Current Role of EBUS/EUS November 16-17, 2012

1. Current Role of EBUS/EUSNovember 16-17, 2012 Traves D. Crabtree MD Department of Thoracic Surgery Washington University in St. Louis

2. Disclosures • Consultant/speakers bureau: Ethicon Endosurgery

3. Mediastinoscopy: The Gold Standard • Mortality 0.05%-0.08% • Morbidity 2% • Vocal cord injury, bleeding, tracheal injury, pneumothorax • Unable to access stations 5,6,8,9 • False negative rate reported to be 10-11% • Videomed. May decrease FN rate to 7% • ½ of FN may be station 8 and 9 mets Detterbeck et al. Chest 2007

4. Adequacy of Mediastinoscopy • Patient care survey of 729 hospitals • 40,090 patients, 11,668 treated surgically • Only 27% underwent mediastinoscopy • Only 46% resulted in lymph node tissue Little et al., Annals of Thoracic Surgery, 2005

5. Nodes Accessible by EBUS/EUS 5 8 9 Station 8 and 9 lymph nodes are inaccessible by EBUS

6. Crabtree T. Operative Techniques in Thoracic and Cardiovascular Surgery 2009 Outer diameter of EBUS scope is 6.7 mm for the shaft and 6.9 mm at the tip. .

7. Mediastinoscopy Volume in EBUS Era: 2007-11

8. Performance of Staging ToolsACCP Evidence-Based Clinical Practice Guidelines (2nd Ed) Conclusion: For enlarged N2 nodes, EUS/EBUS can be used to confirm diagnosis if positive, but if needle biopsy negative, cervical mediastinoscopy required Detterbeck et al. Chest 2007

9. EBUS Overall Performance Negative Predictive Value = TN/(TN+FN)

10. EBUS in a PET+ population • 106 patients underwent EBUS of PET+ nodes • Malignancy detected by EBUS in 56% • Biopsy performed in 30 of 46 EBUS negative • 3 of 30 positive for malignancy • Sensitivity 93%, Specificity 100%, NPV 91% • 63 out of 90 (70%) patients with malignant nodes Bauwens et al., Lung Cancer, 2008

11. EBUS in a CT - population • 100 patients underwent EBUS of CT- nodes (<1cm) • Malignancy detected by EBUS in 19% • Biopsy or resection performed in all, 2 additional + found • Sensitivity 91%, Specificity 100%, NPV 98% • 21 out of 100 (21%) patients with malignant nodes Herth et al., EurResp Journal, 2008

12. EBUS vs. Mediastinoscopy • 66 patients, enlarged level 2,4,or 7 lymph nodes • EBUS, then mediastinoscopy, then surgical resection • Very high rate of positive nodes (59/66 (89%)) • Med Sensitivity 68%, Specificity 100%, NPV 59% • EBUS Sensitivity 87%, Specificity 100%, NPV 78% • Largest difference in Med vs. EBUS at level 7 nodes Ernst et al., J Thoracic Oncology, 2008

13. Combined EBUS/EUS139 patients with suspected lung cancerUsed single EBUS scope for EUS and EBUS Herth et al. Chest 2010

14. Clinical Effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomized controlled trialAnnema et al. JAMA 2010Sharples et al. Health Technol Assess 2012 • 4 centers: Belgium, Netherlands, UK • Randomized to surgical staging alone (N=118) or EBUS/EUS followed by surgical staging only if EBUS/EUS negative (N=123) • Primary outcome sensitivity and NPV for the detection of N2/N3 disease, unnecessary thoracotomy, and complication rates. • Cost-utility also examined • Overall prevalance of nodal mets (N2N3) was 49%

15. ASTER trial Inclusion CriteriaAnnema et al. JAMA 2010Sharples et al. Health Technol Assess 2012 • Known or suspected NSCLC with suspected N2/N3 disease • Combination of EBUS and EUS performed by pulmonologist and gastroenterologist • Surgical staging via video mediastinoscopy • Chamberlain or VATS if necessary to stage

16. ASTER TrialAnnema et al. JAMA 2010Sharples et al. Health Technol Assess 2012 • Sensitivity for N2/N3 was 79% for surgical arm alone vs. 94% for EBUS/EUS (p=0.02) • NPV was 86% vs. 93% (p=0.26) • Complications were 6% in surgical arm and 5% in EBUS/EUS arm (p=0.78) • 18% unnecessary thoracotomies in surgical arm vs. 7% in EBUS/EUS arm (p=0.02) • EBUS/EUS strategy cheaper and more effective

17. Restaging Techniques after Induction TherapyAdapted from Crabtree, Broderick. Lung Cancer Management (in press)

18. EBUS-TBNA for Subtyping and Genotyping of NSCLCNavani et al. Am J RespCrit Care Med 2012 • Retrospective. 774 pts. 2009-2011 • 77% were adequately subtyped • 23% were NSCLC-NOS • EGFR mutation analysis was possible in 107/119 (90%) in whom mutation analysis was requested. • 1 reported death from pneumonia/sepsis

19. EBUS-TBNA Prevents Mediastinoscopies in the Diagnosis of Isolated Mediastinal Lymphadenopathy: The REMEDY TrialNavani et al. Am J RespirCrit Care Med Aug 2012 77 consecutive pts with MLND underwent EBUS-TBNA Diagnosis Made (N=67) 32 Sarcoidosis 26 TB 2 Lymphoma 4 Extra-Thoracic Ca 3 NSCLC No SpecificDx (N=10) Mediastinoscopy (N=10) EBUS NPV 40% Diagnosis Made (N=6) 2 Sarcoidosis 2 TB 1NSCLC 1 Lymphoma No Specific Dx (N=4) EBUS prevented 87% of mediastinoscopies Clinical &Radiological f/u (N=4) Diagnosis Made (N=4) 4 LN Hyperplasia

20. SUMMARY • If disease prevalence is high, EBUS at least equivalent to mediastinoscopy • If disease prevalence is low, EBUS results similar to mediastinoscopy • Negative EBUS results MAY need to be confirmed by med? • Combination of EBUS/EUS superior to EBUS alone • Role of EBUS to rule out lymphoma vs. inflammatory disease still uncertain

21. Other Issues to Consider • Where do you perform EBUS/EUS? • OR or endoscopy suite • Conscious sedation or general anesthesia? • How do you negotiate performing EBUS with your pulmonologists? • How do you negotiate EUS with your gastroenterologist? • How do you utilized ROSE (Rapid Onsite Evaluation)? • Do you perform other procedures at the same setting based on the EBUS/EUS results? • Startup costs?

22. CONCLUSION • EBUS/EUS WILL replace majority of mediastinoscopy procedures • Will you be doing it, or will someone else?