1. Mediastinal staging in lung cancer Tuncay Göksel Ege Üniversitesi Tıp Fakültesi Göğüs Hastalıkları Anabilim Dalı Clinical and radiological staging is enough

2. DEFINITIONS

3. Mediastinoscopy: No Absolute T4 disease

4. Mediastinoscopy: Yes T1-3 N2 disease

5. Mediastinoscopy: ?+/-? Central TM or N1 disease

6. Mediastinoscopy: No T1-3 N0 disease

7. Sensitivity: 51% Specificity: 86% Mediastinal lymph node met. on CT Silvestri, Chest 2007; 132;178-201

8. Other metaanalysis CT & mediastinal nodes Gould et al –Sensitivity: 61% –Specificity: 79% Ann Intern Med 2003; 139:879–892 Dwamena et al –Sensitivity: 64% –Specificity: 74% Radiology 1999; 213:530–536 Daleset al –Sensitivity: 79% –Specificity: 78% Am Rev Respir Dis 1990; 141:1096–1101

9. Sensitivity: 74% Specificity: 85% Mediastinal lymph node met. on PET Silvestri, Chest 2007; 132;178-201

10. Meta-analysis of PET and CT in detecting mediastinal lymph node in NSCLC Birim et al, Ann Thorac Surg. 2005;79(1):375-82. Sensitivity (%)Specificity (%) PET66-100 (83)81-100 (92) BT20-81 (59)44-100 (78) PET > BT in diagnostic accuracy (all studies)

11. PET & CT for mediastinal staging, A meta-analysis Gould et al, Ann Intern Med 2003; 139:879–892

12. PET-CT vs PET Cerfolio, Ann Thorac Surg 2004;78:1017–23 Accuracy of of N2 –PET-CT > PET: (96% versus 93%, p 0.01) Accuracy of of N1 –PET-CT > PET: (90% versus 80%, p 0.001)

13. Sensitivity: 78% Specificity: 100% False negative: 11% Mediastinoscopy Detterbeck, Chest 2007; 132;202-220

14. The value of mediastinoscopy in NSCLC patients with clinical N0 diasease. Gürses, Turna, Bedirhan et al Thorac Cardiovasc Surg 2002; 50:174-177. 79 cases with CT negative  mediastinoscopy Negative prediktive value (all group) –CT  92,4% (73/79) –Mediastinoscopy  93,4% (57/61) p>0.05 Negative prediktive value (adenokarsinom) –CT  76,5% (13/17) –Mediastinoscopy  87,5% (15/17) p>0.05

15. Mediastinoscopy vs CT+Mediastinoscopy The Canadian Lung Oncology Group Ann Thorac Surg. 1995 Nov;60(5):1382-9 A randomized, controlled trial to decide on the necessity for mediastinoscopy in all cases –Mediastinoscopy in all cases –Mediastinoscopy only in patients with lymph node > 1 cm on CT Use of CT in comparison with mediastinoscopy in all patients strategy was likely to produce the same number of or fewer unnecessary thoracotomies

16. PET vs Mediastinoscopy Serra et al, ASCO 2006 Meeting Proceedings Clinic database review –655 routine mediastinoscopy –90 routine PET Understaged N2 (underwent to thoracotomy) –Routine PET+mediastinoscopy  7.8% –Routine mediastinoscopy  6.1% (p>0.05)

17. PET vs Mediastinoscopy Verhagen et al, Lung Cancer (2004) 44, 175—181 72 consecutive patients; PET vs mediastinoscopy PET, all cases –Negative predictive value: 71% –Positive predictive value : 83% Mediastinoscopy –Negative predictive value: 92 % –Positive predictive value : 100% PET, in patients with negative N1 nodes and a non-centrally tumor –Negative predictive value: 96% Negative PET in non-centrally tumor and without N1 node  mediastinoscopy should be omitted –This approach reduces the number of mandatory mediastinoscopy by 46% without an increase in unexpected N2

18. 2 R L 4 R L 7 Mediastinoscopy Bilateral paratracheal stationsBilateral paratracheal stations –2R, 2L, 4R, 4L Ant and proximal subcarinal stationAnt and proximal subcarinal station –7 5, 6 8,9

19. 42 to 57% of the FN cases were due to nodes that were not accessible by the mediastinoscope –(5,6,8,9 and part of 7) Coughlin, Ann Thorac Surg 1985; 40:556–560 Staples, Radiology 1988; 167:367–372 Gdeedo, Eur Respir J 1997; 10: 1547–1551 Van den Bosch, J Thorac Cardiovasc Surg 1983; 85:733–737 Hammoud, J Thorac Cardiovasc Surg 1999; 118:894–899 Lardinois, Ann Thorac Surg 2003; 75:1102–1106 False negative cases on mediastinoscopy

20. The yield of mediastinoscopy Fibla et al, J Thorac Oncol 2006; 1: 430-33 False negative: 19.6%

21. Location of tumor & the most common lymph node metastasis Tumors in –the right upper lobe  4R and 2R stations –the right middle lobe  7 station –the right lower lobe  4R and 7 stations –the left upper lobe  5 and 6 stations –the left lower lobe  5 and 7 stations Cerfolio, Ann Thorac Surg 2006; 81:1969–1973 Kotoulas, Lung Cancer2004; 44:183–191 Naruke T, Eur J Cardiothorac Surg 1999; 16:S17–S24

22. Right upper #7,8,9: 12% #8,9: 0.5% Right middle #7,8,9: 27% #8,9: 0% Right lower #7,8,9: 42% #8,9: 4%

23. Naruke T, Eur J Cardiothorac Surg 1999; 16:S17–S24 Left upper lobe #5,6,7,8,9: 66% #5,6,8,9: 56% Left lower lobe #5,6,7,8,9: 68% #5,6,8,9: 28%

24. Improving the inaccuracies of clinical staging Cerfolio et al, Ann Thorac Surg. 2005 Oct;80(4):1207-13 A prospective trial to compare clinical stage and pathologic stage RoutinE PET/CT –Clinical N0  thoracotomy –Clinical N2  Mediastinoscopy was used to biopsy for 2R, 4R, 2L, 4L, ant 7 EUS+TBNA was used to biopsy for posterior N2 (5, 7, 8, and 9) Unsuspected N2: PET/CT or CT scan negative (clinically called N2 negative) but pathologically metastatic

25. Improving the inaccuracies of clinical staging Cerfolio et al, Ann Thorac Surg. 2005 Oct;80(4):1207-13

26. Unsuspected N2  #7 : 52% #5-6 : 24% #2-4R : 16% #8-9 : 8%

27. Routine mediastinoscopy and EUS+FNA in patients with clinically N2 negative Cerfolio et al, CHEST 2006; 130:1791–1795 A prospective trial, NSCLC –Clinically staged N2 negative by both PET/CT and CT scan. –Routine both mediastinoscopy and EUS-FNA Mediastinoscopy was used to biopsy for 2R, 4R, 2L, 4L, ant 7 EUS+TBNA was used to biopsy for 5, 7, 8, and 9

28. Cerfolio et al, CHEST 2006; 130:1791–1795 4.4%

29. Conclusion Routine mediastinoscopy or EUS-FNA –it is not recommended in clinically N0 but it is recommended in clinically N1 Since N2 disease was more often located in the posterior mediastinal lymph nodes that are not accessible via mediastinoscopy, EUS-FNA should be added to the algorithm. Routine Mediastinoscopy and EUS+FNA in Patients With Clinically N2 Negative Cerfolio et al, CHEST 2006; 130:1791–1795

30. EUS+FNA in patients with negative mediastinoscopy Eloubeidi,Ann Thorac Surg 2005;80:1231– 40 35 patients who had a prior negative mediastinoscopy EUS TBNA –13 patients (37.1%) had malignant N2 or N3 Cost for per patient (avarage) –Initial EUS-FNA: $1,867 –Initial mediastinoscopy: $12,900

31. EUS FNA Detterbeck, Chest 2007; 132;202-220 Sensitivity: 84% Specificity: 99.% False negative: 19%

32. Sensitivity: 90% Specificity: 100% False negative: 20% EBUS TBNA Detterbeck, Chest 2007; 132;202-220

33. MediastinoscopyEUS-FNAEBUS-TBNA 2R ant. Trachea 2L 2R 4R 4L 755 77 810R 910L Left adrenal11

34. EBUS in negative mediastinum in the CT-Scan Herth, et al, Eur Respir J 2006 Nov; 28 (5):910-4 100 patients with NSCLC 119 lymph nodes punctured all LN controlled by surgery Sensitivity: 92.3% Specificity: 100.0% NPV: 96.3%

35. Comparison of EBUS, PET, CT in staging in lung cancer Yasufuku, Chest 2006; 130; 710-718 Prospective study 102 patients with NSCLC all patients planned for surgery

36. Detterbeck FC et. Al. Chest 2007; 132: 202S-220S TBNA Specimen adequate: 80–90% Sensitivity: 78% False negative rate: 28% Specifity: 99% False positive rate: 1% TBNA 2R, 2L, 4R, 4L 7 10R, 10L, 11

37. 19 patients N2 positive induction chemotherapy Re-staging by EUS TBNA Sensitivity: 75% Specificity: 100% EUS-FNA for mediastinal restaging after induction CT for NSCLC Annema et al., Lung Cancer 2003;42:311-18.

38. 123 patients N2 positive Induction chemotherapy Restaging by EUS TBNA Sensitivity: 76% Specificity: 100% Accuracy : 77% EBUS-TBNA for mediastinal restaging after induction CT for NSCLC Herth et al, Chest 2007 Vol 132 (S4): 466S

39. Summary-1 Specificity is more important than sensitivity for CT and PET because of exclusion –CT  specificity: 86% –PET  specificity: 85% –<1 cm LAP on CT: PET  specificity: 93% –Negative N1 nodes and a non-centrally tumor  NPV: 96% The specificity and the FP of mediastinoscopy  100% and 0% –Reliably? No confirmation such as thoracotomy Understaged N2 (unnecessary thoracotomy) –Routine CT+mediastinoscopy or Routine PET+mediastinoscopy same or fewer

40. The yield of mediastinoscopy is low in –node < 1cm  8.5% –squamous and clinical N0  3.3% –Left lobe tumor 18.6% FN 11% of mediastinoscopy –50% of the FN  not accessible by the mediastinoscopy (#5,6,8,9 and part of 7) –~30-66% left lung  # 5,6,8,9,7 –Risk of N2-3  5-8% in Clinically N0  20-30% in Clinically N1 (but majority is posterior N2) Summary-2

41. EUS and EBUS –Specifity and sensitivite ↑↑ as mediastinoscopy –Detecting of N2-3 in clinically N0 EUS or EBUS  mediastinoscopy –Re-staging after induction CT EBUS and EUS are successful (hopeful) Summary-3

42. Conclusion Today Routine mediastinoscopy  NO NO –cN0 disease –cN1 disease in left lung –Absolute T4 YES –cN2 disease –cN1 disease in right lung

43. Conclusion Future Routine mediastinoscopy  NO NO –cN0 disease –Absolute T4 –cN2 disease –cN1 disease EBUS EUS