Congreso para cirugía de tórax, Medellín, Hotel InterContinental, Mayo 21 de 2018

1. Mediastinal Staging in Clinical Stage I and II NSCLC
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín, Colombia
Medellín, 21.05.2018

2. Conflicts of interest for this lecture
Mauricio Lema
None for this lecture

3. @onconerd

6. Mediastinal LN status MUST be as
accurate as posible BEFORE undergoing
surgery with curative intent

7. Importance of N status in M0 NSCLC
cT1-3 cN0/N1 cT1-3 cN3cT1-3 cN2
Surgery
Pre-Op/Definitive
Chemo-RT
Definitive Chemo-RT

9. CT-scan
Contrast-enhanced
Thorax, liver & adrenal
Silvestri GA, et al. Chest, 2013
Radiographic group A: mediastinal infiltration that encircles
the vessels and airways, so that discrete lymph nodes can
no longer be discerned or measured
Radiographic group B: mediastinal infiltration in whom the
size of discrete nodes can be measured
Radiographic group C: central tumor (within proximal 1/3
of the thorax) or suspected N1 disease (Level 10 ≥1 cm)
(N2/N3 risk in the 20-25% range).
Radiographic group D: peripheral clinical stage I

10. CT-scan
“For patients with extensive mediastinal
infiltration of tumor and no distant metastases,
it is suggested that radiographic (CT)
assessment of the mediastinal stage is usually
sufficient without invasive confirmation”
Silvestri GA, et al. Chest, 2013
RUL cancer
Radiographic groups A and B

11. CT-scan
“…the most widely used
criterion is a short-axis lymph
node diameter of 1 cm on a
transverse CT scan.”
Silvestri GA, et al. Chest, 2013

12. CT-scan
“…the most widely used
criterion is a short-axis lymph
node diameter of 1 cm on a
transverse CT scan.”
Prenzel KL, Chest, 2003
2891 resected hilar and mediastinal nodes
101/139 (77%) patients with pN0 had at least 1
node > 1 cm
256 patients
14/117 (12%) patients with pN2/pN3 had no
nodes greater than > 1 cm

13. CT-scan
“…the most widely used
criterion is a short-axis lymph
node diameter of 1 cm on a
transverse CT scan.”
Silvestri GA, et al. Chest, 2013

14. CT-scan
“…the most widely used
criterion is a short-axis lymph
node diameter of 1 cm on a
transverse CT scan.”
Silvestri GA, et al. Chest, 2013
Sens Spec PPV NPV

15. 15
Mediastinal Staging with Chest CT
Sensitivity
PPV
Specificity
NPV
Prevalence of mediastinal metastasis
55%
58%
81%
83%
30%

16. Excellent Acceptable Insufficient Useless

17. 17
Mediastinal Staging with Chest CT
Sensitivity
PPV
Specificity
NPV
Prevalence of mediastinal metastasis
55%
58%
81%
83%
30%

18. 18
Mediastinal Staging with Chest CT
Clinical stage I
5-15% mediastinal LN involvement
CT-Chest: N0
The American Thoracic Society and The European Respiratory Society. Pretreatment evaluation of non-small-cell
lung cancer. Am J Respir Crit Care Med . 1997 ; 156 ( 1 ): 320 - 332

19. 19
Mediastinal Staging with Chest CT
Clinical stage I
5-15% mediastinal LN involvement
CT-Chest: N0
The American Thoracic Society and The European Respiratory Society. Pretreatment evaluation of non-small-cell
lung cancer. Am J Respir Crit Care Med . 1997 ; 156 ( 1 ): 320 - 332

20. "but it remains the best overall anatomic study available for the thorax.
CT scanning usually guides the choice of nodes for selective node biopsy
by invasive techniques, and thus continues to be an important
diagnostic tool in lung cancer.
The choice of individual nodes for sampling, as well as the choice of the
most appropriate invasive technique (including transbronchial,
transthoracic, or transesophageal NA; mediastinoscopy; or more
extensive surgery), are typically directed by the findings of the CT scan"
Mediastinal Staging with Chest CT
Silvestri GA, et al. Chest, 2013

21. Can we improve on mediastinal
staging with CT-scan?

22. Lymph node stations Descriptor Abnormal size (short axis)
1 Highest mediastinal
2 Upper para-tracheal >7 mm
3 Pre-vascular / retro-tracheal
4 Lower para-tracheal >9 mm
5 Sub-aortic (AP window) >8 mm
6 Para-aortic >8 mm
7 Sub-carinal >12 mm
8L Para-oesophageal >7 mm
8R Para-oesophageal >10 mm
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

23. Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

24. RUL
RML
2R
4R
10R
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

25. RUL
RML
2R
4R
10R
LUL
2L
4L
6
5
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

26. RLL
8R
RLL8L
7
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

27. RUL
RML
2R
4R
10R
RLL
8R
LUL
2L
4L
6
RLL8L
7
5
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

28. High-risk LN station for primary
tumor location?
Short-axis size > than normal?
Central LN lipomatosis or
calcification
Non-pathologic LN
Pathologic LN
Non-pathologic
LN
Yes
YesNo
NoYes
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.

29. MSCT multi-criteria: a novel approach in assessment of mediastinal
lymph node metastases in non-small cell lung cancer.
Volterrani L. Eur J Radiol. 2011 Sep;79(3):459-66.
86 consecutive patients with histopathologically proven NSCLC. All patients underwent surgical lymph node resection
within 30 days from the CT examination. In all cases pathological and CT results were reviewed and correlated.

30. 30
Mediastinal Staging with MSCT-multicriteria
Sensitivity
PPV
Specificity
NPV
94-100%
94%
98.5%
98.5-100%

31. ?

32. 32
Mediastinal Staging with MSCT-multicriteria
Sensitivity
PPV
Specificity
NPV
94-100%
94%
98.5%
98.5-100%

33. 33
Mediastinal Staging with MSCT-multicriteria
Sensitivity
PPV
Specificity
NPV
94-100%
94%
98.5%
98.5-100%
If confirmed

34. PET-CT
With FDG
Patients with known NSCLC and no suspicious extra thoracic abnormalities on chest
CT, additional imaging for metastases is recommended (ie, PET-CT)
Silvestri GA, et al. Chest, 2013

35. Silvestri GA, et al. Chest, 2013
PET-CT

36. Silvestri GA, et al. Chest, 2013
PET-CT

37. PET-CT
With FDG
Patients with known NSCLC and no suspicious extra thoracic abnormalities on chest
CT, additional imaging for metastases is recommended (ie, PET-CT)
Silvestri GA, et al. Chest, 2013
A reduction, from approximately 40% to 20%, in the
number of non curative resections performed
(defined as the presence of benign disease,
unsuspected N2 involvement, unresectable disease,
or death from any cause within 1-yr).

38. PET-CT
Meta-analysis of PET + CT in
mediastinal staging of NSCLC
n= 4105 patients
Silvestri GA, et al. Chest, 2013

39. PET-CT
Meta-analysis of PET + CT in
mediastinal staging of NSCLC
n= 4105 patients
Silvestri GA, et al. Chest, 2013

40. PET-CT
Meta-analysis of PET + CT in
mediastinal staging of NSCLC
n= 4105 patients
Silvestri GA, et al. Chest, 2013
Sens Spec PPV NPV

41. PET-CT
Meta-analysis of PET + CT in mediastinal
staging of NSCLC
Years 2004-2011
n= 2,014 patients
Silvestri GA, et al. Chest, 2013

42. 42
Mediastinal Staging with PET-CT
Sensitivity
PPV
Specificity
NPV
Prevalence of mediastinal metastasis
80%
75%
88%
91%
28%

43. “In nodes less than 1 cm, the sensitivity of FDG-PET-CT to detect nodal
metastasis is not optimal and has been reported as sensitivity or 32.4%
versus 85.3% in nodes greater than or equal to 1 cm.”
Billé A, et al. Eur J Cardiothoracic Surg, 2009

44. 44
Mediastinal Staging with PET-CT
Clinical peripheral stage I
4% mediastinal LN involvement
PET-CT: N0
Kozower BD , Meyers BF , Reed CE , Jones DR , Decker PA , Putnam JB Jr . Does positron emission tomography
prevent nontherapeutic pulmonary resections for clinical stage IA lung cancer? Ann Thorac Surg . 2008 ; 85 ( 4 ):
1166 - 1169.

45. 45
Mediastinal Staging with PET-CT
Clinical peripheral stage I
4% mediastinal LN involvement
PET-CT: N0
Kozower BD , Meyers BF , Reed CE , Jones DR , Decker PA , Putnam JB Jr . Does positron emission tomography
prevent nontherapeutic pulmonary resections for clinical stage IA lung cancer? Ann Thorac Surg . 2008 ; 85 ( 4 ):
1166 - 1169.

46. "One should not preclude a potential curative surgery based on a
positive PET scan alone without tissue confirmation."
Mediastinal Staging with PET CT
Silvestri GA, et al. Chest, 2013

47. "However, PET scanning is the most accurate noninvasive imaging
modality available to evaluate the mediastinum in patients with lung
cancer.
PET scanning is also a whole-body study (excluding the brain), offers
additional information relating to extrathoracic sites of possible disease
involvement, and can reduce noncurative resections.
PET scanning has now assumed a central role in the staging of lung
cancer.”
Mediastinal Staging with PET CT
Silvestri GA, et al. Chest, 2013

48. Can we improve on mediastinal
staging with PET-CT?

49. Neural Networks for Nodal Staging of Non–Small Cell Lung Cancer with
FDG PET and CT: Importance of Combining Uptake Values and Sizes of
Nodes and Primary Tumor
Toney LK, Radiology, 2014
“The authors developed a back-
propagation ANN with one hidden layer
and eight processing units”.

50. Neural Networks for Nodal Staging of Non–Small Cell Lung Cancer with
FDG PET and CT: Importance of Combining Uptake Values and Sizes of
Nodes and Primary Tumor
Toney LK, Radiology, 2014

51. Neural Networks for Nodal Staging of Non–Small Cell Lung Cancer with
FDG PET and CT: Importance of Combining Uptake Values and Sizes of
Nodes and Primary Tumor
Toney LK, Radiology, 2014

52. 52
Mediastinal Staging with ANN PET-CT
Correct prediction of N stage
Correct prediction of N0/1 vs N2/3
99%
99%
72%
92%
ANN Expert reader
ANN: Artificial Neural Network
Toney LK, Radiology, 2014

53. 53
Mediastinal Staging with ANN PET-CT
Correct prediction of N stage
Correct prediction of N0/1 vs N2/3
99%
99%
72%
92%
ANN Expert reader
ANN: Artificial Neural Network
Toney LK, Radiology, 2014

54. 54
Mediastinal Staging with ANN PET-CT
Correct prediction of N stage
Correct prediction of N0/1 vs N2/3
99%
99%
72%
92%
ANN Expert reader
ANN: Artificial Neural Network
Toney LK, Radiology, 2014
If confirmed

55. ?

56. Pancoast syndrome is characterized by a
malignant neoplasm of the superior sulcus of the
lung with destructive lesions of the thoracic inlet
and involvement of the brachial plexus and
cervical sympathetic nerves (stellate ganglion, go
here).
This is accompanied by
(1) severe pain in the shoulder region
radiating toward the axilla and scapula along the
ulnar aspect of the muscles of the hand,
(2) atrophy of hand and arm muscles,
(3) Horner syndrome (ptosis, miosis,
hemianhidrosis, enophthalmos), and
(4) compression of the blood vessels with
edema.
Silvestri GA, et al. Chest, 2013

57. Chest MRI
MRI of the chest should not be performed
routinely for staging of the mediastinum.
MRI is useful in patients with NSCLC when
there is concern about involvement of the
superior sulcus or the brachial plexus.
Silvestri GA, et al. Chest, 2013

58. Mediastinoscopy
“…involves an incision just above the
suprasternal notch, insertion of a
mediastinoscope alongside the trachea,
and biopsy of mediastinal nodes.”
Silvestri GA, et al. Chest, 2013
Morbidity: 2%
Mortality: 0.08%

59. 2R
4R
7
2L
4L
1
3a
Mediastinoscopy
Node groups that cannot undergo a
biopsy with this technique include:
Posterior subcarinal (station 7)
Inferior mediastinal (stations 8, 9),
Aortopulmonary window (APW) (station 5)
Anterior mediastinal (station 6) nodes.

60. Mediastinoscopy
“…involves an incision just above the
suprasternal notch, insertion of a
mediastinoscope alongside the trachea,
and biopsy of mediastinal nodes.”
Silvestri GA, et al. Chest, 2013

61. Mediastinoscopy
“…involves an incision just above the
suprasternal notch, insertion of a
mediastinoscope alongside the trachea,
and biopsy of mediastinal nodes.”
Silvestri GA, et al. Chest, 2013
Sens Spec PPV NPV

62. Video Assisted Mediastinoscopy
“…A videomediastinoscope allows better visualization, more extensive
sampling (including posterior station 7)…”
Silvestri GA, et al. Chest, 2013

63. 63
Mediastinal Staging with Mediastinoscopy
Sensitivity
PPV
Specificity
NPV
78%
(100%)
(100%)
91%
89%
(100%)
(100%)
92%
Mediastinoscopy VAM

64. 6
5
The problem of
LN stations 5 and
6
Very significant for LUL tumors

66. 66
Mediastinal Staging with Anterior Mediastinoscopy and
Extended Cervical Mediastinoscopy
Sensitivity
PPV
Specificity
NPV
71%
(100%)
(100%)
91%
71%
(100%)
(100%)
91%
Anterior Extended Cervical
PPV

67. Video-Assisted Thoracic Surgery
“This is performed under general
anesthesia and, in general, is limited
to an assessment of only one side of
the mediastinum.
Access to the R-sided nodes is
straightforward, but access to the L
paratracheal nodes is more difficult”
Silvestri GA, et al. Chest, 2013
Morbidity: 2%
Mortality: 0%

68. 68
Mediastinal Staging with VATS
Sensitivity
PPV
Specificity
NPV
71%
(100%)
(100%)
91%
71%
(100%)
(100%)
91%
PPV

69. 69
Mediastinal Staging with VATS
Sensitivity
PPVSpecificity
NPV
PPV
99%
(100%)
(100%)
96%

70. Trans-
bronchial
Needle
Aspiration
Silvestri GA, et al. Chest, 2013

71. Trans-
bronchial
Needle
Aspiration
Silvestri GA, et al. Chest, 2013
Used mostly to corroborate
tumor involvement in enlarged
LN

72. Trans-
bronchial
Needle
Aspiration
Silvestri GA, et al. Chest, 2013
Used mostly to corroborate
tumor involvement in enlarged
LN

73. 73
Mediastinal Staging with Transbronchial Needle Aspiration
Sensitivity
PPVSpecificity
NPV
PPV
78%
(100%)
(100%)
77%

74. 74
Mediastinal Staging with Transbronchial Needle Aspiration
Sensitivity
PPVSpecificity
NPV
PPV
78%
(100%)
(100%)
77%
Corroboration strategy

75. EUS-NA
9R 9L
8R
8L
7
4L
5
Used mostly to corroborate tumor involvement in enlarged LN in EUS-reachable LN stations

76. EUS-NA
Silvestri GA, et al. Chest, 2013
Used mostly to corroborate tumor
involvement in enlarged LN in EUS-
reachable LN stations

77. EUS-NA
Silvestri GA, et al. Chest, 2013
Sens NPV

78. 78
Mediastinal Staging with EUS-NA
Sensitivity
PPVSpecificity
NPV
PPV
89%
(100%)
(100%)
86%

79. 79
Mediastinal Staging with EUS-NA
Sensitivity
PPVSpecificity
NPV
PPV
89%
(100%)
(100%)
86%
Corroboration strategy

80. EBUS-NA
Used mostly to corroborate tumor involvement in enlarged LN

81. EBUS-NA
Silvestri GA, et al. Chest, 2013

82. EBUS-NA
Silvestri GA, et al. Chest, 2013
Sens NPV

83. 83
Mediastinal Staging with EBUS-NA
Sensitivity
PPVSpecificity
NPV
PPV
89%
(100%)
(100%)
91%

84. Combined EUS-NA and EBUS-NA

85. 85
Mediastinal Staging with Combined EUS-NA and EBUS-NA
Sensitivity
PPVSpecificity
NPV
PPV
91%
(100%)
(100%)
96%

86. Putting it all together

87. Mediastinal staging strategies in NSCLC
Test Confirmatory Sensitivity (%) Specificity (%) PPV (%) NPV (%)
Chest CT 55 81 58 83
CT (-) in cI 85-95
MSCT-multicrit. 94-100 98.5 94 98.5-100
PET-CT 80 88 75 91
PET(-) in per. cI 96
Cervical med. 78 100 100 91
Video A. med. 89 100 100 92
Anterior med. + 71 100 100 91
Ext. cervical med. + 71 100 100 91
VATS +/- 99 100 100 96
TBNA + 78 100 100 77
EUS-NA + 89 100 100 86
EBUS-NA + 89 100 100 91
EUS & EBUS +/- 91 100 100 96
CT: Computed tomography, cI: clinical stage I, MSCT: Multi-slice computed tomography, PET: positron emission tomography; per. cI: peripheral clinical stage I; med: mediastinos copy,
A: assisted; Ext: extended; VATS: Video-assisted thoracic surgery; TBNA: Transbronchial needle aspiration biopsy; EUS: Endoscopic (esophageal) ultrasound; EBUS: endobronchial
ultrasound; NA: needle aspiration biopsy

88. Mediastinal staging strategies in NSCLC
Test Confirmatory Sensitivity (%) Specificity (%) PPV (%) NPV (%)
Chest CT 55 81 58 83
CT (-) in cI 85-95
MSCT-multicrit. 94-100 98.5 94 98.5-100
PET-CT 80 88 75 91
PET(-) in per. cI 96
Cervical med. 78 100 100 91
Video A. med. 89 100 100 92
Anterior med. + 71 100 100 91
Ext. cervical med. + 71 100 100 91
VATS +/- 99 100 100 96
TBNA + 78 100 100 77
EUS-NA + 89 100 100 86
EBUS-NA + 89 100 100 91
EUS & EBUS +/- 91 100 100 96
CT: Computed tomography, cI: clinical stage I, MSCT: Multi-slice computed tomography, PET: positron emission tomography; per. cI: peripheral clinical stage I; med: mediastinos copy,
A: assisted; Ext: extended; VATS: Video-assisted thoracic surgery; TBNA: Transbronchial needle aspiration biopsy; EUS: Endoscopic (esophageal) ultrasound; EBUS: endobronchial
ultrasound; NA: needle aspiration biopsy

89. Direct comparisons

90. 90
Minimally Invasive Endoscopic Staging of
Suspected Lung Cancer
TB-NA
PPV
EUS-NA
EUS-NA & EBUS-NA
EBUS-NA
Wallace MB, JAMA, 2008
36%
69%
69%
93%
78%
88%)
88%
97%
Sensitivity NPV
138 consecutive non(obviously) metastatic NSCLC underwent all three procedures

91. 91
Minimally Invasive Endoscopic Staging of
Suspected Lung Cancer
TB-NA
PPV
EUS-NA
EUS-NA & EBUS-NA
EBUS-NA
Wallace MB, JAMA, 2008
36%
69%
69%
93%
78%
88%)
88%
97%
Sensitivity NPV
138 consecutive non(obviously) metastatic NSCLC underwent all three procedures

92. 92
Endobronchial ultrasound versus mediastinoscopy for mediastinal
nodal staging of non-small-cell lung cancer
Sensitivity
PPV
Specificity
NPV
Accuracy
Um SW, JTO, 2015
88%
93%
100%
85%
81%
89%)
100%
78%
EBUS-TBNA Mediastinoscopy
138 consecutive NSCLC with cN1-cN3
*
*
*
* p < 0.005

93. 93
Endobronchial ultrasound versus mediastinoscopy for mediastinal
nodal staging of non-small-cell lung cancer
Sensitivity
PPV
Specificity
NPV
Accuracy
Um SW, JTO, 2015
88%
93%
100%
85%
81%
89%)
100%
78%
EBUS-TBNA Mediastinoscopy
138 consecutive NSCLC with cN1-cN3
*
*
*
* p < 0.005

94. 94
EBUS-centred versus EUS-centred mediastinal
staging in lung cancer: a randomized controlled
trial
Group A (EBUS-NA then EUS-NA)
PPV
EBUS after EUS improves accuracy and sensitivity. Therefore,
EBUS-FNA should be first
Kang HJ, Thorax, 2014
92%
86%
93%
97%
Accuracy post 1st test - Sensitivity Accuracy post 2nd test - Sensitivity
160 patients with histologically confirmed or strongly suspected potentially operable NSCLC
Group B (EUS-NA then EBUS-NA)
82%
60%
85%
92%

95. 95
P O S I T I O N S T A T E M E N T
My practice take…

96. 96
Known or suspected NSCLC
Contrast-Enhanced Chest CT (+liver & adrenal)
Negative / borderline positive Chest CT, clinical stage I/II
FDG PET-CT
VATS or EBUS/EUS-NA
Massive N2/N3 disease on
Chest CT
No further mediastinal
work-up
PET-CT(-) and
peripheral cI
No further mediastinal
work-up
PET-CT(+)
Tissue confirmation
required
PET-CT(-)
Context-based strategy

97. @onconerd