Nicole Bouchard MD FRCPC

Pulmonologist

April 29, 2011

Disclosure

I cannot identify any potential conflict of interest.

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

TNM

Lababede O, Chest 2011; 139: 183-189

Diagnostic tests

CT scan:chest and upper abdomen

PET-CT: if a radical treatment is considered

Pulmonary function testing Imaging of the head (MRI):

if symptomsfor small cell lung cancer maybe in stage 3 disease NSCLC

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27Alberts WM, Chest 2007; 132; 1S-19S

Diagnostic tests

Bone scintigraphy? PET is more sensitiveto avoid an unnecessary PET-CTPET: from base of skull to upper thighs

Diagnostic tests

Least invasive approach that provides both the diagnostic and the stagebronchoscopy, 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

Diagnostic tests

→ Adequate sample

IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma

NSCLC are to be classified into adenocarcinoma or squamous cell carcinomagefitinib, pemetrexed, bevacizumab

Travis WD, Journal of Thoracic Oncology 2011; 6: 244-285

Diagnostic tests

Wait times and costs2852 patientsprovincial cancer registry: Manitoba≥ 25% of patients waited more than 55 days

Cheung WY, Lung Cancer 2010 Sep [ Epub ahead of print ]

Diagnostic tests

Multidisciplinary team1222 patients with NSCLC, 2001-2007

survival?

Freeman RK, Eur J Cardiothoracic Surg 2010; 38: 1-5

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

PET-CT Scan

Preoperative PET-CTprospective, randomized

study189 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

PET-CT Scan

Preoperative PET-CTprospective, randomized trial337 patients, stage 1-3A

NSCLCPET-CT or conventional

(abdominal CT & bone scan)cranial imagingPET-CT: spares more patients from

inappropriate surgery, but also incorrectly upstaged disease

Maziak DE, Ann Intern Med 2009; 151: 221-228

PET-CT Scan

T stage (SUVmax 2,5)false positive: infectious and inflammatory

lesionsfalse negative: carcinoid, certain

adenocarcinomas, uncontrolled diabetes, cavity with necrotic center, lesion < 8 mm

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

PET-CT Scan

Solitary pulmonary nodule (8 - 30 mm) and an initial SUVmax 2.6 retrospective study, CHUS, PET-CT20 / 65 (31%) patients: diagnosis of cancer;

mostly adenocarcinomasrisk factors for malignancy: higher 18F-FDG

uptake, spiculated noduleSUVmax 1: new threshold?

Houle MA, Can Respir J 2010; 17, suppl B: 6B

PET-CT Scan

N stageCT

> 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

Alberts WM, Chest 2007; 132; 1S-19SLim E, Thorax 2010; 65 (Suppl III); iii1-iii27

PET-CT Scan

M stagesensitivity 93%, specificity 96%detect metastases:

15%, more with advanced stage

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

PET-CT Scan

Sample of any isolated distant lesion350 patients21% had a solitary lesion: 46% had a benign

lesion or another cancer (second cancer or recurrence)

Lardinois D, J Clin Oncol 2005; 23: 6846-6853

Mediastinal lymph nodes (LN)

No lymph node sampling if uptake is within normal limits on PET-CT and < 1 cmfalse 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 resultsEBUS/EUS; +/- mediastinoscopy if negative

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

EBUS: meta-analysis (1)

Study caracteristics

Adams K, Thorax 2009; 64: 757-762

EBUS: meta-analysis (1)

Study results

EBUS: meta-analysis (1)

Sensitivity 88% Specificity 100%

EBUS: meta-analysis (2)

Sensitivity 93% Specificity 100% Only 2 complications

2 / 1299 patients (0,15%)pneumothoraxpatient with COPD: hypoxemia during the

procedureGu P, European Journal of Cancer 2009; 45: 1389-1396

EBUS: false negative rate

False negative rates20-25%

External validityother studies have been published

EBUS: learning curve

Learning curves500 patients5 EBUS operatorsno learning from

prior experience

operators 3 & 5: still

in the learning phase

after 100 procedures

Kemp SV, Thorax 2010; 65: 534-538

EBUS: cost effectiveness

Cost effectivenesscost-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: 1564-1570

EBUS: how many aspirations?

650 aspirations (163 MLN stations) in 102 patients, ROSE not availablebest 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: 368-374

EBUS: which needle?

21-gauge versus 22-gauge aspiration needle

45 lesionssame diagnostic yield21G: better histological preservation but

more blood contamination

Nakajima T, Respirology 2010 Sep [ Epub ahead of print ]

EBUS: mutations and SCLC

Mutation analysisEGFR 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: 1664-1667

Nakajima T, J Thorac Oncol 2011; 6: 203-206

Wada H, Ann Thorac Surg 2010; 90: 229-234

EUS: meta-analysis

18 studies

No major complications; minor complications: 10 cases (0.8%),

Micames CG, Chest 2007; 131: 539-548

Sensitivity Specificity

18 studies 83% 97%

8 studies (abnormal MLNon CT scans)

90% 97%

4 studies (no abnormal MLN on CT scans)

58% -

TBNA, EBUS, EUS

138 consecutive patients known or suspected lung cancer on CT

Wallace MB, JAMA 2008; 299: 540-546

Sensitivity Negative predictive

value

Blind TBNA 36% (15/42)

78%(96/123)

EUS-FNA 69%(29/42)

88%(96/109)

EBUS-FNA 69%(29/42)

88%(96/109)

EUS-FNA + EBUS-FNA 93%(39/42)

97%(96/99)

EBUS & EUS: single scope

139 consecutive patients, enlarged LN (CT) EBUS & EUS: single linear US bronchoscope

by one operator

Herth FJ, Chest 2010: 138: 790-794

Number of nodes

sampled

Sensitivity Specificity Negative predictive

value

EUS 229 (37%) 63 (89%) 100% 82%

EBUS 390 (63%) 65 (91%) 100% 92%

Combined 619 (100%) 68 (96%) 100% 96%

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)Hwangbo B, Chest 2010; 138: 795-802

Sensitivity Specificity Negative predictive

value

Accuracy

EBUS 84% (38/45) 100% 93% 95%

EBUS + EUS

91% (41/45) 100% 96% 97%

p value 0.332 - 0.379 0.360

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; 577-582

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: 2245-2252

ASTER study

Nodal metastases62 patients by combined staging (p=0.02)41 patients by surgical stagingmediastinoscopy: 11 patients to identify 1

with nodal metastasis

Thoracotomy unnecessary21patients in the mediastinoscopy group9 patients in the combined group (p = 0.02)

No increase rate of complications

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 ongoingpreoperative EBUS, EBUS vs mediastinoscopy,

surgical staging vs endosonography