Medical School of Oncology
Highlights on NSCLC Management
STAGING STRATEGIES
Maria Grazia Ghi
Divisione di Oncologia-Venezia
Roma, 29 ottobre 2010
Il nuovo sistema di stadiazione TNM Il nuovo sistema di stadiazione TNM definisce il nodulo polmonare in altro definisce il nodulo polmonare in altro
lobo ipsi-laterale come:lobo ipsi-laterale come:
1.1. T3T32.2. T4T43.3. M1M1
1 / 30 Cross-tab label
100%
0% 0%
1 2 3
Qual è la metodica di stadiazione in uso Qual è la metodica di stadiazione in uso nel vostro Centro per la stadiazione del nel vostro Centro per la stadiazione del
mediastino con sospetto N2?mediastino con sospetto N2?
1.1. TAC + PETTAC + PET
2.2. Imaging (TAC +/- PET) + Imaging (TAC +/- PET) +
TBNATBNA3.3. Imaging (TAC +/- PET) + Imaging (TAC +/- PET) +
EBUS/EUSEBUS/EUS4.4. Imaging (TAC +/- PET) + Imaging (TAC +/- PET) +
mediastinoscopiamediastinoscopia
1 / 30 Cross-tab label
10%
2100%
30%40%
TNM STAGING SISTEM
6TH EDITION- Different stages of disease based on anatomic extention and survival data
- Monoinstitutional database (USA)
- 5,319 patients from historical cases (pre-1975)
- Adopted from 1997 to December 2009
- No internal or external validation
TNM STAGING SISTEM
7TH EDITION- Different stages of disease based on anatomic extention and survival data
- International database from 4 continents (North America, EU, Asia, Australia)
- More than 67.000 patients of cases treated 1990-2000
- Adopted from January 2010
- Internal and external validation with recognized statistical methods
THE NEW STAGING SISTEM
The importance of staging
- Prognostic information
- Therapeutic decision :
surgery +/- induction therapy
chemoradiation
chemotherapy
c TNM stage : MST & 5y OS
THE NEW STAGING SISTEM
Changes for T definition
THE NEW STAGING SISTEM
Changes for T definition
- To subclassify T1 and T2 according to tumor size
- To identify a new T3 definition according to tumor size
- To reclassify additional node in the same lobe and in different ipsilateral lobe
- To reclassify malignant pleural effusion
THE NEW STAGING SISTEM
Changes for T definition
according to dimensional criteria
THE NEW STAGING SISTEM
Changes for T definition (T1-3)
according to dimensional criteria
OS for clinical T stage N0
THE NEW STAGING SISTEM
Changes for T definition (T1-3)
according to dimensional criteria
THE NEW STAGING SISTEM
Changes for T definition
according to other parameters
Reclassify T4 tumours due to additional tumour nodeles in the primary lobe as T3
Reclassify M1 tumours due to additional tumour nodeles in other ipsilateral lobe as T4
Reclassify T4 tumours due to malignant pleural effusion as M1, create M1a category
THE NEW STAGING SISTEM
Changes for T definition (T3-4)
according to other parameters
OS for clinical T stage N0
- multiple nodes in the same lobe is stage II
- multiple nodes in different lobe
on the same side is stage III
THE NEW STAGING SISTEM
Changes for T definition (T3-4)
according to other parameters
THE NEW STAGING SISTEM
Methods for T stage definition
- modern spiral contrast CT scan (mediastinal or lung windows)
Good quality multi-slice CT
is the minimum standard
THE NEW STAGING SISTEM
Difficulties for T stage definition
- visceral pleural invasion (T2)
- mediastinal pleural invasion (T3)
- parietal pericardial invasion (T3)
- hilar fat invasion (T2)
- mediastinal fat invasion (T4)
- ground glass opacities
THE NEW STAGING SISTEM
Changes for M definition
THE NEW STAGING SISTEM
Changes for M definition
- To identifie intrathoracic and extrathoracic metastases (M1a vs M1b)
- To reclassify additional node in the controlateral lung (M1a)
- To reclassify malignant pleural effusion (M1a)
THE NEW STAGING SISTEM
Changes for M definition
OS for clinical M stage
THE NEW STAGING SISTEM
Changes for M definition
No Mx definition!
THE NEW STAGING SISTEM
Methods for M stage definition
- contrast CT scan (chest and abdominal)
- brain MRI/CT scan in symptomatic pts
- Bone scan if sympthoms
- PET or PET/CT scan
THE NEW STAGING SISTEM
N definition
THE NEW STAGING SISTEM
the importance of N definition
- Diagnosis of NSCLC is often based on nodes analysis
- Adequate tissue sampling need for biological and molecular analysis
THE NEW STAGING SISTEM
The importance of N definition
- Mediastinal lymphnode involvement is the most important prognostic factor in M0 pts
- Mediastinal lymphnode involvement influences therapeutic strategies
- If complete resection is considered, an accurate mediastinal lymphnode evaluation is mandatory
THE NEW STAGING SISTEM
Changes for N definition
- New defined nodal zone and nodal
station map
- No changes for N definition
THE NEW STAGING SISTEM
No changes for N definition
THE NEW STAGING SISTEM
No changes for N definition
OS for c N stage any cT,M0
but .....
should it be changed?
c N2
Stage T2b N2 M0 – IIIa
- Different therapeutic approach ?
- Different prognosis?
Andre F et al, JCO 2000
Surgery could cure a small proportion of N2 patients
Distinguishing mN2 from cN2 must be a goal of preoperative
Surgery could cure a small proportion of N2 patients
Distinguishing mN2 from cN2 must be a goal of preoperative
• Minimal N2 (mN2): no preoperative evidence of gross N2 at CT scan
• Clinical N2 (cN2):
evidence of N2 disease at CT scan
N2 single station (N2 L1)
• N2 multiple station (N2L2)
• LN size
Grunenwald d et al, JNCI 1997
Ruckdeshel JC, Semin Oncol 1997
Subclassification of N2 disease(not validated)
THE NEW STAGING SISTEM
No changes for N definition
Unanswered questions
- Different prognosis based on the n°of node?
Probably yes but too small n° of patients
5y OS: single N1: 48%
multiple N1: 35% p<0.09
single N2: 34%
multiple N2: 20% p<0.001
N3 zone
N2 zone
Nodal zone and nodal station mapsolving discrepancies between
Western and Japanase map
N1 zone
N2 zone
THE NEW STAGING SISTEM
Nodal zone and nodal station map
METHODS FOR N STAGE DEFINITION
- CT scan
- PET or PET/CT scan
- mediastinoscopy
- thoracoscopy
- TTNA
- TBNA
- EBUS TBNA
- EUS FNA
Not invasive
Minimally invasive
Invasive
Not invasive methods
- CT scan
- PET scan
- PET-CT
MEDIASTINAL LN STAGING
CT scan
- based on node size
- sensitivity 57%
- specificity 82%
- PPV 56%
- NPV 83%
- Clinical applicability limited for small nodes
(20% may contain metastases)
- Large nodes may be benign
- Insufficient for clinical decision
- Usefull for select procedures for sampling of suspected LNs
De Leyn et al, E J CT S 2007
METHODS FOR N STAGE DEFINITION
PET scan
Functional imaging
- Sensitivity 74%
- Specificity 85%
- PPV 79%
- NPV 93%
- Insufficient anatomic details
- Limitation in spacial resolution
- Uptake by inflammatory disease
De Leyn et al, E J CT S 2007
METHODS FOR N STAGE DEFINITION
PET-CT scan
- Dual purpose:
. Node size
. Biologic activity
- Sensitivity 89%
- Specificity 84-94%
METHODS FOR N STAGE DEFINITION
METHODS FOR N STAGE DEFINITION
Invasive surgical methods
- mediastinoscopy (cervical)
- left side videothoracoscopy (VATS) for tumor of the left upper lobe (station 5 and 6)
- anterior mediastinotomy (Chamberlain procedures) – higher morbidity than cervical approach
METHODS FOR N STAGE DEFINITION
Invasive methods
METHODS FOR N STAGE DEFINITION
Cervical Mediastinoscopy - General anesthesia
- LN station 1,2,4, 7 sub.
- Sensitivity 78%
- Specificity 100%
- False negative 10%
- False positive 0%
- Morbidity 2%
- Mortality 0.08%
- Poorly utilized (27%)
- some stations are not accessible
(5,6,8,9,7 posterior)
- No consensus on how many LN station should be examined (at least one omolateral, one controlateral
and the subcarinal)
METHODS FOR N STAGE DEFINITION
Detterbeck et al, Chest 2007
Minimally invasive methods
- Transbronchial needle aspiration - TBNA
(blind)
- Trans thoracic needle aspiration - TTNA
(CT or fluoroscopic guided)
- EBUS TBNA
- EUS FNA
METHODS FOR N STAGE DEFINITION
EBUS FNA for mediastinal staging
- No general anesthesia
- Anterior LN station
2,4, 7, 10, 11
- station 3 (post)
- Sensitivity 76-93%
- Specificity 100%
- False positive 0%
- False negative 20%
METHODS FOR N STAGE DEFINITION
EBUS metanalysis for mediastinal staging 1299 pts from 11 studies (CT or PET pos. in 8 studies)
METHODS FOR N STAGE DEFINITION
EUS FNA for mediastinal staging - No general anesthesia
- posterior LN station 2,4, 5(AP w) ,7
- inferior LN station 8,9
- Sensitivity 84%
- Specificity 99.5%
- False positive 0.7%
- False negative 19%
METHODS FOR N STAGE DEFINITION
Detterbeck et al, Chest 2007
EUS metanalysis for mediastinal staging 1201 pts from 18 studies
METHODS FOR N STAGE DEFINITION
Micames et al, Chest 2007
EBUS vs EUS
- 160 pts with enlarged CT nodes
- all pts received EUS and EBUS nodes staging
METHODS FOR N STAGE DEFINITION
TBNA vs EUS vs EBUS vs EBUS+EUS
Wallace et al, JAMA 2008
138 pts regardless of radiographic LN disease
METHODS FOR N STAGE DEFINITION
ASTER RANDOMIZED STUDY
Endosonography (EBUS + EUS)
followed by surgical staging
vs
surgical staging alone
in N2-3 suspect disease
Tournoy et al, ASCO 2010
ASTER RANDOMIZED STUDY
ASTER RANDOMIZED STUDY
ASTER RANDOMIZED STUDY
ASTER RANDOMIZED STUDY
ASTER RANDOMIZED STUDY
ASTER RANDOMIZED STUDY
CONCLUSION OF ASTER STUDY
IMPLICATIONs:
- Initial endosonography should be the
new standard for mediastinal staging
- Starting mediastinal staging with endosonography in resectable NSCLC:
1) improved the detection of LN metastases
2) reduces futile thoracotomies
3) for a similar complication rate
as compared to surgical staging alone
- High false negative value for blind TBNA (around 30%) and CT scan (around 20%); high false positive for PET (around 20%)
- Endoscopy ultrasonography improve the accuracy of TBNA (but expertise dependent)
- Endoscopy ultrasonography associated with minimal complications
- Minimally invasive techniques (high specificity but low NPV) are complementary to mediastinoscopy
METHODS FOR N STAGE DEFINITION
THE NEW STAGING SISTEM
International gudelines for N definition
- AIOM
- ESMO
- ASCO
- NCCN
- ACCP
NORMAL CT MEDIASTINUMN1 or central lesion
(independent from PET scan)
EUS-NA or EBUS- TBNA
NEGATIVE
MEDIASTINOSCOPY
CT STAGE I-IIIbSUITABLE FOR SURGERY
PET SCANfor medastinal staging
NEGATIVE POSITIVE
SURGERY MEDIASTINALLN SAMPLING
2007
(first choice)
CT N2-3 M0(independent from PET scan)
Tissue confIrmation
EUS-NA or EBUS- TBNA (first choice)
POSITIVE NEGATIVE
MEDIASTINOSCOPY
MULTIMODALITY TREATMENT
POSNEG
SURGERY
2007
THE NEW STAGING SISTEM
Limiting of TNM staging
- No hystologic type differences
- No clinical status differences
- Limited/No biological information
CONCLUSIONS 1
-Staging is a multidisciplinary process involving imaging, medical and surgery techniques
- Accurate pretreatment staging is crucial for an adequate treatment plan
- Changes in the new TNM edition mainly involved T size stratification, multiple nodes and pleural effusion
CONCLUSIONS 2
- Mediastinoscopy is the first choice in patients with suspected N1 and for central tumor with normal radiographic mediastinum
- In patients with suspected N2-3 disease tissue confirmation with ultrasound biopsy is indicated (first choice). Mediastinoscopy is of second choice after negative ultrasound biopsy
- Combined EUS/EBUS could replace mediastinoscopy in the future
Il nuovo sistema di stadiazione TNM Il nuovo sistema di stadiazione TNM definisce il nodulo polmonare in altro definisce il nodulo polmonare in altro
lobo ipsi-laterale come:lobo ipsi-laterale come:
1.1. T3T32.2. T4T43.3. M1M1
1 / 30 Cross-tab label
100%
0% 0%
1 2 3
Qual è la metodica di stadiazione Qual è la metodica di stadiazione suggerita come prima scelta per la suggerita come prima scelta per la
stadiazione del mediastino con sospetto stadiazione del mediastino con sospetto N2?N2?
1.1. TAC + PET + TBNATAC + PET + TBNA
2.2. TAC + PET + EBUS/EUSTAC + PET + EBUS/EUS
3.3. TAC + PET + TAC + PET +
mediastinoscopiamediastinoscopia
1 / 30 Cross-tab label
10%
2100%
30%