Endoscopic and Endobronchial Ultrasound Staging for Lung Cancer. Michael B. Wallace, MD, MPH Professor of Medicine Mayo Clinic, Jacksonville

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1 Endoscopic and Endobronchial Ultrasound Staging for Lung Cancer Michael B. Wallace, MD, MPH Professor of Medicine Mayo Clinic, Jacksonville

2 Background: Lung Cancer 170,000 cases/yr in U.S. (# 1 cancer) Mediastinal Lymph Node (LN) dictates therapy No mediastinal LN: Surgery Ipsilateral LN: Neo-adjuvant +/- Surgery Contralateral LN: Chemo/XRT only EUS can access posterior mediastinum EBUS can access anterior med. and hilum

3 Why do Invasive Staging? Isn t t CT, PET good enough?

4 Integrated CT-PET Lardinois et al. NEJM 2003;348:2500

5 Case # 1 75 yom smoker with cough CXR-RUL RUL mass 3cm CT-Chest; Chest; 1.5cm pre-tracheal LN PET positive in mass, negative in LN

6 CT Scan Mass Lymph node (4R)

7 EBUS FNA

8 Role # 1 Confirmation of lymph node metastases when CT or PET is positive

9 Gress 1997 Larsen 2002 Kramer 2004 Larsen 2005 EUS Accuracy: CT positive Author (year) Silvestri 1996 Fritscher Ravens 2000 Wallace 2001 Wiersema 2001 Fritscher Ravens 2003 Annema 2004 Annema 2005 Annema 2005 Eloubeidi 2005 Wallace 2006 Summary N Sensitivity % Specificity % Detterbeck F, Wallace MB, Vansteenkiste J, et al. ACCP Staging Guidelines; Chest [in press]

10 Randomized Controlled Trial of Routine vs. Selected EUS-FNA Routine: All patients (with and w/o enlarged LN) Selected: EUS only if enlarged LN Outcome: Futile Thoracotomy Unresectable disease (N2/N3) Recurrent disease after surgery Larsen et al. Lung Cancer 2005;49:377

11 RCT of Routine vs. Selective EUS 53 randomized to routine EUS-FNA in 50/53 9% futile surgery (p 0.03) 4/54 died (8%) 51 randomized to selective EUS-FNA in 27% 25% futile surgery 8/51 died (16%)

12 Case 2 57 yom smoker with hemoptysis Good surgical candidate Chest CT 3.5 cm central RUL mass No mediastinal adenopathy PET postive in mass Negative in mediastinum

13 Case 2 If we go directly to OR, what percent of CT negative pts are found to have mediastinal LN 5% 10% 30% 50%

14 Case 2 If we go directly to OR, what percent of CT negative pts are found to have mediastinal LN 5% 10% 30% 50%

15 Case 2 FNA + NSCLC in 8mm subcarina LN

16 Role # 2 Detection of lymph node metastases when CT/PET are negative

17 EUS Accuracy: CT negative patients Author (year) N Sensitivity Specificity LeBlanc 2005 * (CT Negative) Wallace 2005 * (CT Negative) Summary Detterbeck F, Wallace MB, Vansteenkiste J, et al. ACCP Staging Guidelines; Chest [in press]

18 Case 3 81 yof had Squamous Cell Lung Ca 10 years prior Surgically excised T2N0 Yearly CT w/o disease until now New CT shows mass in LUL near aorta

19 Case 3

20 Case 3 Esophagus Aorta

21 Case 3? Transaortic FNA

22 EUS approach via Aorta Needle FNA showed NSCLC

23 Case 3 Thorascopic View 2 days later Needle path Mass Aorta esophagus Wallace et al. Ann Thor Surg, 2007

24 Role # 3 Staging and FNA of centrally located lung tumors

25 Accuracy of EUS in T4 staging in lung cancer Varadarajulu et al. GIE 2004;59:345-8

26 Accuracy of T staging by EUS T4 (gold standard) No T4 (gold standard) T4 by EUS No T4 by EUS Sensitivity: 88% Specificity: 98% Varadarajulu et al. GIE 2004;59:345-8

27 Case 4 49 yom with interstitial infiltrates and RLL consolidation? Post obstructive Bulky mediastinal and hilar LN PET positive in tumor and mediastinum

28 Case 4 Levels 7 and 11R

29 Case 4 EBUS FNA R Hilum FNA R Hilum, Subcarina: non-caseating Granuloma, AFB/Fungal cx negative DX: Sarcoidosis

30 Role # 4 Establishing (or excluding) a tissue diagnosis of cancer, sarcoid,, infection

31 Molecular Staging of Lymph Node Micrometastases with EUS-FNA and real-time PCR Wallace et al. Chest. 127:430-7, 7, 2005

32 Clinical Results Patients 38 Patients NSCLC 9 Path + mediastinal LN 40 Path mediastinal LN 48 Negative Controls (non cancer patients) 30 surgical lymph nodes 18 EUS-FNA of mediastinal LN

33 Future Roles Molecular Staging of Lung (and other) cancers

34 Detection of Micrometastases by RT PCR -2 Normal Control Cyto Positive Cyto Negative 3 8 Ct KS1/4 lunx muc1 CEA CK19 Gene

35 Sensitivity Receiver Operating Characteristic Curves (ROC) Path + vs. Control Area under Curve (AUC) KS ¼ 0.96 Muc CK CEA 0.80 Lunx Specificity KS1/4 CK19 muc1 lunx CEA

36 Detection of Micrometastases by RT PCR -2 Normal Control Cyto Positive Cyto Negative 3 8 Ct KS1/4 lunx muc1 CEA CK19 Gene

37 (Near) Future Roles Combined EUS + EBUS Complete Medical Mediastinoscopy

38 A prospective double blind comparison of endoscopic ultrasound, endobronchial ultrasound, and bronchoscopic fine needle aspiration for malignant mediastinal lymph nodes MB Wallace, JMS Pascual, M Raimondo, TA Woodward, B McComb, MM Johnson, M Al- Haddad, K Noh, S Pungpapong, J Hardee, O Pajaro, J Odell Mayo Clinic-Jacksonville, FL DDW 07

39 Results: Patients 150 Patients enrolled, 138 included 12 excluded: outside CT/PET unavailable All completed with conscious sedation No complications Wallace et al. DDW 07

40 Per Patient Accuracy Sensitivity Specificity 95% CI EUS-FNA 69%* 100% 53 82% EBUS-FNA 69%* 100% 53 82% TBNA 36% 100% 22 52% EUS-FNA + EBUS-FNA 93%** 100% 81 99% EUS-FNA + TBNA 79% 100% 63 90% EBUS-FNA + TBNA 76% 100% 61 88% Wallace et al. DDW 07 * p<0.01 vs TBNA, ** p<0.01 vs any single procedure

41 Negative Predictive Values PPV NPV 95% exact CI EUS-FNA 100% 88% 80 93% EBUS-FNA 100% 88% 80 93% TBNA 100% 78% 70 85% EUS-FNA + EBUS-FNA 100% 97% 91 99% EUS-FNA + TBNA 100% 91% 84 96% EBUS-FNA + TBNA 100% 91% 83 95% Wallace et al. DDW 07

42 Summary: Roles of EUS in Lung Cancer Lymph node staging CT/PET positive CT/PET negative Tumor staging and FNA Centrally located tumors only Combined EUS-EBUS EBUS for total staging? Molecular staging