent meta-analysis by Folch et al. [65] on ENB, RP-EBUS combined with ENB showed a pooled sensitivity of 0.80 (95% CI, 0.74 to 0.83) in PLLs suspected of lung cancer, which was higher than that with ENB alone (0.72; 95% CI, 0.66 to 0.76). Cryobiopsy is characterized by large tissue samples with good quality, which is associated with improved diagnostic yield, even in PLLs ≤ 2 cm and adjacent to findings on RP-EBUS [66,67]. Thus, TBB could be a reasonable modality in patients, especially those with a positive bronchus sign and a high risk of complications during TTNA/B.
Although our study includes recent publications from the past 10 years, we reported the diagnostic yield of PLLs as 0.72, which does not appear to be significantly different from the 0.71 reported in the subgroup analysis of RP-EBUS in a previous meta-analysis [7]. Possible explanations are as follows. First, our study included a higher proportion of studies with a low risk of bias (n=16/41, 0.39) compared to the previous meta-analysis (n=5/19 [one study not reported], 0.26) [7]. Studies with a lower risk of bias are known to be associated with a significantly lower diagnostic yield compared to those with a high risk of bias (0.66 vs. 0.71, p=0.018) [68]. Thus, the diagnostic yield in the previous meta-analysis might have been overestimated, thereby hampering the accurate evaluation of the diagnostic yield of RP-EBUS between the recent and past publications. Second, the included studies evaluating new modalities, such as cryobiopsy (seven studies), ENB (one study), and ultrathin bronchoscope (five studies), were relatively limited in number. A relatively small number of included studies on these factors might have led to the underestimation of the accurate diagnostic yield of PLLs.
Our study has some limitations. First, the quality of the included studies was inconsistent, which might be attributed to different designs, patient selection, and reference standards, including the radiological follow-up period. This might have led to heterogeneity in the diagnostic yield among the included studies. Second, the number of studies on GGO of lesion character was also relatively low, which could hamper accurate evaluation of overall diagnostic yield and RR compared with other variables of lesion character. Third, our study excluded articles not available in English, systematic reviews, and conference abstracts due to the possibility of low study quality. However, this could have an influence on publication bias. Fourth, our study could not collect data on the grade of bleeding due to the heterogeneity of the included studies, which limited analysis of clinically meaningful bleeding.
In conclusion, our study showed that TBB with RP-EBUS is an accurate diagnostic tool for diagnosing PLLs with good safety profiles, especially in PLLs with within orientation on RP-EBUS or the CT bronchus sign.
Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).
crt-2023-749_S1_Table.pdf
crt-2023-749_S2_Fig.pdf
crt-2023-749_S3_Fig.pdf
crt-2023-749_S4_Fig.pdf
crt-2023-749_S5_Fig.pdf
crt-2023-749_S6_Fig.pdf

Ethical Statement

An ethics statement is not applicable because this study is based exclusively on the published literature.

Author Contributions

Conceived and designed the analysis: Eom JS.

Collected the data: Kim SH, Chung HS, Kim I, Eom JS.

Contributed data or analysis tools: Kim SH, Kim J, Kim MH, Lee MK, Kim I, Eom JS.

Performed the analysis: Kim SH, Kim J, Kim MH, Lee MK, Kim I, Eom JS.

Wrote the paper: Kim SH, Eom JS.

Conflicts of Interest

Conflict of interest relevant to this article was not reported.

Acknowledgements
This work was supported by a clinical research grant from Pusan National University Hospital in 2024, the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (NRF-2022R1F1A1074117), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR20C0026).
Fig. 1.
Flow diagram of search and study selection.
crt-2023-749f1.jpg
Fig. 2.
Funnel plot of publication bias.
crt-2023-749f2.jpg
Fig. 3.
Overall diagnostic yield of radial probe endobronchial ultrasound. CI, confidence interval; IV, inverse variance [22-62].
crt-2023-749f3.jpg
Fig. 4.
Diagnostic yield of radial probe endobronchial ultrasound based on sonographic findings [28,31,38,42,45-47,52,53,55,61,62]. (A) Within vs. adjacent to. (B) Within vs. invisible. (C) Adjacent to vs. invisible. CI, confidence interval.
crt-2023-749f4.jpg
Table 1.
Search strategy for meta-analysis
Search strategy
1 “Endobronchial ultrasound AND lung AND nodule(s)”
2 “Endobronchial ultrasound AND lung AND lesion(s)”
3 “Endobronchial ultrasound AND lung AND cancer(s)”
4 “Endobronchial ultrasound AND pulmonary AND nodule(s)”
5 “Endobronchial ultrasound AND pulmonary AND lesion(s)”
6 “Endobronchial ultrasound AND pulmonary AND cancer(s)”
7 “Endobronchial ultrasound AND peripheral AND nodule(s)”
8 “Endobronchial ultrasound AND peripheral AND lesion(s)”
9 “Endobronchial ultrasound AND peripheral AND cancer(s)”
10 “Endobronchial ultrasonograph(y) AND lung AND nodule(s)”
11 “Endobronchial ultrasonograph(y) AND lung AND lesion(s)”
12 “Endobronchial ultrasonograph(y) AND lung AND cancer(s)”
13 “Endobronchial ultrasonograph(y) AND pulmonary AND nodule(s)”
14 “Endobronchial ultrasonograph(y) AND pulmonary AND lesion(s)”
15 “Endobronchial ultrasonograph(y) AND pulmonary AND cancer(s)”
16 “Endobronchial ultrasonograph(y) AND peripheral AND nodule(s)”
17 “Endobronchial ultrasonograph(y) AND peripheral AND lesion(s)”
18 “Endobronchial ultrasonograph(y) AND peripheral AND cancer(s)”
19 “Radial probe AND lung AND nodule(s)”
20 “Radial probe AND lung AND lesion(s)”
21 “Radial probe AND lung AND cancer(s)”
22 “Radial probe AND pulmonary AND nodule(s)”
23 “Radial probe AND pulmonary AND lesion(s)”
24 “Radial probe AND pulmonary AND cancer(s)”
25 “Radial probe AND peripheral AND nodule(s)”
26 “Radial probe AND peripheral AND lesion(s)”
27 “Radial probe AND peripheral AND cancer(s)”
Table 2.
Study characteristics
No. Author/year Study design Selection criteria No. of lesions Diagnostic yield Prevalence of malignancy (%) Additional guidance Biopsy method Bronchoscope Complications Reference/Comparison test
1 Fuso 2013 [23] Retrospective PLL not visible on routine bronchoscopy 447 0.77 80.3 None Forceps Standard 2 Bleed, 8 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
2 Tamiya 2013 [24] Prospective PLL ≤ 30 mm 68 0.78 63.2 GS, Flu, VBN Brush, forceps, needle Thin NE Histology by alternative means or clinical/radiologic surveillance (6 mo)
3 Tay 2013 [25] Retrospective PLL not visible on routine bronchoscopy 196 0.56 68.9 GS, Flu Brush, forceps NE NE Histology by alternative means or clinical/radiologic surveillance
4 Chen 2014 [26] Retrospective NE 467 0.69 NE GS Brush, forceps, needle NE 6 Bleed, 13 PNX (7 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance
5 Evison 2014 [27] Retrospective PLL not visible on routine bronchoscopy 117 0.69 82.9 GS Forceps Standard 6 Bleed 1 PNX (1 requiring chest tube), 2 poor tolerance to bronchoscope Clinical/radiologic surveillance (6 mo)
6 Kuo 2014 [28] Retrospective PLL without endobronchial lesion, extrinsic compression, submucosal infiltration, or orifice narrowing 271 0.76 90.0 None Brush, forceps Standard 22 Bleed, 7 PNX NE
7 Sanchez-Font 2014 [29] RCT PLL not visible on routine bronchoscopy 50 0.78 90.0 GS, Flu Brush, forceps Standard 9 Bleed Histology by alternative means or clinical/radiologic surveillance (6 mo)
8 Asano 2015 [30] Retrospective PLL ≤ 30 mm 194 0.74 NE GS, Flu, VBN Brush, forceps Thin 1 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (24 mo)
9 Boonsarngsuk 2015 [31] Prospective PLL with feeding bronchi, but not visible on routine bronchoscopy 112 0.80 67.9 GS, Flu Brush, forceps Standard 1 PNA Histology by alternative means or clinical/radiologic surveillance
10 Chan 2015 [32] Retrospective Exclusion: PLL < 1 cm, endobronchial lesions, airway narrowing, pure GGO, absence of CT bronchus sign, presence of a submucosal lesion 120 0.69 63.3 GS, Flu Forceps Standard 7 Bleed, 1 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
11 Guvenc 2015 [33] Retrospective Exclusion: bronchopneumonia, solid lesions < 10 mm, glass opacity (pure or part-solid less than 50%) lesions, solid lesions < 15 mm touching the visceral pleura 760 0.62 73.0 None Forceps Standard 9 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (6 mo)
12 Minezawa 2015 [34] Retrospective PLL ≤ 30 mm 149 0.73 73.8 GS Brush, forceps Thin 1 Delirium, 4 PNA, 5 PNX Clinical/radiologic surveillance (12 mo)
13 Oki 2015 [35] RCT PLL ≤ 30 mm 305 0.67 76.1 GS, Flu, VBN Forceps Thin, ultrathin 2 Bleed, 1 PNA, 8 PNX (3 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (12 mo)
14 Jacomelli 2016 [36] Retrospective Pulmonary nodule or mass (non-diagnostic by routine bronchoscopy) 51 0.67 NE Flu Brush, forceps, needle Standard 5 Bleed, 2 PNX (2 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (6 mo)
Exclusion: PLL with endobronchial lesions or lost to follow-up
15 Kunimasa 2016 [37] Retrospective NE 88 0.82 97.7 GS, Flu Brush, forceps Thin NE Histology by alternative means or clinical/radiologic surveillance
16 Steinfort 2016 [38] Prospective NE 245 0.58 82.4 ENB, GS, Flu, VBN Brush, forceps Thin NE Histology by alternative means or clinical/radiologic surveillance (12 mo)
17 Wang 2016 [39] Prospective PLL in the outer 1/3 pulmonary field, invisible under routine bronchoscopy 54 0.82 87.0 GS, Flu Brush, forceps Thin 1 Bleed Histology by alternative means or clinical/radiologic surveillance
18 Asano 2017 [40] RCT PLL > 30 mm 129 0.81 93.8 GS, Flu, VBN Brush, forceps Thin 2 Bleed, 1 hyperventilation, 1 PNA Histology by alternative means or clinical/radiologic surveillance (24 mo)
Exclusion: endobronchial lesion, GGO lesion
19 Huang 2017 [41] Retrospective PLL ≥ 8 mm, not visible on routine bronchoscopy 2,144 0.72 77.9 None Brush, forceps Thin 10 Bleed, 38 PNX Histology by alternative means or clinical/radiologic surveillance
20 Eom 2018 [42] Retrospective NE 200 0.73 77.5 GS, Flu Brush, forceps Thin, 1 PNA, 2 PNX NE
21 Good 2018 [43] Retrospective NE 68 0.56 75.0 GS Brush, forceps, needle NE 1 Dislodgement of GS, 3 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
22 Tanner 2018 [44] RCT PLL 15-50 mm 112 0.49 75.0 GS, Flu Brush, forceps Standard, thin NE Histology by alternative means or clinical/radiologic surveillance (12 mo)
23 Zhang 2018 [45] Retrospective Exclusion: Bronchial lesions on routine bronchoscopy, EBUS-GS TBB, malignant lesions without postoperative pathology, follow-up loss, or final diagnosis unknown 328 0.55 58.8 None Brush, forceps Thin 13 Bleed, 3 chest pain Histology by alternative means or clinical/radiologic surveillance
24 Bo 2019 [46] RCT PLL with a high likelihood of malignancy, 8-30 mm 670 0.73 51.3 GS, VBN Forceps Thin 7 Bleed, 12 PNX (4 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (24 mo)
25 Kho 2019 [47] Retrospective Exclusion: endobronchial lesion, incomplete clinical data, not visualized by RP-EBUS 114 0.68 NE GS, Flu Forceps, cryoprobe NE 24 Bleed, 1 PNX Histology by alternative means or clinical/radiologic surveillance
26 Oki 2019 [22] RCT PLL ≤ 30 mm 356 0.64 79.2 GS, Flu, VBN Forceps, needle Thin, ultrathin 3 Bleed, 1 myocardial infarction, 1 nausea, 4 PNX (1 requiring chest tube), 1 vomiting Histology by alternative means or clinical/radiologic surveillance (12 mo)
27 Xu 2019 [48] RCT PLL 8-30 mm 115 0.84 65.2 VBN Forceps Thin 1 Bleed, 1 PNX Histology by alternative means or clinical/radiologic surveillance (6 mo)
28 Zhu 2019 [49] Retrospective NE 239 0.78 52.3 GS Forceps NE 21 Bleed, 2 chest pain, 18 fever, 2 PNA, 1 PNX, Histology by alternative means or clinical/radiologic surveillance
29 Boonsarngsuk 2020 [50] Prospective PLL with feeding bronchi 90 0.82 77.8 GS, Flu Brush, forceps Thin NE Histology by alternative means or clinical/radiologic surveillance
Exclusion: PLL < 10 mm, no feeding bronchi
30 Samaranayake 2020 [51] RCT Exclusion: PLL < 15 mm, lack of bronchus sign, less than 180-degree view of the lesion on ultrasound, previous RP-EBUS TBB within 2 wk 54 0.78 81.5 GS, Flu Brush, forceps NE 7 Bleed Histology by alternative means or clinical/radiologic surveillance
31 Goel 2021 [52] Retrospective NE 126 0.79 50.0 None Cryoprobe Standard 126 Bleed, 4 respiratory failure not requiring escalation of care NE
32 Hong 2021 [53] Retrospective NE 607 0.76 61.4 GS Brush, forceps Thin 12 PNX (3 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (12 mo)
33 Jiang 2021 [54] Prospective PLL 10-50 mm, solid or part-solid nodule, bronchus sign pulmonary nodule 59 0.70 NE GS, Flu, VBN Brush, cryoprobe, forceps Standard 8 Bleed, 2 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (6 mo)
Exclusion: endobronchial lesion, atelectasis, or obstructive
34 Zheng 2021 [55] RCT PLL with the presence of the bronchus sign 120 0.78 83.3 Flu, VBN Brush, forceps Ultrathin None Histology by alternative means or clinical/radiologic surveillance (12 mo)
Exclusion: endobronchial lesion, atelectasis, or obstructive pneumonia
35 Ito 2022 [56] RCT PLL with no endobronchial lesion 1,634 0.70 84.8 GS, Flu, VBN Brush, forceps, needle NE NE Histology by alternative means or clinical/radiologic surveillance (24 mo)
36 Kim 2023 [57] Retrospective PLL ≤ 30 mm 110 0.79 83.6 GS, Flu, VBN Brush, cryoprobe, forceps, needle Standard, thin, ultrathin 9 Bleed, 1 PNA, 1 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
37 Lee 2022 [58] Retrospective NE 954 0.75 NE GS, Flu Brush, forceps Thin 3 Bleed, 5 PNA, 2 PNX NE
38 Liu 2022 [59] RCT PLL ≤ 30 mm, with the bronchial sign 138 0.74 69.6 GS, VBN Forceps, cryoprobe Standard 133 Bleed, 5 PNX Histology by alternative means or clinical/radiologic surveillance (6 mo)
Exclusion: endobronchial lesion
39 Oki 2022 [60] RCT PLL ≤ 30 mm 596 0.64 78.5 GS, Flu, VBN Brush, cryoprobe, forceps, needle Thin, ultrathin 1 Arrhythmia, 4 bleed (1 significant bleeding), 1 broken GS, 7 PNA, 8 PNX (4 requiring chest tube), 2 transient hypoxemia Histology by alternative means or clinical/radiologic surveillance (12 mo)
40 Tanaka 2022 [61] Prospective PLL < 30 mm, located beyond the subsegmental bronchi 50 0.94 94.0 Flu, VBN Cryoprobe Thin 46 Bleed, 1 PNA, 1 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance
41 Zheng 2023 [62] RCT PLL ≥ 8 mm 426 0.84 80.8 GS, Flu, VBN Forceps, needle Thin 7 Bleed Histology by alternative means or clinical/radiologic surveillance (12 mo)
Exclusion: absence of the bronchus sign, pure GGO, endobronchial lesion

CT, computed tomography; EBUS-GS, endbronchial ultrasound guide sheath; ENB, electromagnetic navigation bronchoscopy; Flu, fluoroscopy; GGO, ground glass opacity; GS, guide sheath; NE, not evaluable; PLL, peripheral lung lesion; PNA, pneumonia; PNX, pneumothorax; RCT, randomized controlled trial; RP-EBUS, radial probe endobronchial ultrasound; TBB, transbronchial biopsy; VBN, virtual bronchoscopic navigation.

Table 3.
Stratified meta-analysis for clinical factors
Variable No. of studies No. of lesions Pooled diagnostic yield (95% CI) Risk ratio (95% CI) Heterogeneity
 Overall effect
χ2 I2 (%) p-value z p-value
RP-EBUS findings (1 vs. 2, 1 vs. 3, 2 vs. 3) 12 1.45 (1.23-1.72) 47.3 77 < 0.001 4.37 < 0.001
5 4.20 (1.89–9.32) 16.23 75 0.003 3.52 < 0.001
5 2.59 (1.32-5.01) 12.60 68 0.013 2.75 0.006
 Within (1) 12 2,225 0.83 (0.80-0.86)
 Adjacent to (2) 12 670 0.57 (0.46-0.67)
 Invisible (3) 5 243 0.18 (0.06-0.43)
Lesion characters (1 vs. 2, 1 vs. 3, 2 vs. 3) 7 1.15 (1.03-1.28) 11.04 46 0.087 2.59 0.010
3 1.40 (0.93-2.11) 3.26 39 0.196 1.559 0.112
2 1.39 (0.87-2.22) 0.67 0 0.414 1.39 0.166
 Solid (1) 8 2,894 0.73 (0.65-0.79)
 Part-solid (2) 7 597 0.58 (0.53-0.62)
 GGO (3) 3 46 0.52 (0.33-0.70)
Lesion size (mm) 0.78 (0.73-0.83) 51.3 61 < 0.001 –7.49 < 0.001
 ≤ 20 21 2,380 0.58 (0.52-0.63)
 > 20 21 5,392 0.77 (0.73-0.80)
Histologic diagnosis 1.30 (1.12-1.52) 473.4 94 < 0.001 3.33 < 0.001
 Malignancy 30 7,644 0.76 (0.72-0.79)
 Benign 30 2,320 0.57 (0.48-0.66)
Bronchus sign 1.68 (1.32-2.14) 236.2 94 < 0.001 4.24 < 0.001
 Present 14 4,556 0.77 (0.72-0.82)
 Absent 14 1,231 0.44 (0.33-0.56)
Distance from hilum 0.90 (0.84-0.96) 17.8 44 0.058 –3.38 < 0.001
 Peripheral 11 2,518 0.69 (0.61-0.76)
 Central and/or intermediate 11 1,360 0.76 (0.71-0.80)

CI, confidence interval; GGO, ground glass opacity; RP-EBUS, radial probe endobronchial ultrasound.

Table 4.
Stratified meta-analysis for technologies
No. of studies No. of lesions Pooled diagnostic yield (95% CI) Heterogeneity
 Overall effect
χ2 I2 (%) p-value χ2 p-value
Combined adjunctive modalities 247.53 86 < 0.001 0.57 0.903
 Flu+GS 13 2,194 0.73 (0.67-0.78)
 Flu+GS+VBN 10 3,274 0.73 (0.67-0.79)
 GS 7 1,799 0.72 (0.68-0.76)
 None 6 4,076 0.70 (0.62-0.76)
Single adjunctive modality
 GS 380.46 89 < 0.001 0.20 0.658
  Yes 31 8,196 0.72 (0.69-0.75)
  No 12 4,693 0.70 (0.62-0.78)
 Flu 377.65 89 < 0.001 0.01 0.929
  Yes 26 6,215 0.73 (0.69-0.77)
  No 17 6,674 0.73 (0.69-0.76)
 VBN 381.04 89 < 0.001 0.85 0.356
  Yes 16 4,724 0.74 (0.69-0.79)
  No 27 8,165 0.71 (0.68-0.74)
Bronchoscopes 383.28 90 < 0.001 0.67 0.715
 Standard 12 2,363 0.71 (0.66-0.75) 66.69 84 < 0.001
 Thin 22 7,648 0.73 (0.68-0.78) 310.39 93 < 0.001
 Ultrathin 4 462 0.73 (0.69-0.77) 2.06 0 0.559
Biopsy method
 Cryobiopsy 6 419 0.78 (0.70-0.85) 14.69 66 0.012

CI, confidence interval; Flu, fluoroscopy; GS, guide sheath; VBN, virtual bronchoscopic navigation.

  • 1. Gould MK, Tang T, Liu IL, Lee J, Zheng C, Danforth KN, et al. Recent trends in the identification of incidental pulmonary nodules. Am J Respir Crit Care Med. 2015;192:1208–14. ArticlePubMed
  • 2. National Lung Screening Trial Research Team; Church TR, Black WC, Aberle DR, Berg CD, Clingan KL, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368:1980–91. ArticlePubMedPMC
  • 3. Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e93S–120S. PubMedPMC
  • 4. Kim SH, Kim MH, Lee MK, Eom JS. Problems in the pathologic diagnosis of suspected lung cancer. Tuberc Respir Dis (Seoul). 2023;86:176–82. ArticlePubMedPMCPDF
  • 5. Herth FJ, Ernst A, Becker HD. Endobronchial ultrasound-guided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions. Eur Respir J. 2002;20:972–4. ArticlePubMed
  • 6. Kurimoto N, Miyazawa T, Okimasa S, Maeda A, Oiwa H, Miyazu Y, et al. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. Chest. 2004;126:959–65. ArticlePubMed
  • 7. Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142:385–93. ArticlePubMedPMC
  • 8. Asano F, Matsuno Y, Shinagawa N, Yamazaki K, Suzuki T, Ishida T, et al. A virtual bronchoscopic navigation system for pulmonary peripheral lesions. Chest. 2006;130:559–66. ArticlePubMed
  • 9. Eberhardt R, Anantham D, Herth F, Feller-Kopman D, Ernst A. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest. 2007;131:1800–5. ArticlePubMed
  • 10. Oki M, Saka H. Diagnostic value of ultrathin bronchoscopy in peripheral pulmonary lesions: a narrative review. J Thorac Dis. 2020;12:7675–82. ArticlePubMedPMC
  • 11. McInnes MD, Moher D, Thombs BD, McGrath TA, Bossuyt PM; PRISMA-DTA Group; et al. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement. JAMA. 2018;319:388–96. ArticlePubMed
  • 12. Baaklini WA, Reinoso MA, Gorin AB, Sharafkaneh A, Manian P. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000;117:1049–54. ArticlePubMed
  • 13. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36. ArticlePubMed
  • 14. Ali MS, Sethi J, Taneja A, Musani A, Maldonado F. Computed tomography bronchus sign and the diagnostic yield of guided bronchoscopy for peripheral pulmonary lesions: a systematic review and meta-analysis. Ann Am Thorac Soc. 2018;15:978–87. ArticlePubMed
  • 15. Kim SH, Kim J, Pak K, Eom JS. Ultrathin bronchoscopy for the diagnosis of peripheral pulmonary lesions: a meta-analysis. Respiration. 2023;102:34–45. ArticlePubMedPMCPDF
  • 16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. ArticlePubMedPMC
  • 17. Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess. 2005;9:1–113. ArticlePDF
  • 18. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97–111. ArticlePubMedPDF
  • 19. Hunter JP, Saratzis A, Sutton AJ, Boucher RH, Sayers RD, Bown MJ. In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias. J Clin Epidemiol. 2014;67:897–903. ArticlePubMed
  • 20. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34. ArticlePubMedPMC
  • 21. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101. ArticlePubMed
  • 22. Oki M, Saka H, Asano F, Kitagawa C, Kogure Y, Tsuzuku A, et al. Use of an ultrathin vs thin bronchoscope for peripheral pulmonary lesions: a randomized trial. Chest. 2019;156:954–64. ArticlePubMed
  • 23. Fuso L, Varone F, Magnini D, Baldi F, Rindi G, Pagliari G, et al. Role of ultrasound-guided transbronchial biopsy in the diagnosis of peripheral pulmonary lesions. Lung Cancer. 2013;81:60–4. ArticlePubMed
  • 24. Tamiya M, Okamoto N, Sasada S, Shiroyama T, Morishita N, Suzuki H, et al. Diagnostic yield of combined bronchoscopy and endobronchial ultrasonography, under LungPoint guidance for small peripheral pulmonary lesions. Respirology. 2013;18:834–9. ArticlePubMed
  • 25. Tay JH, Irving L, Antippa P, Steinfort DP. Radial probe endobronchial ultrasound: factors influencing visualization yield of peripheral pulmonary lesions. Respirology. 2013;18:185–90. ArticlePubMed
  • 26. Chen A, Chenna P, Loiselle A, Massoni J, Mayse M, Misselhorn D. Radial probe endobronchial ultrasound for peripheral pulmonary lesions: a 5-year institutional experience. Ann Am Thorac Soc. 2014;11:578–82. ArticlePubMed
  • 27. Evison M, Crosbie PA, Morris J, Martin J, Barber PV, Booton R. Can computed tomography characteristics predict outcomes in patients undergoing radial endobronchial ultrasound-guided biopsy of peripheral lung lesions? J Thorac Oncol. 2014;9:1393–7. ArticlePubMed
  • 28. Kuo CH, Lin SM, Lee KY, Chung FT, Lo YL, Hsiung TC, et al. Endobronchial ultrasound-guided transbronchial biopsy and brushing: a comparative evaluation for the diagnosis of peripheral pulmonary lesions. Eur J Cardiothorac Surg. 2014;45:894–8. ArticlePubMed
  • 29. Sanchez-Font A, Giralt L, Vollmer I, Pijuan L, Gea J, Curull V. Endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions: a controlled study with fluoroscopy. Arch Bronconeumol. 2014;50:166–71. ArticlePubMed
  • 30. Asano F, Shinagawa N, Ishida T, Tsuzuku A, Tachihara M, Kanazawa K, et al. Virtual bronchoscopic navigation improves the diagnostic yield of radial-endobronchial ultrasound for peripheral pulmonary lesions with involved bronchi on CT. Intern Med. 2015;54:1021–5. ArticlePubMed
  • 31. Boonsarngsuk V, Kanoksil W, Laungdamerongchai S. Comparison of diagnostic performances among bronchoscopic sampling techniques in the diagnosis of peripheral pulmonary lesions. J Thorac Dis. 2015;7:697–703. PubMedPMC
  • 32. Chan A, Devanand A, Low SY, Koh MS. Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting. BMC Pulm Med. 2015;15:90.ArticlePubMedPMCPDF
  • 33. Guvenc C, Yserbyt J, Testelmans D, Zanca F, Carbonez A, Ninane V, et al. Computed tomography characteristics predictive for radial EBUS-miniprobe-guided diagnosis of pulmonary lesions. J Thorac Oncol. 2015;10:472–8. ArticlePubMed
  • 34. Minezawa T, Okamura T, Yatsuya H, Yamamoto N, Morikawa S, Yamaguchi T, et al. Bronchus sign on thin-section computed tomography is a powerful predictive factor for successful transbronchial biopsy using endobronchial ultrasound with a guide sheath for small peripheral lung lesions: a retrospective observational study. BMC Med Imaging. 2015;15:21.ArticlePubMedPMCPDF
  • 35. Oki M, Saka H, Ando M, Asano F, Kurimoto N, Morita K, et al. Ultrathin bronchoscopy with multimodal devices for peripheral pulmonary lesions: a randomized trial. Am J Respir Crit Care Med. 2015;192:468–76. ArticlePubMed
  • 36. Jacomelli M, Demarzo SE, Cardoso PF, Palomino AL, Figueiredo VR. Radial-probe EBUS for the diagnosis of peripheral pulmonary lesions. J Bras Pneumol. 2016;42:248–53. ArticlePubMedPMC
  • 37. Kunimasa K, Tachihara M, Tamura D, Tokunaga S, Nakata K, Hazeki N, et al. Diagnostic utility of additional conventional techniques after endobronchial ultrasonography guidance during transbronchial biopsy. Respirology. 2016;21:1100–5. ArticlePubMed
  • 38. Steinfort DP, Bonney A, See K, Irving LB. Sequential multimodality bronchoscopic investigation of peripheral pulmonary lesions. Eur Respir J. 2016;47:607–14. ArticlePubMed
  • 39. Wang C, Li X, Zhou Z, Zhao H, Li Z, Jiang G, et al. Endobronchial ultrasonography with guide sheath versus computed tomography guided transthoracic needle biopsy for peripheral pulmonary lesions: a propensity score matched analysis. J Thorac Dis. 2016;8:2758–64. ArticlePubMedPMC
  • 40. Asano F, Ishida T, Shinagawa N, Sukoh N, Anzai M, Kanazawa K, et al. Virtual bronchoscopic navigation without X-ray fluoroscopy to diagnose peripheral pulmonary lesions: a randomized trial. BMC Pulm Med. 2017;17:184.ArticlePubMedPMCPDF
  • 41. Huang CT, Ruan SY, Tsai YJ, Ho CC, Yu CJ. Experience improves the performance of endobronchial ultrasound-guided transbronchial biopsy for peripheral pulmonary lesions: a learning curve at a medical centre. PLoS One. 2017;12:e0179719ArticlePubMedPMC
  • 42. Eom JS, Mok JH, Kim I, Lee MK, Lee G, Park H, et al. Radial probe endobronchial ultrasound using a guide sheath for peripheral lung lesions in beginners. BMC Pulm Med. 2018;18:137.ArticlePubMedPMCPDF
  • 43. Good WR, Christensen PM, Herath S, Dawkins P, Yap E. Radial-probe endobronchial ultrasound outcomes in the investigation of peripheral pulmonary lesions: a New Zealand perspective. Intern Med J. 2018;48:1481–7. ArticlePubMedPDF
  • 44. Tanner NT, Yarmus L, Chen A, Wang Memoli J, Mehta HJ, Pastis NJ, et al. Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial. Chest. 2018;154:1035–43. ArticlePubMedPMC
  • 45. Zhang SJ, Zhang M, Zhou J, Zhang QD, Xu QQ, Xu X. Radial endobronchial ultrasonography with distance measurement through a thin bronchoscope for the diagnosis of malignant peripheral pulmonary lesions. Transl Lung Cancer Res. 2018;7:80–7. ArticlePubMedPMC
  • 46. Bo L, Li C, Pan L, Wang H, Li S, Li Q, et al. Diagnosing a solitary pulmonary nodule using multiple bronchoscopic guided technologies: a prospective randomized study. Lung Cancer. 2019;129:48–54. ArticlePubMed
  • 47. Kho SS, Chan SK, Yong MC, Tie ST. Performance of transbronchial cryobiopsy in eccentrically and adjacently orientated radial endobronchial ultrasound lesions. ERJ Open Res. 2019;5:00135–2019. ArticlePubMedPMC
  • 48. Xu C, Yuan Q, Wang Y, Wang W, Chi C, Zhang Q, et al. Usefulness of virtual bronchoscopic navigation combined with endobronchial ultrasound guided transbronchial lung biopsy for solitary pulmonary nodules. Medicine (Baltimore). 2019;98:e14248ArticlePubMedPMC
  • 49. Zhu J, Gu Y. Diagnosis of peripheral pulmonary lesions using endobronchial ultrasonography with a guide sheath and computed tomography guided transthoracic needle aspiration. Clin Respir J. 2019;13:765–72. ArticlePubMedPDF
  • 50. Boonsarngsuk V, Petnak T, So-Ngern A, Saksitthichok B, Kanoksil W. Comparison of different transbronchial biopsy sampling techniques for the diagnosis of peripheral pulmonary lesions with radial endobronchial ultrasound-guided bronchoscopy: a prospective study. Respir Investig. 2020;58:381–6. ArticlePubMed
  • 51. Samaranayake CB, Wright C, Erigadoo S, Azzopardi M, Putt M, Bint M. A randomized controlled trial on optimal sampling sequence in radial guide sheath endobronchial ultrasound lung biopsy. J Bronchology Interv Pulmonol. 2020;27:205–11. ArticlePubMed
  • 52. Goel MK, Kumar A, Maitra G, Singh B, Ahlawat S, Jain P, et al. Radial EBUS-guided cryobiopsy of peripheral lung lesions with flexible bronchoscopy without using guide-sheath. J Bronchology Interv Pulmonol. 2021;28:184–91. ArticlePubMed
  • 53. Hong KS, Ahn H, Lee KH, Chung JH, Shin KC, Jin HJ, et al. Radial probe endobronchial ultrasound using guide sheath-guided transbronchial lung biopsy in peripheral pulmonary lesions without fluoroscopy. Tuberc Respir Dis (Seoul). 2021;84:282–90. ArticlePubMedPMCPDF
  • 54. Jiang L, Xu J, Liu C, Gao N, Zhao J, Han X, et al. Diagnosis of peripheral pulmonary lesions with transbronchial lung cryobiopsy by guide sheath and radial endobronchial ultrasonography: a prospective control study. Can Respir J. 2021;2021:6947037.ArticlePubMedPMCPDF
  • 55. Zheng X, Xie F, Li Y, Chen J, Jiang Y, Sun J. Ultrathin bronchoscope combined with virtual bronchoscopic navigation and endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions with or without fluoroscopy: a randomized trial. Thorac Cancer. 2021;12:1864–72. ArticlePubMedPMCPDF
  • 56. Ito T, Matsumoto Y, Okachi S, Nishida K, Tanaka M, Imabayashi T, et al. A diagnostic predictive model of bronchoscopy with radial endobronchial ultrasound for peripheral pulmonary lesions. Respiration. 2022;101:1148–56. ArticlePubMedPDF
  • 57. Kim SH, Mok J, Jo EJ, Kim MH, Lee K, Kim KU, et al. The additive impact of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe on conventional biopsy for peripheral lung nodules. Cancer Res Treat. 2023;55:506–12. ArticlePubMedPMCPDF
  • 58. Lee J, Kim C, Seol HY, Chung HS, Mok J, Lee G, et al. Safety and diagnostic yield of radial probe endobronchial ultrasound-guided biopsy for peripheral lung lesions in patients with idiopathic pulmonary fibrosis: a multicenter cross-sectional study. Respiration. 2022;101:401–7. ArticlePubMedPDF
  • 59. Liu Y, Wang F, Zhang Q, Tong Z. Diagnostic yield of virtual bronchoscope navigation combined with radial endobronchial ultrasound guided transbronchial cryo-biopsy for peripheral pulmonary nodules: a prospective, randomized, controlled trial. Ann Transl Med. 2022;10:443.ArticlePubMedPMC
  • 60. Oki M, Saka H, Imabayashi T, Himeji D, Nishii Y, Nakashima H, et al. Guide sheath versus non-guide sheath method for endobronchial ultrasound-guided biopsy of peripheral pulmonary lesions: a multicentre randomised trial. Eur Respir J. 2022;59:2101678.ArticlePubMed
  • 61. Tanaka M, Matsumoto Y, Imabayashi T, Kawahara T, Tsuchida T. Diagnostic value of a new cryoprobe for peripheral pulmonary lesions: a prospective study. BMC Pulm Med. 2022;22:226.ArticlePubMedPMCPDF
  • 62. Zheng X, Zhong C, Xie F, Li S, Wang G, Zhang L, et al. Virtual bronchoscopic navigation and endobronchial ultrasound with a guide sheath without fluoroscopy for diagnosing peripheral pulmonary lesions with a bronchus leading to or adjacent to the lesion: a randomized non-inferiority trial. Respirology. 2023;28:389–98. ArticlePubMedPDF
  • 63. Ali MS, Trick W, Mba BI, Mohananey D, Sethi J, Musani AI. Radial endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions: a systematic review and meta-analysis. Respirology. 2017;22:443–53. ArticlePubMedPDF
  • 64. Huang CT, Ho CC, Tsai YJ, Yu CJ, Yang PC. Factors influencing visibility and diagnostic yield of transbronchial biopsy using endobronchial ultrasound in peripheral pulmonary lesions. Respirology. 2009;14:859–64. ArticlePubMed
  • 65. Folch EE, Labarca G, Ospina-Delgado D, Kheir F, Majid A, Khandhar SJ, et al. Sensitivity and safety of electromagnetic navigation bronchoscopy for lung cancer diagnosis: systematic review and meta-analysis. Chest. 2020;158:1753–69. ArticlePubMed
  • 66. Torky M, Elshimy WS, Ragab MA, Attia GA, Lopez R, Mate JL, et al. Endobronchial ultrasound guided transbronchial cryobiopsy versus forceps biopsy in peripheral lung lesions. Clin Respir J. 2021;15:320–8. ArticlePubMedPDF
  • 67. Ankudavicius V, Miliauskas S, Poskiene L, Vajauskas D, Zemaitis M. Diagnostic yield of transbronchial cryobiopsy guided by radial endobronchial ultrasound and fluoroscopy in the radiologically suspected lung cancer: a single institution prospective study. Cancers (Basel). 2022;14:1563.ArticlePubMedPMC
  • 68. Nadig TR, Thomas N, Nietert PJ, Lozier J, Tanner NT, Wang Memoli JS, et al. Guided bronchoscopy for the evaluation of pulmonary lesions: an updated meta-analysis. Chest. 2023;163:1589–98. ArticlePubMedPMC

Figure & Data

REFERENCES

    Citations

    Citations to this article as recorded by  

      • PubReader PubReader
      • ePub LinkePub Link
      • Cite
        CITE
        export Copy Download
        Close
        Download Citation
        Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.
        Format:
        • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
        • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
        Include:
        • Citation for the content below
        Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis
        Cancer Res Treat. 2024;56(2):464-483.   Published online November 29, 2023
        DOI: https://doi.org/10.4143/crt.2023.749
        Close
      • XML DownloadXML Download
      • 0
      • 1
      • 2
      • 3
      Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis
      Image Image Image Image
      Fig. 1. Flow diagram of search and study selection.
      Fig. 2. Funnel plot of publication bias.
      Fig. 3. Overall diagnostic yield of radial probe endobronchial ultrasound. CI, confidence interval; IV, inverse variance [22-62].
      Fig. 4. Diagnostic yield of radial probe endobronchial ultrasound based on sonographic findings [28,31,38,42,45-47,52,53,55,61,62]. (A) Within vs. adjacent to. (B) Within vs. invisible. (C) Adjacent to vs. invisible. CI, confidence interval.

      Fig. 1.

      Fig. 2.

      Fig. 3.

      Fig. 4.

      Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis
      Search strategy
      1 “Endobronchial ultrasound AND lung AND nodule(s)”
      2 “Endobronchial ultrasound AND lung AND lesion(s)”
      3 “Endobronchial ultrasound AND lung AND cancer(s)”
      4 “Endobronchial ultrasound AND pulmonary AND nodule(s)”
      5 “Endobronchial ultrasound AND pulmonary AND lesion(s)”
      6 “Endobronchial ultrasound AND pulmonary AND cancer(s)”
      7 “Endobronchial ultrasound AND peripheral AND nodule(s)”
      8 “Endobronchial ultrasound AND peripheral AND lesion(s)”
      9 “Endobronchial ultrasound AND peripheral AND cancer(s)”
      10 “Endobronchial ultrasonograph(y) AND lung AND nodule(s)”
      11 “Endobronchial ultrasonograph(y) AND lung AND lesion(s)”
      12 “Endobronchial ultrasonograph(y) AND lung AND cancer(s)”
      13 “Endobronchial ultrasonograph(y) AND pulmonary AND nodule(s)”
      14 “Endobronchial ultrasonograph(y) AND pulmonary AND lesion(s)”
      15 “Endobronchial ultrasonograph(y) AND pulmonary AND cancer(s)”
      16 “Endobronchial ultrasonograph(y) AND peripheral AND nodule(s)”
      17 “Endobronchial ultrasonograph(y) AND peripheral AND lesion(s)”
      18 “Endobronchial ultrasonograph(y) AND peripheral AND cancer(s)”
      19 “Radial probe AND lung AND nodule(s)”
      20 “Radial probe AND lung AND lesion(s)”
      21 “Radial probe AND lung AND cancer(s)”
      22 “Radial probe AND pulmonary AND nodule(s)”
      23 “Radial probe AND pulmonary AND lesion(s)”
      24 “Radial probe AND pulmonary AND cancer(s)”
      25 “Radial probe AND peripheral AND nodule(s)”
      26 “Radial probe AND peripheral AND lesion(s)”
      27 “Radial probe AND peripheral AND cancer(s)”
      No. Author/year Study design Selection criteria No. of lesions Diagnostic yield Prevalence of malignancy (%) Additional guidance Biopsy method Bronchoscope Complications Reference/Comparison test
      1 Fuso 2013 [23] Retrospective PLL not visible on routine bronchoscopy 447 0.77 80.3 None Forceps Standard 2 Bleed, 8 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
      2 Tamiya 2013 [24] Prospective PLL ≤ 30 mm 68 0.78 63.2 GS, Flu, VBN Brush, forceps, needle Thin NE Histology by alternative means or clinical/radiologic surveillance (6 mo)
      3 Tay 2013 [25] Retrospective PLL not visible on routine bronchoscopy 196 0.56 68.9 GS, Flu Brush, forceps NE NE Histology by alternative means or clinical/radiologic surveillance
      4 Chen 2014 [26] Retrospective NE 467 0.69 NE GS Brush, forceps, needle NE 6 Bleed, 13 PNX (7 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance
      5 Evison 2014 [27] Retrospective PLL not visible on routine bronchoscopy 117 0.69 82.9 GS Forceps Standard 6 Bleed 1 PNX (1 requiring chest tube), 2 poor tolerance to bronchoscope Clinical/radiologic surveillance (6 mo)
      6 Kuo 2014 [28] Retrospective PLL without endobronchial lesion, extrinsic compression, submucosal infiltration, or orifice narrowing 271 0.76 90.0 None Brush, forceps Standard 22 Bleed, 7 PNX NE
      7 Sanchez-Font 2014 [29] RCT PLL not visible on routine bronchoscopy 50 0.78 90.0 GS, Flu Brush, forceps Standard 9 Bleed Histology by alternative means or clinical/radiologic surveillance (6 mo)
      8 Asano 2015 [30] Retrospective PLL ≤ 30 mm 194 0.74 NE GS, Flu, VBN Brush, forceps Thin 1 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (24 mo)
      9 Boonsarngsuk 2015 [31] Prospective PLL with feeding bronchi, but not visible on routine bronchoscopy 112 0.80 67.9 GS, Flu Brush, forceps Standard 1 PNA Histology by alternative means or clinical/radiologic surveillance
      10 Chan 2015 [32] Retrospective Exclusion: PLL < 1 cm, endobronchial lesions, airway narrowing, pure GGO, absence of CT bronchus sign, presence of a submucosal lesion 120 0.69 63.3 GS, Flu Forceps Standard 7 Bleed, 1 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
      11 Guvenc 2015 [33] Retrospective Exclusion: bronchopneumonia, solid lesions < 10 mm, glass opacity (pure or part-solid less than 50%) lesions, solid lesions < 15 mm touching the visceral pleura 760 0.62 73.0 None Forceps Standard 9 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (6 mo)
      12 Minezawa 2015 [34] Retrospective PLL ≤ 30 mm 149 0.73 73.8 GS Brush, forceps Thin 1 Delirium, 4 PNA, 5 PNX Clinical/radiologic surveillance (12 mo)
      13 Oki 2015 [35] RCT PLL ≤ 30 mm 305 0.67 76.1 GS, Flu, VBN Forceps Thin, ultrathin 2 Bleed, 1 PNA, 8 PNX (3 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (12 mo)
      14 Jacomelli 2016 [36] Retrospective Pulmonary nodule or mass (non-diagnostic by routine bronchoscopy) 51 0.67 NE Flu Brush, forceps, needle Standard 5 Bleed, 2 PNX (2 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (6 mo)
      Exclusion: PLL with endobronchial lesions or lost to follow-up
      15 Kunimasa 2016 [37] Retrospective NE 88 0.82 97.7 GS, Flu Brush, forceps Thin NE Histology by alternative means or clinical/radiologic surveillance
      16 Steinfort 2016 [38] Prospective NE 245 0.58 82.4 ENB, GS, Flu, VBN Brush, forceps Thin NE Histology by alternative means or clinical/radiologic surveillance (12 mo)
      17 Wang 2016 [39] Prospective PLL in the outer 1/3 pulmonary field, invisible under routine bronchoscopy 54 0.82 87.0 GS, Flu Brush, forceps Thin 1 Bleed Histology by alternative means or clinical/radiologic surveillance
      18 Asano 2017 [40] RCT PLL > 30 mm 129 0.81 93.8 GS, Flu, VBN Brush, forceps Thin 2 Bleed, 1 hyperventilation, 1 PNA Histology by alternative means or clinical/radiologic surveillance (24 mo)
      Exclusion: endobronchial lesion, GGO lesion
      19 Huang 2017 [41] Retrospective PLL ≥ 8 mm, not visible on routine bronchoscopy 2,144 0.72 77.9 None Brush, forceps Thin 10 Bleed, 38 PNX Histology by alternative means or clinical/radiologic surveillance
      20 Eom 2018 [42] Retrospective NE 200 0.73 77.5 GS, Flu Brush, forceps Thin, 1 PNA, 2 PNX NE
      21 Good 2018 [43] Retrospective NE 68 0.56 75.0 GS Brush, forceps, needle NE 1 Dislodgement of GS, 3 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
      22 Tanner 2018 [44] RCT PLL 15-50 mm 112 0.49 75.0 GS, Flu Brush, forceps Standard, thin NE Histology by alternative means or clinical/radiologic surveillance (12 mo)
      23 Zhang 2018 [45] Retrospective Exclusion: Bronchial lesions on routine bronchoscopy, EBUS-GS TBB, malignant lesions without postoperative pathology, follow-up loss, or final diagnosis unknown 328 0.55 58.8 None Brush, forceps Thin 13 Bleed, 3 chest pain Histology by alternative means or clinical/radiologic surveillance
      24 Bo 2019 [46] RCT PLL with a high likelihood of malignancy, 8-30 mm 670 0.73 51.3 GS, VBN Forceps Thin 7 Bleed, 12 PNX (4 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (24 mo)
      25 Kho 2019 [47] Retrospective Exclusion: endobronchial lesion, incomplete clinical data, not visualized by RP-EBUS 114 0.68 NE GS, Flu Forceps, cryoprobe NE 24 Bleed, 1 PNX Histology by alternative means or clinical/radiologic surveillance
      26 Oki 2019 [22] RCT PLL ≤ 30 mm 356 0.64 79.2 GS, Flu, VBN Forceps, needle Thin, ultrathin 3 Bleed, 1 myocardial infarction, 1 nausea, 4 PNX (1 requiring chest tube), 1 vomiting Histology by alternative means or clinical/radiologic surveillance (12 mo)
      27 Xu 2019 [48] RCT PLL 8-30 mm 115 0.84 65.2 VBN Forceps Thin 1 Bleed, 1 PNX Histology by alternative means or clinical/radiologic surveillance (6 mo)
      28 Zhu 2019 [49] Retrospective NE 239 0.78 52.3 GS Forceps NE 21 Bleed, 2 chest pain, 18 fever, 2 PNA, 1 PNX, Histology by alternative means or clinical/radiologic surveillance
      29 Boonsarngsuk 2020 [50] Prospective PLL with feeding bronchi 90 0.82 77.8 GS, Flu Brush, forceps Thin NE Histology by alternative means or clinical/radiologic surveillance
      Exclusion: PLL < 10 mm, no feeding bronchi
      30 Samaranayake 2020 [51] RCT Exclusion: PLL < 15 mm, lack of bronchus sign, less than 180-degree view of the lesion on ultrasound, previous RP-EBUS TBB within 2 wk 54 0.78 81.5 GS, Flu Brush, forceps NE 7 Bleed Histology by alternative means or clinical/radiologic surveillance
      31 Goel 2021 [52] Retrospective NE 126 0.79 50.0 None Cryoprobe Standard 126 Bleed, 4 respiratory failure not requiring escalation of care NE
      32 Hong 2021 [53] Retrospective NE 607 0.76 61.4 GS Brush, forceps Thin 12 PNX (3 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (12 mo)
      33 Jiang 2021 [54] Prospective PLL 10-50 mm, solid or part-solid nodule, bronchus sign pulmonary nodule 59 0.70 NE GS, Flu, VBN Brush, cryoprobe, forceps Standard 8 Bleed, 2 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance (6 mo)
      Exclusion: endobronchial lesion, atelectasis, or obstructive
      34 Zheng 2021 [55] RCT PLL with the presence of the bronchus sign 120 0.78 83.3 Flu, VBN Brush, forceps Ultrathin None Histology by alternative means or clinical/radiologic surveillance (12 mo)
      Exclusion: endobronchial lesion, atelectasis, or obstructive pneumonia
      35 Ito 2022 [56] RCT PLL with no endobronchial lesion 1,634 0.70 84.8 GS, Flu, VBN Brush, forceps, needle NE NE Histology by alternative means or clinical/radiologic surveillance (24 mo)
      36 Kim 2023 [57] Retrospective PLL ≤ 30 mm 110 0.79 83.6 GS, Flu, VBN Brush, cryoprobe, forceps, needle Standard, thin, ultrathin 9 Bleed, 1 PNA, 1 PNX Histology by alternative means or clinical/radiologic surveillance (12 mo)
      37 Lee 2022 [58] Retrospective NE 954 0.75 NE GS, Flu Brush, forceps Thin 3 Bleed, 5 PNA, 2 PNX NE
      38 Liu 2022 [59] RCT PLL ≤ 30 mm, with the bronchial sign 138 0.74 69.6 GS, VBN Forceps, cryoprobe Standard 133 Bleed, 5 PNX Histology by alternative means or clinical/radiologic surveillance (6 mo)
      Exclusion: endobronchial lesion
      39 Oki 2022 [60] RCT PLL ≤ 30 mm 596 0.64 78.5 GS, Flu, VBN Brush, cryoprobe, forceps, needle Thin, ultrathin 1 Arrhythmia, 4 bleed (1 significant bleeding), 1 broken GS, 7 PNA, 8 PNX (4 requiring chest tube), 2 transient hypoxemia Histology by alternative means or clinical/radiologic surveillance (12 mo)
      40 Tanaka 2022 [61] Prospective PLL < 30 mm, located beyond the subsegmental bronchi 50 0.94 94.0 Flu, VBN Cryoprobe Thin 46 Bleed, 1 PNA, 1 PNX (1 requiring chest tube) Histology by alternative means or clinical/radiologic surveillance
      41 Zheng 2023 [62] RCT PLL ≥ 8 mm 426 0.84 80.8 GS, Flu, VBN Forceps, needle Thin 7 Bleed Histology by alternative means or clinical/radiologic surveillance (12 mo)
      Exclusion: absence of the bronchus sign, pure GGO, endobronchial lesion
      Variable No. of studies No. of lesions Pooled diagnostic yield (95% CI) Risk ratio (95% CI) Heterogeneity
      		 Overall effect
      χ2 I2 (%) p-value z p-value
      RP-EBUS findings (1 vs. 2, 1 vs. 3, 2 vs. 3) 12 1.45 (1.23-1.72) 47.3 77 < 0.001 4.37 < 0.001
      5 4.20 (1.89–9.32) 16.23 75 0.003 3.52 < 0.001
      5 2.59 (1.32-5.01) 12.60 68 0.013 2.75 0.006
       Within (1) 12 2,225 0.83 (0.80-0.86)
       Adjacent to (2) 12 670 0.57 (0.46-0.67)
       Invisible (3) 5 243 0.18 (0.06-0.43)
      Lesion characters (1 vs. 2, 1 vs. 3, 2 vs. 3) 7 1.15 (1.03-1.28) 11.04 46 0.087 2.59 0.010
      3 1.40 (0.93-2.11) 3.26 39 0.196 1.559 0.112
      2 1.39 (0.87-2.22) 0.67 0 0.414 1.39 0.166
       Solid (1) 8 2,894 0.73 (0.65-0.79)
       Part-solid (2) 7 597 0.58 (0.53-0.62)
       GGO (3) 3 46 0.52 (0.33-0.70)
      Lesion size (mm) 0.78 (0.73-0.83) 51.3 61 < 0.001 –7.49 < 0.001
       ≤ 20 21 2,380 0.58 (0.52-0.63)
       > 20 21 5,392 0.77 (0.73-0.80)
      Histologic diagnosis 1.30 (1.12-1.52) 473.4 94 < 0.001 3.33 < 0.001
       Malignancy 30 7,644 0.76 (0.72-0.79)
       Benign 30 2,320 0.57 (0.48-0.66)
      Bronchus sign 1.68 (1.32-2.14) 236.2 94 < 0.001 4.24 < 0.001
       Present 14 4,556 0.77 (0.72-0.82)
       Absent 14 1,231 0.44 (0.33-0.56)
      Distance from hilum 0.90 (0.84-0.96) 17.8 44 0.058 –3.38 < 0.001
       Peripheral 11 2,518 0.69 (0.61-0.76)
       Central and/or intermediate 11 1,360 0.76 (0.71-0.80)
      No. of studies No. of lesions Pooled diagnostic yield (95% CI) Heterogeneity
      		 Overall effect
      χ2 I2 (%) p-value χ2 p-value
      Combined adjunctive modalities 247.53 86 < 0.001 0.57 0.903
       Flu+GS 13 2,194 0.73 (0.67-0.78)
       Flu+GS+VBN 10 3,274 0.73 (0.67-0.79)
       GS 7 1,799 0.72 (0.68-0.76)
       None 6 4,076 0.70 (0.62-0.76)
      Single adjunctive modality
       GS 380.46 89 < 0.001 0.20 0.658
        Yes 31 8,196 0.72 (0.69-0.75)
        No 12 4,693 0.70 (0.62-0.78)
       Flu 377.65 89 < 0.001 0.01 0.929
        Yes 26 6,215 0.73 (0.69-0.77)
        No 17 6,674 0.73 (0.69-0.76)
       VBN 381.04 89 < 0.001 0.85 0.356
        Yes 16 4,724 0.74 (0.69-0.79)
        No 27 8,165 0.71 (0.68-0.74)
      Bronchoscopes 383.28 90 < 0.001 0.67 0.715
       Standard 12 2,363 0.71 (0.66-0.75) 66.69 84 < 0.001
       Thin 22 7,648 0.73 (0.68-0.78) 310.39 93 < 0.001
       Ultrathin 4 462 0.73 (0.69-0.77) 2.06 0 0.559
      Biopsy method
       Cryobiopsy 6 419 0.78 (0.70-0.85) 14.69 66 0.012
      Table 1. Search strategy for meta-analysis

      Table 2. Study characteristics

      CT, computed tomography; EBUS-GS, endbronchial ultrasound guide sheath; ENB, electromagnetic navigation bronchoscopy; Flu, fluoroscopy; GGO, ground glass opacity; GS, guide sheath; NE, not evaluable; PLL, peripheral lung lesion; PNA, pneumonia; PNX, pneumothorax; RCT, randomized controlled trial; RP-EBUS, radial probe endobronchial ultrasound; TBB, transbronchial biopsy; VBN, virtual bronchoscopic navigation.

      Table 3. Stratified meta-analysis for clinical factors

      CI, confidence interval; GGO, ground glass opacity; RP-EBUS, radial probe endobronchial ultrasound.

      Table 4. Stratified meta-analysis for technologies

      CI, confidence interval; Flu, fluoroscopy; GS, guide sheath; VBN, virtual bronchoscopic navigation.

      Table 1.

      Table 2.

      Table 3.

      Table 4.

      Cancer Res Treat : Cancer Research and Treatment
      © Korean Cancer Association.
      Close layer
      TOP