1. Lung cancer staging in 2011: use of pet Scan and other modalities
Nicole Bouchard MD FRCPC
Pulmonologist
April 29, 2011

2. Disclosure
I cannot identify any potential conflict of interest.

3. Objectives
1) Select the appropriate diagnostic tests to accurately stage lung cancer
2) Understand the strengths and weaknesses of PET Scan for lung cancer staging
3) Propose a rational approach to optimally stage mediastinal lymph nodes

4. TNM
Lababede O, Chest 2011; 139:

5. Diagnostic tests CT scan: PET-CT: Pulmonary function testing
chest and upper abdomen
PET-CT:
if a radical treatment is considered
Pulmonary function testing
Imaging of the head (MRI):
if symptoms
for small cell lung cancer
maybe in stage 3 disease NSCLC
Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27
Alberts WM, Chest 2007; 132; 1S-19S

6. Diagnostic tests Bone scintigraphy? PET is more sensitive
to avoid an unnecessary PET-CT
PET: from base of skull to upper thighs

7. Diagnostic tests
Least invasive approach that provides both the diagnostic and the stage
bronchoscopy, transthoracic CT guided needle biopsy, radial probe EBUS
EBUS, EUS, mediastinoscopy, VATS
US guided needle aspiration: thoracentesis, cervical lymph node, liver
EUS: left adrenal metastasis

8. Diagnostic tests → Adequate sample
IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma
NSCLC are to be classified into adenocarcinoma or squamous cell carcinoma
gefitinib, pemetrexed, bevacizumab
Travis WD, Journal of Thoracic Oncology 2011; 6:

9. Diagnostic tests Wait times and costs 2852 patients
provincial cancer registry: Manitoba
≥ 25% of patients waited more than 55 days
Cheung WY, Lung Cancer Sep [ Epub ahead of print ]

10. Diagnostic tests Multidisciplinary team
1222 patients with NSCLC,
survival?
prior
after
complete staging
79%
93%
multidisciplinary evaluation prior to surgery
62%
96%
adherence to guidelines
81%
97%
mean days from diagnosis to treatment
29 days
17 days
Freeman RK, Eur J Cardiothoracic Surg 2010; 38: 1-5

11. PET-CT Scan Preoperative PET-CT prospective, randomized study
189 patients, NSCLC
conventional staging (CT of the abdomen, bronchoscopy) or conventional staging plus PET-CT
PET-CT: reduced the number of futile thoracotomies, had no effect on survival
Fischer B, NEJM 2009; 361: 32-39

12. PET-CT Scan Preoperative PET-CT prospective, randomized trial
337 patients, stage 1-3A
NSCLC
PET-CT or conventional
(abdominal CT & bone scan)
cranial imaging
PET-CT: spares more patients from inappropriate surgery, but also incorrectly upstaged disease
Maziak DE, Ann Intern Med 2009; 151:

13. PET-CT Scan T stage (SUVmax 2,5)
false positive: infectious and inflammatory lesions
false negative: carcinoid, certain adenocarcinomas, uncontrolled diabetes, cavity with necrotic center, lesion < 8 mm
Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

14. PET-CT Scan
Solitary pulmonary nodule ( mm) and an initial SUVmax  2.6
retrospective study, CHUS, PET-CT
20 / 65 (31%) patients: diagnosis of cancer; mostly adenocarcinomas
risk factors for malignancy: higher 18F-FDG uptake, spiculated nodule
SUVmax  1: new threshold?
Houle MA, Can Respir J 2010; 17, suppl B: 6B

15. PET-CT Scan N stage CT > 10 mm in short axis diameter
sensitivity 57-61%, specificity 79-82%
PET
sensitivity 84%, specificity 89%
false negative: small volume, low metabolic activity
false positive: inflammation → sampling
size of the lymph node is important
Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27
Alberts WM, Chest 2007; 132; 1S-19S

16. PET-CT Scan M stage sensitivity 93%, specificity 96%
detect metastases:
15%, more with advanced stage
Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

17. PET-CT Scan Sample of any isolated distant lesion 350 patients
21% had a solitary lesion: 46% had a benign lesion or another cancer (second cancer or recurrence)
Lardinois D, J Clin Oncol 2005; 23:

18. Mediastinal lymph nodes (LN)
No lymph node sampling if uptake is within normal limits on PET-CT and < 1 cm
false negative rate: 5-7% for a peripheral tumor
if central tumor, N1 enlargement?
N2 or N3 ≥ 1 cm but PET negative?
Lymph node sampling if PET uptake is positive, to avoid false positive results
EBUS/EUS; +/- mediastinoscopy if negative

19. Mediastinal lymph nodes (LN)
EBUS: 2, 4, 7, 10, 11
EUS: 2L, 4L, 7, 8, 9
mediastinoscopy: 2R, 4R, anterior part of 7
Goldstraw P, IASLC Staging Manual in Thoracic Oncology, 2009

20. EBUS: meta-analysis (1)
Study caracteristics
Adams K, Thorax 2009; 64:

21. EBUS: meta-analysis (1)
Study results

22. EBUS: meta-analysis (1)
Sensitivity 88%
Specificity 100%

23. EBUS: meta-analysis (2)
Sensitivity 93%
Specificity 100%
Only 2 complications
2 / 1299 patients (0,15%)
pneumothorax
patient with COPD: hypoxemia during the procedure
Gu P, European Journal of Cancer 2009; 45:

24. EBUS: false negative rate
False negative rates
20-25%
External validity
other studies have been published

25. EBUS: learning curve Learning curves 500 patients 5 EBUS operators
no learning from
prior experience
operators 3 & 5: still
in the learning phase
after 100 procedures
Kemp SV, Thorax 2010; 65:

26. EBUS: cost effectiveness
cost-beneficial in comparison with surgical mediastinoscopy, for a prevalence as low as 30%
negative results confirmed by mediastinoscopy: cost-beneficial according to the prevalence of LN metastases (>79%)
Steinfort D, J Thorac Oncol 2010; 5:

27. EBUS: how many aspirations?
650 aspirations (163 MLN stations) in 102 patients, ROSE not available
best diagnostic value: 3 aspirations
(sensitivity: 69.8%, 83.7%, 95.3%, 95.3%)
2 aspirations: when at least one tissue core
Lee H, Chest 2008; 134:

28. EBUS: which needle? 21-gauge versus 22-gauge aspiration needle
45 lesions
same diagnostic yield
21G: better histological preservation but more blood contamination
Nakajima T, Respirology 2010 Sep [ Epub ahead of print ]

29. EBUS: mutations and SCLC
Mutation analysis
EGFR and KRAS mutations can be performed in cytologic specimens (EUS/EBUS)
also EML4-ALK fusion gene
SCLC: high diagnostic yield
Schuurbiers OC, J Thorac Oncol 2010: 5:
Nakajima T, J Thorac Oncol 2011; 6:
Wada H, Ann Thorac Surg 2010; 90:

30. EUS: meta-analysis 18 studies
No major complications; minor complications: 10 cases (0.8%),
Sensitivity
Specificity
18 studies
83%
97%
8 studies (abnormal MLN
on CT scans)
90%
4 studies (no abnormal MLN on CT scans)
58% -
Micames CG, Chest 2007; 131:

31. TBNA, EBUS, EUS 138 consecutive patients
known or suspected lung cancer on CT
Sensitivity
Negative predictive
value
Blind TBNA
36%
(15/42)
78%
(96/123)
EUS-FNA
69%
(29/42)
88%
(96/109)
EBUS-FNA
EUS-FNA + EBUS-FNA
93%
(39/42)
97%
(96/99)
Wallace MB, JAMA 2008; 299:

32. EBUS & EUS: single scope
139 consecutive patients, enlarged LN (CT)
EBUS & EUS: single linear US bronchoscope by one operator
Number of nodes sampled
Sensitivity
Specificity
Negative predictive value
EUS
229 (37%)
63 (89%)
100%
82%
EBUS
390 (63%)
65 (91%)
92%
Combined
619 (100%)
68 (96%)
96%
Herth FJ, Chest 2010: 138:

33. EBUS & EUS: single scope
150 potentially operable patients, prospective study
EBUS +/- EUS used for MLN inaccessible or difficult to access by EBUS
2 false negative (by mediastinoscopy)
Sensitivity
Specificity
Negative predictive value
Accuracy
EBUS
84% (38/45)
100%
93%
95%
EBUS + EUS
91% (41/45)
96%
97%
p value
0.332 -
0.379
0.360
Hwangbo B, Chest 2010; 138:

34. EBUS versus mediastinoscopy
66 patients, prospective crossover trial
Prevalence of malignancy: 89%
Diagnostic yield
EBUS: 91% versus mediastinoscopy: 78% (p=0.007)
disagreement: subcarinal lymph nodes (24%; p=0.011)
no difference: true pathologic N stage (per patient)
Ernst A, Journal of Thoracic Oncology 2008; 3;

35. ASTER study Randomized controlled multicenter trial 241 patients
Lung or mediastinal abnormality on CT, no extrathoracic metastases
EUS & EBUS (systematic sampling) and surgical staging if negative or surgical staging (mediastinoscopy): N2 & N3
Annema JT, JAMA 2010; 304:

36. ASTER study Nodal metastases Thoracotomy unnecessary
62 patients by combined staging (p=0.02)
41 patients by surgical staging
mediastinoscopy: 11 patients to identify 1 with nodal metastasis
Thoracotomy unnecessary
21patients in the mediastinoscopy group
9 patients in the combined group (p = 0.02)
No increase rate of complications

37. Conclusion PET-CT: before surgery and radiotherapy
When N2 or N3 is suspected on PET: EBUS; mediastinoscopy if negative
Complete mediastinal staging: EBUS +/- EUS; role of mediastinoscopy?
Further studies are ongoing
preoperative EBUS, EBUS vs mediastinoscopy, surgical staging vs endosonography