Q J Med 2014; 107:201–206 doi:10.1093/qjmed/hct233 Advance Access Publication 19 November 2013
Impact of EBUS-TBNA on modalities for tissue acquisition in patients with lung cancer R.J. JOSE´1,2, P. SHAW3, M. TAYLOR3, D.R. LAWRENCE4, P.J. GEORGE1, S.M. JANES1,5 and N. NAVANI1,5 From the 1Department of Thoracic Medicine, 2Centre for Inflammation and Tissue Repair, UCL Respiratory 3Department of Radiology, 4Department of Cardiothoracic Surgery and 5Lungs for Living Research Centre, UCL Respiratory, University College Hospital, London, UK Address correspondence to: Dr Neal Navani, Department of Thoracic Medicine, University College London Hospital, 250 Euston road, London NW1 2PG, UK. email: [email protected] Received 10 October 2013 and in revised form 11 November 2013
Summary significantly increased from 0% in 2007 to 26.7% in 2009 and 25.4% in 2011 (P < 0.0001). In the same period there has also been an increased trend in the proportion of patients going directly to surgery without pathological confirmation with a 9.6% increase in diagnoses obtained at thoracotomy (P = 0.0526). Conclusions: The use of diagnostic modalities that provide information on diagnosis and staging in a single intervention are increasing. At our hospital, the use of EBUS-TBNA for providing a lung cancer diagnosis is increasing and this has led to a significant reduction in standard bronchoscopies and mediastinoscopies. These changes in practice may have implications for future service provision, training and commissioning.
Introduction The definitive treatment for patients with lung cancer is in part determined by the clinical staging of the disease. Therefore, it is important that the patient receives an accurate diagnosis of lung cancer and that delay in obtaining correct information on staging of the disease is avoided so that best definitive treatment can be commenced for the individual patient. This is especially important in the management of non-small cell lung cancer (NSCLC), where assessment of the mediastinum is essential to identify operable patients in the absence of extra-thoracic, contralateral lung or
pleural metastasis and to determine prognosis.1,2 The aim should be that all the required information should be obtained rapidly while performing the minimum number of diagnostic procedures. National Institute for Health and Care Excellence (NICE) guidance for the diagnosis and treatment of lung cancer, therefore recommends choosing ‘investigations that give the most information about diagnosis and staging with the least risk to the patient’.1 Depending on the site of the lesions and ease of access, various modalities can be used to obtain tissue for histological diagnosis.
! The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: [email protected]
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Background: The impact of the introduction of Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. Methods: A retrospective review of 328 consecutive patients diagnosed with lung cancer at a university teaching hospital, where they first presented in London in 2007, 2009 and 2011. EBUS was introduced in 2008. Results: In total, 316 patients were included in the analysis. Comparing 2007 with 2011 data, there has been a significant reduction in standard bronchoscopy (P < 0.0001) and mediastinoscopy (P = 0.02). The proportion of cases diagnosed by EBUS-TBNA
202
R.J. Jose´ et al.
Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive and safe technique that allows systematic assessment of mediastinal nodes to make an accurate diagnosis of lung cancer and other pathology (e.g. Sarcoidosis) and is suitable for subtyping of NSCLC and epidermal growth factor receptor (EGFR) mutation analysis.3,4 It is performed as an outpatient under conscious sedation and is well tolerated by patients.5 NICE has recommended EBUSTBNA as an initial investigation in patients with enlarged mediastinal lymph nodes and it is expanding as an important diagnostic modality in lung cancer, providing simultaneous information on lung cancer phenotype, genotype and nodal staging.1 The impact of the introduction of EBUSTBNA on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. Therefore, we have investigated the impact of the introduction of EBUS-TBNA in our hospital on other diagnostic modalities for tissue acquisition in patients with lung cancer.
We conducted a retrospective cohort analytical study of consecutive patients diagnosed with lung cancer at a university teaching hospital in London in 2007, 2009 and 2011. Patients were included for analysis only if they first presented to this hospital (referrals from other hospitals were excluded) and they were validated by comparison with the LUCADA database (National Lung Cancer audit database). EBUS-TBNA was introduced into routine clinical practice in 2008 and the learning curve was quickly surmounted.6 Data of 2009 and 2011 are included to demonstrate our change in practice over time following the introduction of EBUS. Data were collected on age, gender, performance status, diagnostic modality and pathological subtype from our electronic patient records and review of case notes. Patients where only a clinical diagnosis was made (n = 12) were excluded. Only the final diagnostic modality was included. For example, if EBUSTBNA was negative and subsequent tissue diagnosis was achieved by CT-guided lung biopsy, then only the CT-guided lung biopsy was registered as the diagnostic modality. Data were analysed using StatsDirect statistical software (version 2.7.9). For comparison between categorical variables, 2 or Fisher’s exact test were used as appropriate. The unpaired t-test was used for comparison of two continuous variables and the one-way analysis of variance for comparison of more than three continuous variables. All reported
Results In total, 316 patients had a histological diagnosis of lung cancer and were included in the analysis. In 2007, 2009 and 2011, 97, 101 and 118 patients, respectively presented to our hospital and had a histological diagnosis of lung cancer made. The mean [standard deviation (SD)] age was 68 (12) years for 2007, 67 (12) years for 2009 and 69 (12) years for 2011 (P = 0.595). The proportion of males was 62%, 55% and 63% for 2007, 2009 and 2011, respectively (P = 0.452). The results on performance status, histological subtype and staging for the 3 years are shown in Table 1. The results for the diagnostic modalities that provided the tissue for the histological diagnosis of each patient for the 3 years are listed in Table 2. Comparing 2007 with 2011 data, there has been a 24.8% reduction (38/97 in 2007 compared with 17/118) in 2011 in the proportion of histological diagnoses of lung cancer from tissue samples obtained by standard bronchoscopy [95% confidence interval (CI) 13.1–36.3%; P < 0.0001)] and a 4% reduction (4/97 compared with 0/118) in the proportion of histological diagnoses of lung cancer from tissue samples obtained by mediastinoscopy (95% CI 0.9–10.2%; P = 0.0200). The proportion of cases diagnosed by EBUS-TBNA significantly increased by 25.4% (95% CI 18.4–33.9%; P < 0.0001) between 2007 and 2011. There has also been a trend towards an increased proportion of patients going straight to surgery without pathological confirmation between 2007 and 2011 with a 9.6% (95% CI 0.6 to 19.7%, P = 0.0526) increase in diagnoses obtained at thoracotomy. Furthermore, there has been a reduction in diagnoses of NSCLC-NOS from 10.3% in 2007 to 2.5% in 2011 (P = 0.0216). Table 3 lists the lung cancer staging stratified by the diagnostic modality. EBUS has become the main diagnostic modality for the diagnosis of stage III lung cancer (42.3% increase from 2007 to 2011, 95% CI 25.4–61.2%; P < 0.0001) and for stage IV NSCLC (37.5% increase from 2007 to 2011, 95% CI 25.2– 51.7%, P < 0.0001).
Discussion This retrospective cohort study of consecutive histological diagnoses of lung cancer at a university teaching hospital in London demonstrates the impact of the introduction of EBUS-TBNA on the use of other diagnostic modalities for the acquisition
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Methods
P-values are exact two-tailed and are considered statistically significant when P < 0.05.
Using EBUS-TBNA in lung cancer diagnosis
203
Table 1 Performance status, histological subtype and lung cancer staging per year of diagnosis Year
Performance status
Histological subtype
Staging
0 1 2 3 4 Unknown Adenocarcinoma Adenosquamous Large cell NSCLC NOS Small cell Squamous cell 1 2 3 4 Unknown
2007 n = 97 n (%)
2009 n = 101 n (%)
2011 n = 118 n (%)
P-value
16 52 12 12 5 0 43 2 1 10 13 28 13 6 28 50 0
19 47 15 12 7 1 61 1 3 4 12 20 12 5 28 56 0
30 64 10 8 0 6 62 1 0 3 15 37 25 17 26 48 2
P = 0.016
(16.5) (53.6) (12.4) (12.4) (5.2) (0.0) (44.3) (2.1) (1.0) (10.3) (13.4) (28.9) (13.4) (6.2) (28.9) (51.5) (0.0)
(18.80) (46.50) (14.90) (11.90) (6.90) (1.00) (60.40) (1.00) (3.00) (4.00) (11.90) (19.80) (11.90) (5.00) (27.70) (55.40) (0.00)
(25.40) (54.20) (8.50) (6.80) (0.00) (5.10) (52.50) (0.80) (0.00) (2.50) (12.70) (31.40) (21.20) (14.40) (22.00) (40.70) (1.70)
P = 0.096
P = 0.027
Year
Standard bronchoscopy CT-guided lung biopsy Endobronchial ultrasound Extra-thoracic biopsy Liver biopsy Mediastinoscopy Other Pleural aspirate or biopsy Sputum cytology Thoracotomy US biopsy (lymph node) VATS excision biopsy
2007 Count (n = 97) n (%)
2009 Count (n = 101) n (%)
2011 Count (n = 118) n (%)
P-value (2007 vs. 2011)
38 16 0 6 4 4 1 5 2 12 8 1
17 30 27 2 2 0 2 6 0 4 5 6
17 19 30 6 3 0 0 4 0 26 9 4
Impact of EBUS-TBNA on modalities for tissue acquisition in patients with lung cancer R.J. JOSE´1,2, P. SHAW3, M. TAYLOR3, D.R. LAWRENCE4, P.J. GEORGE1, S.M. JANES1,5 and N. NAVANI1,5 From the 1Department of Thoracic Medicine, 2Centre for Inflammation and Tissue Repair, UCL Respiratory 3Department of Radiology, 4Department of Cardiothoracic Surgery and 5Lungs for Living Research Centre, UCL Respiratory, University College Hospital, London, UK Address correspondence to: Dr Neal Navani, Department of Thoracic Medicine, University College London Hospital, 250 Euston road, London NW1 2PG, UK. email: [email protected] Received 10 October 2013 and in revised form 11 November 2013
Summary significantly increased from 0% in 2007 to 26.7% in 2009 and 25.4% in 2011 (P < 0.0001). In the same period there has also been an increased trend in the proportion of patients going directly to surgery without pathological confirmation with a 9.6% increase in diagnoses obtained at thoracotomy (P = 0.0526). Conclusions: The use of diagnostic modalities that provide information on diagnosis and staging in a single intervention are increasing. At our hospital, the use of EBUS-TBNA for providing a lung cancer diagnosis is increasing and this has led to a significant reduction in standard bronchoscopies and mediastinoscopies. These changes in practice may have implications for future service provision, training and commissioning.
Introduction The definitive treatment for patients with lung cancer is in part determined by the clinical staging of the disease. Therefore, it is important that the patient receives an accurate diagnosis of lung cancer and that delay in obtaining correct information on staging of the disease is avoided so that best definitive treatment can be commenced for the individual patient. This is especially important in the management of non-small cell lung cancer (NSCLC), where assessment of the mediastinum is essential to identify operable patients in the absence of extra-thoracic, contralateral lung or
pleural metastasis and to determine prognosis.1,2 The aim should be that all the required information should be obtained rapidly while performing the minimum number of diagnostic procedures. National Institute for Health and Care Excellence (NICE) guidance for the diagnosis and treatment of lung cancer, therefore recommends choosing ‘investigations that give the most information about diagnosis and staging with the least risk to the patient’.1 Depending on the site of the lesions and ease of access, various modalities can be used to obtain tissue for histological diagnosis.
! The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: [email protected]
Downloaded from by guest on November 16, 2015
Background: The impact of the introduction of Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. Methods: A retrospective review of 328 consecutive patients diagnosed with lung cancer at a university teaching hospital, where they first presented in London in 2007, 2009 and 2011. EBUS was introduced in 2008. Results: In total, 316 patients were included in the analysis. Comparing 2007 with 2011 data, there has been a significant reduction in standard bronchoscopy (P < 0.0001) and mediastinoscopy (P = 0.02). The proportion of cases diagnosed by EBUS-TBNA
202
R.J. Jose´ et al.
Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive and safe technique that allows systematic assessment of mediastinal nodes to make an accurate diagnosis of lung cancer and other pathology (e.g. Sarcoidosis) and is suitable for subtyping of NSCLC and epidermal growth factor receptor (EGFR) mutation analysis.3,4 It is performed as an outpatient under conscious sedation and is well tolerated by patients.5 NICE has recommended EBUSTBNA as an initial investigation in patients with enlarged mediastinal lymph nodes and it is expanding as an important diagnostic modality in lung cancer, providing simultaneous information on lung cancer phenotype, genotype and nodal staging.1 The impact of the introduction of EBUSTBNA on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. Therefore, we have investigated the impact of the introduction of EBUS-TBNA in our hospital on other diagnostic modalities for tissue acquisition in patients with lung cancer.
We conducted a retrospective cohort analytical study of consecutive patients diagnosed with lung cancer at a university teaching hospital in London in 2007, 2009 and 2011. Patients were included for analysis only if they first presented to this hospital (referrals from other hospitals were excluded) and they were validated by comparison with the LUCADA database (National Lung Cancer audit database). EBUS-TBNA was introduced into routine clinical practice in 2008 and the learning curve was quickly surmounted.6 Data of 2009 and 2011 are included to demonstrate our change in practice over time following the introduction of EBUS. Data were collected on age, gender, performance status, diagnostic modality and pathological subtype from our electronic patient records and review of case notes. Patients where only a clinical diagnosis was made (n = 12) were excluded. Only the final diagnostic modality was included. For example, if EBUSTBNA was negative and subsequent tissue diagnosis was achieved by CT-guided lung biopsy, then only the CT-guided lung biopsy was registered as the diagnostic modality. Data were analysed using StatsDirect statistical software (version 2.7.9). For comparison between categorical variables, 2 or Fisher’s exact test were used as appropriate. The unpaired t-test was used for comparison of two continuous variables and the one-way analysis of variance for comparison of more than three continuous variables. All reported
Results In total, 316 patients had a histological diagnosis of lung cancer and were included in the analysis. In 2007, 2009 and 2011, 97, 101 and 118 patients, respectively presented to our hospital and had a histological diagnosis of lung cancer made. The mean [standard deviation (SD)] age was 68 (12) years for 2007, 67 (12) years for 2009 and 69 (12) years for 2011 (P = 0.595). The proportion of males was 62%, 55% and 63% for 2007, 2009 and 2011, respectively (P = 0.452). The results on performance status, histological subtype and staging for the 3 years are shown in Table 1. The results for the diagnostic modalities that provided the tissue for the histological diagnosis of each patient for the 3 years are listed in Table 2. Comparing 2007 with 2011 data, there has been a 24.8% reduction (38/97 in 2007 compared with 17/118) in 2011 in the proportion of histological diagnoses of lung cancer from tissue samples obtained by standard bronchoscopy [95% confidence interval (CI) 13.1–36.3%; P < 0.0001)] and a 4% reduction (4/97 compared with 0/118) in the proportion of histological diagnoses of lung cancer from tissue samples obtained by mediastinoscopy (95% CI 0.9–10.2%; P = 0.0200). The proportion of cases diagnosed by EBUS-TBNA significantly increased by 25.4% (95% CI 18.4–33.9%; P < 0.0001) between 2007 and 2011. There has also been a trend towards an increased proportion of patients going straight to surgery without pathological confirmation between 2007 and 2011 with a 9.6% (95% CI 0.6 to 19.7%, P = 0.0526) increase in diagnoses obtained at thoracotomy. Furthermore, there has been a reduction in diagnoses of NSCLC-NOS from 10.3% in 2007 to 2.5% in 2011 (P = 0.0216). Table 3 lists the lung cancer staging stratified by the diagnostic modality. EBUS has become the main diagnostic modality for the diagnosis of stage III lung cancer (42.3% increase from 2007 to 2011, 95% CI 25.4–61.2%; P < 0.0001) and for stage IV NSCLC (37.5% increase from 2007 to 2011, 95% CI 25.2– 51.7%, P < 0.0001).
Discussion This retrospective cohort study of consecutive histological diagnoses of lung cancer at a university teaching hospital in London demonstrates the impact of the introduction of EBUS-TBNA on the use of other diagnostic modalities for the acquisition
Downloaded from by guest on November 16, 2015
Methods
P-values are exact two-tailed and are considered statistically significant when P < 0.05.
Using EBUS-TBNA in lung cancer diagnosis
203
Table 1 Performance status, histological subtype and lung cancer staging per year of diagnosis Year
Performance status
Histological subtype
Staging
0 1 2 3 4 Unknown Adenocarcinoma Adenosquamous Large cell NSCLC NOS Small cell Squamous cell 1 2 3 4 Unknown
2007 n = 97 n (%)
2009 n = 101 n (%)
2011 n = 118 n (%)
P-value
16 52 12 12 5 0 43 2 1 10 13 28 13 6 28 50 0
19 47 15 12 7 1 61 1 3 4 12 20 12 5 28 56 0
30 64 10 8 0 6 62 1 0 3 15 37 25 17 26 48 2
P = 0.016
(16.5) (53.6) (12.4) (12.4) (5.2) (0.0) (44.3) (2.1) (1.0) (10.3) (13.4) (28.9) (13.4) (6.2) (28.9) (51.5) (0.0)
(18.80) (46.50) (14.90) (11.90) (6.90) (1.00) (60.40) (1.00) (3.00) (4.00) (11.90) (19.80) (11.90) (5.00) (27.70) (55.40) (0.00)
(25.40) (54.20) (8.50) (6.80) (0.00) (5.10) (52.50) (0.80) (0.00) (2.50) (12.70) (31.40) (21.20) (14.40) (22.00) (40.70) (1.70)
P = 0.096
P = 0.027
Year
Standard bronchoscopy CT-guided lung biopsy Endobronchial ultrasound Extra-thoracic biopsy Liver biopsy Mediastinoscopy Other Pleural aspirate or biopsy Sputum cytology Thoracotomy US biopsy (lymph node) VATS excision biopsy
2007 Count (n = 97) n (%)
2009 Count (n = 101) n (%)
2011 Count (n = 118) n (%)
P-value (2007 vs. 2011)
38 16 0 6 4 4 1 5 2 12 8 1
17 30 27 2 2 0 2 6 0 4 5 6
17 19 30 6 3 0 0 4 0 26 9 4
