This document discusses mediastinal staging for non-small cell lung cancer. Accurate staging is needed to select the optimal treatment and predict prognosis. Imaging tests like CT have limitations while PET is more sensitive but lacks anatomical detail. PET/CT combines the metabolic data from PET with the anatomic images from CT to improve staging accuracy. A variety of minimally invasive and invasive surgical staging techniques can also be used.

1. MEDIASTINAL STAGING
FOR NON-SMALL CELL LUNG CANCER
Hong Kwan Kim
Samsung Medical Center
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2. WHY
MEDIASTINAL STAGING ?
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3. 12 5 7

4. O O O O
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5. O O O O
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6. Surgery
Radiotherapy
Chemotherapy
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7. Surgery
Local treatment
Radiotherapy
Chemotherapy
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8. Surgery
Local treatment
Radiotherapy
Systemic treatment
Chemotherapy
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9. Surgery
Local treatment Localized disease
Radiotherapy
Systemic treatment
Chemotherapy
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10. Surgery
Local treatment Localized disease
Radiotherapy
Systemic treatment Systemic disease
Chemotherapy
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11. Localized disease Systemic disease
?
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12. Localized disease Systemic disease
TNM staging !
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13. Localized disease Systemic disease
TNM staging !
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14. True Occult
Localized disease
localized systemic Systemic disease
disease Metastasis
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15. True Occult
Localized disease
localized systemic Systemic disease
disease Metastasis
N0 N1 N2 N3 M1
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16. Occult
systemic
Metastasis
N2 N3
Mediastinal LN metastasis
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17. N2 N3
M1
N0-1
Primary surgery
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18. N2 N3
ON0-1
M1
Primary surgery
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19. N2 N3
ON0-1 X
M1
Primary surgery
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20. N2
XX
N3
ON0-1
M1
Primary surgery
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21. ?X X N2 N3
ON0-1
M1
Primary surgery
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22. N2
Primary surgery
?
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23. N2 Multimodal approach !
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24. Accurate staging is needed
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25. Accurate staging is needed
To select the optimal treatment
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26. Accurate staging is needed
To select the optimal treatment
To predict prognosis after treatment
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27. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
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28. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
Sensitivity
TP
TP + FN
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29. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
Specificity
TN
FP + TN
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30. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
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31. Disease (+) Disease (-)
Test (+) TP FP PPV
Test (-) FN TN
TP
TP + FP
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32. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN NPV
TN
TN + FN
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33. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
Sensitivity Specificity
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34. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
Sensitivity Specificity
The prevalence of disease is already known
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35. Disease (+) Disease (-)
Test (+) TP FP
Test (-) FN TN
Sensitivity Specificity
The prevalence of disease is already known
Useful to compare different tests for the
same population
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36. Disease (+) Disease (-)
Test (+) TP FP PPV
Test (-) FN TN NPV
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37. Disease (+) Disease (-)
Test (+) TP FP PPV
Test (-) FN TN NPV
In the real practice, we don’t know the prevalence
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38. Disease (+) Disease (-)
Test (+) TP FP PPV
Test (-) FN TN NPV
In the real practice, we don’t know the prevalence
We only know that the patient has negative or
positive test
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39. Disease (+) Disease (-)
Test (+) TP FP PPV
Test (-) FN TN NPV
In the real practice, we don’t know the prevalence
We only know that the patient has negative or
positive test
More useful in an individual case
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40. Imaging
Needle
Surgical
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41. CT
Imaging PET
PET/CT
EUS
Needle TBNA
EBUS
Mediastinoscopy
Surgical Chamberlain
VATS
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42. CT
Imaging PET Non-invasive
PET/CT
EUS
Minimally
Needle TBNA
invasive
EBUS
Mediastinoscopy
Surgical Chamberlain Invasive
VATS
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43. CT
Imaging PET Non-invasive
PET/CT
EUS
Minimally
Needle TBNA
invasive
EBUS
Mediastinoscopy
Surgical Chamberlain Invasive
VATS
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44. CT
Imaging PET Non-invasive
PET/CT
Essential component of TNM staging
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45. 2007, Chest, Silvestri et al
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46. CT
Sensitivity 51%
Specificity 86%
2007, Chest, Silvestri et al
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47. CT
Sensitivity 51%
rate
Specificity 86%
Inaccu
2007, Chest, Silvestri et al
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48. Why inaccurate?
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49. Why inaccurate?
Only based on LN size (short axis diameter)
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50. Why inaccurate?
Only based on LN size (short axis diameter)
Benign Malignant
cm
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51. PET
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52. PET
Metabolic activity
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53. PET
Metabolic activity
Alteration in tissue metabolism precedes
anatomic change
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54. PET
Metabolic activity
Alteration in tissue metabolism precedes
anatomic change
More sensitive than CT
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55. 12 5 7

56. Anatomic resolution is limited in PET
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57. Anatomic resolution is limited in PET
PET/CT
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58. PET
Sensitivity 74%
Specificity 85%
2007, Chest, Silvestri et al
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59. PET
than CT
tter
Sensitivity 74%
Be Specificity 85%
2007, Chest, Silvestri et al
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60. PET
than CT
tter
Sensitivity 74%
Be Specificity 85%
ccu rate
Stil l ina
2007, Chest, Silvestri et al
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61. 12 5 7

62. FP rates are substantially high
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63. FP rates are substantially high
FN rates cannot be ignored
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64. False positives
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65. False positives
Inflammation (+)
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66. False positives
Inflammation (+) LN size
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67. False positives
Inflammation (+) LN size
FDG uptake
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68. False positives
Inflammation (+) LN size
FDG uptake
Granulomatous disease
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69. False positives
Inflammation (+) LN size
FDG uptake
Granulomatous disease
Postobstructive pneumonia
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70. False negatives
10mm
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71. False negatives
10mm 1mm
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72. False negatives
10mm 1mm 0.1mm
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73. False negatives
1,000,000,000
10mm 1mm 0.1mm
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74. False negatives
1,000,000,000 1,000,000
10mm 1mm 0.1mm
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75. False negatives
1,000,000,000 1,000,000 1,000
10mm 1mm 0.1mm
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76. False negatives
1,000,000,000 1,000,000 1,000
10mm 1mm 0.1mm
Imaging tests cannot detect these
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77. Malignant
Benign
Shadow is not real
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78. 12 5 7

79. Mediastinal staging solely based on
imaging tests is insufficient
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80. Mediastinal staging solely based on
imaging tests is insufficient
Tissue confirmation should be done!
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81. CT
Imaging PET Non-invasive
PET/CT
EUS
Minimally
Needle TBNA
invasive
EBUS
Mediastinoscopy
Surgical Chamberlain Invasive
VATS
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82. CT
Imaging PET Non-invasive
PET/CT
EUS
Minimally
Needle TBNA
invasive
EBUS
Mediastinoscopy
Surgical Chamberlain Invasive
VATS
Tissue confirmation
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83. EUS
Minimally
Needle TBNA
invasive
EBUS
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84. Conventional TBNA
(Transbronchial needle aspiration)
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85. Conventional TBNA
(Transbronchial needle aspiration)
Blind technique
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86. Conventional TBNA
(Transbronchial needle aspiration)
Blind technique
Operator dependent
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87. Conventional TBNA
(Transbronchial needle aspiration)
Blind technique
Operator dependent
Too high FN rate
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88. Endobronchial Ultrasound (EBUS)
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89. Endobronchial Ultrasound (EBUS)
Real-time biopsy
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90. Endobronchial Ultrasound (EBUS)
Real-time biopsy
Minimally invasive
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91. Endobronchial Ultrasound (EBUS)
Real-time biopsy
Minimally invasive
Safe
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92. Endobronchial Ultrasound (EBUS)
Real-time biopsy
Minimally invasive
Safe
Repeat-EBUS is easy
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93. Endobronchial Ultrasound (EBUS)
Real-time biopsy
Minimally invasive
Safe
Repeat-EBUS is easy
1, 2R, 4R, 2L, 4L, 7, 10
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94. Endobronchial Ultrasound (EBUS)
Real-time biopsy
Minimally invasive
Safe
Repeat-EBUS is easy
1, 2R, 4R, 2L, 4L, 7, 10
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95. 70 patients
Sensitivity 95.7%
Specificity 100%
2004, Chest,Yasufuku et al
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96. Endoscopic Ultrasound (EUS)
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97. Endoscopic Ultrasound (EUS)
Minimally invasive
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98. Endoscopic Ultrasound (EUS)
Minimally invasive
Safe
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99. Endoscopic Ultrasound (EUS)
Minimally invasive
Safe
4L, 5, 7, 8, 9
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100. Endoscopic Ultrasound (EUS)
Minimally invasive
Safe
4L, 5, 7, 8, 9
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101. 242 patients
Sensitivity 91%
Specificity 100%
2005, J Clin Oncol, Annema et al
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102. 12 5 7

103. 12 5 7

104. 12 5 7

105. 12 5 7

106. 2009, Eur J Cancer, Gu et al
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107. 93% 100%
2009, Eur J Cancer, Gu et al
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108. 12 5 7

109. 12 5 7

110. Biopsy is usually recommended for
patients with suspicious LN
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111. Biopsy is usually recommended for
patients with suspicious LN
High prevalence of LN metastasis
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112. Biopsy is usually recommended for
patients with suspicious LN
High prevalence of LN metastasis
Sensitivity can be overestimated
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113. n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) Test (+)
Test (-) Test (-)
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114. High prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) Test (+)
Test (-) Test (-)
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115. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) Test (+)
Test (-) Test (-)
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116. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) Test (+)
Test (-) Test (-)
Prevalence 80% vs 20%
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117. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 0 Test (+) 0
Test (-) Test (-)
Prevalence 80% vs 20%
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118. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 0 Test (+) 0
Test (-) 20 Test (-) 80
Prevalence 80% vs 20%
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119. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 0 Test (+) 0
Test (-) 5 20 Test (-) 5 80
Prevalence 80% vs 20%
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120. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 75 0 Test (+) 15 0
Test (-) 5 20 Test (-) 5 80
Prevalence 80% vs 20%
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121. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 75 0 Test (+) 15 0
Test (-) 5 20 Test (-) 5 80
Prevalence 80% vs 20%
Sensitivity vs
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122. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 75 0 Test (+) 15 0
Test (-) 5 20 Test (-) 5 80
Prevalence 80% vs 20%
Sensitivity 93.8% vs
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123. High prevalence Low prevalence
n=100 N2 (+) N2 (-) n=100 N2 (+) N2 (-)
Test (+) 75 0 Test (+) 15 0
Test (-) 5 20 Test (-) 5 80
Prevalence 80% vs 20%
Sensitivity 93.8% vs 75%
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124. 93% 100%
2009, Eur J Cancer, Gu et al
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125. 93% 100%
Prevalence 68%
2009, Eur J Cancer, Gu et al
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126. 12 5 7

127. Biopsy may be difficult for small-sized LN
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128. Biopsy may be difficult for small-sized LN
“Subcentimeter LN can be biopsied, but
there is a limit in sampling very small LN”
Yasufuku Kazuhiro
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129. Biopsy may be difficult for small-sized LN
“Subcentimeter LN can be biopsied, but
there is a limit in sampling very small LN”
Yasufuku Kazuhiro
N3 stations are usually skipped
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130. Non-diagnostic samples
vs
False-negative results
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131. 12 5 7

132. Nobody confirms positive EUS or EBUS
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133. Nobody confirms positive EUS or EBUS
...Any chance of false-positive results?
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134. Factors influencing EBUS results
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135. Factors influencing EBUS results
General anesthesia Conscious sedation
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136. Factors influencing EBUS results
General anesthesia Conscious sedation
21 gauge 22 gauge
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137. Factors influencing EBUS results
General anesthesia Conscious sedation
21 gauge 22 gauge
Thoracic surgeon Pulmonologist
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138. Factors influencing EBUS results
General anesthesia Conscious sedation
21 gauge 22 gauge
Thoracic surgeon Pulmonologist
Rapid On-Site Examination (cytopathologist)
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139. Factors influencing EBUS results
General anesthesia Conscious sedation
21 gauge 22 gauge
Thoracic surgeon Pulmonologist
Rapid On-Site Examination (cytopathologist)
Thoroughness of mediastinal LND
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140. 2007, Chest, Detterbeck et al
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141. 2007, Chest, Detterbeck et al
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142. 2007, Chest, Detterbeck et al
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143. N rates
Hig hF
2007, Chest, Detterbeck et al
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144. 2007, Chest, Detterbeck et al
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145. 2007, Chest, Detterbeck et al
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146. N rates
Hig hF
2007, Chest, Detterbeck et al
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147. 2007, Chest, Detterbeck et al
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148. “Negative results from EUS or EBUS should
be further confirmed by mediastinoscopy”
2007, Chest, Detterbeck et al
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149. Conventionally
the Gold Standard
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150. 2007, Chest, Detterbeck et al
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151. 2007, Chest, Detterbeck et al
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152. 2007, Chest, Detterbeck et al
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153. 12 5 7

154. 4L
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155. 4L
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156. 4L
7
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157. 4L
7
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158. 4L
7
4R
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159. 4L
7
4R
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160. There are many
inaccessible stations
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161. There are many
inaccessible stations
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162. Video mediastinoscope
Easier
Safer
More convenient
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163. Video mediastinoscope
Easier
Safer
More convenient
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164. 2011, JTCVS,Yasufuku et al
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165. 153 patients
2011, JTCVS,Yasufuku et al
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166. 153 patients
All patients underwent both EBUS
and mediastinoscopy
2011, JTCVS,Yasufuku et al
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167. All patients underwent both EBUS
153 patients
and mediastinoscopy
EBUS Mediastinoscopy
Sensitivity 81% 79%
NPV 91% 90%
p = .78
2011, JTCVS,Yasufuku et al
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168. 2010, JAMA, Annema et al
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169. Endosonography vs. Mediastinoscopy
Competitive?
2010, JAMA, Annema et al
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170. Endosonography vs. Mediastinoscopy
Competitive?
2010, JAMA, Annema et al
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171. Endosonography vs. Mediastinoscopy
Competitive?
2010, JAMA, Annema et al
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172. Endosonography vs. Mediastinoscopy
Complementary!
2010, JAMA, Annema et al
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173. Anyway,
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174. Anyway,
Tissue confirmation should be
routinely done?
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175. 2003, Ann Thorac Surg, Choi et al
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176. 291 patients (1995 ~ 2001)
2003, Ann Thorac Surg, Choi et al
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177. 291 patients (1995 ~ 2001)
Clinical stage I NSCLC
2003, Ann Thorac Surg, Choi et al
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178. 291 patients (1995 ~ 2001)
Clinical stage I NSCLC
N2 or N3 on mediastinoscopy
2003, Ann Thorac Surg, Choi et al
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179. 291 patients (1995 ~ 2001)
Clinical stage I NSCLC
N2 or N3 on mediastinoscopy
20 pts (6.9%)
2003, Ann Thorac Surg, Choi et al
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180. 291 patients (1995 ~ 2001)
Clinical stage I NSCLC
N2 or N3 on mediastinoscopy
20 pts (6.9%)
Routine mediastinoscopy is necessary
esp. for non-BAC type ADC
2003, Ann Thorac Surg, Choi et al
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181. 12 5 7

182. Ground glass opacity
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183. ADC in situ
Ground glass opacity
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184. GGO-type ADC is increasing
ADC in situ
Ground glass opacity
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185. 2010, Respirology, Park et al
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186. 147 patients
Clinical stage IA by PET/CT
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187. 147 patients
Clinical stage IA by PET/CT
78
Mediastinoscopy
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188. 147 patients
Clinical stage IA by PET/CT
78
Mediastinoscopy
3 75
N2 (+) N2 (-)
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189. 147 patients
Clinical stage IA by PET/CT
78 69
Mediastinoscopy
3 75 144
N2 (+) N2 (-) Thoracotomy
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190. 147 patients
Clinical stage IA by PET/CT
78 69
Mediastinoscopy
3 75 144
N2 (+) N2 (-) Thoracotomy
4 140
N2 (+) N2 (-)
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191. 12 5 7

192. Probability of occult LN metastasis
should be considered
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193. 2006, EJCTS, de Langen et al
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194. 2008, EJCTS, Al-Sarraf et al
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195. 2008, EJCTS, Al-Sarraf et al
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196. 2011, J Thorac Oncol, Kim et al
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197. 2011, J Thorac Oncol, Kim et al
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198. 2011, J Thorac Oncol, Kim et al
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199. Therefore,
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200. Therefore,
Mediastinal staging needs to be
individualized
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201. 2007, EJCTS, ESTS guideline
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202. PET or PET/CT
2007, EJCTS, ESTS guideline
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203. PET or PET/CT
Negative
2007, EJCTS, ESTS guideline
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204. PET or PET/CT
Negative
Surgery
2007, EJCTS, ESTS guideline
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205. PET or PET/CT
Negative Positive
Surgery
2007, EJCTS, ESTS guideline
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206. PET or PET/CT
Negative Positive
Tissue confirm
Surgery
2007, EJCTS, ESTS guideline
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207. PET or PET/CT
Negative Positive
Tissue confirm
Mediastinoscopy
Surgery
2007, EJCTS, ESTS guideline
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208. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy
Surgery
2007, EJCTS, ESTS guideline
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209. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Surgery
2007, EJCTS, ESTS guideline
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210. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Positive
Surgery
2007, EJCTS, ESTS guideline
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211. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Positive
Surgery Multimodal treatment
2007, EJCTS, ESTS guideline
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212. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Negative Positive
Surgery Multimodal treatment
2007, EJCTS, ESTS guideline
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213. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Negative Positive
Surgery Multimodal treatment
2007, EJCTS, ESTS guideline
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214. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Negative Positive Positive
Surgery Multimodal treatment
2007, EJCTS, ESTS guideline
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215. PET or PET/CT
Negative Positive
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Negative Positive Positive
Surgery Multimodal treatment
2007, EJCTS, ESTS guideline
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216. PET or PET/CT Central tumor
Low FDG uptake tumor
Negative Positive LN size > 1.5cm
PET N1 disease
Tissue confirm
EBUS / EUS
Mediastinoscopy Negative
Negative Positive Positive
Surgery Multimodal treatment
2007, EJCTS, ESTS guideline
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217. Take-home message
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218. Take-home message
Accurate mediastinal staging is important
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219. Take-home message
Accurate mediastinal staging is important
Mediastinal staging solely based on imaging
tests is insufficient due to high FP/FN rates
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220. Take-home message
Accurate mediastinal staging is important
Mediastinal staging solely based on imaging
tests is insufficient due to high FP/FN rates
Tissue confirmation can be done by EUS / EBUS
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221. Take-home message
Accurate mediastinal staging is important
Mediastinal staging solely based on imaging
tests is insufficient due to high FP/FN rates
Tissue confirmation can be done by EUS / EBUS
Negative results of needle techniques should be
further confirmed by surgical staging
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222. Tissue confirmation can be done by EUS / EBUS
Negative results of needle techniques should be
further confirmed by surgical staging
Probability of occult LN metastasis should be
considered
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223. Tissue confirmation can be done by EUS / EBUS
Negative results of needle techniques should be
further confirmed by surgical staging
Probability of occult LN metastasis should be
considered
Routine tissue confirmation regardless of
clinical characteristics should be re-considered
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224. 12 5 7

225. Thank you
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