Medical School of Oncology Highlights on NSCLC Management STAGING STRATEGIES Maria Grazia Ghi Divisione di Oncologia-Venezia Roma, 29 ottobre 2010

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

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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


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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


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



according to dimensional criteria


Changes for T definition (T1-3)


OS for clinical T stage N0






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




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





Methods for T stage definition

- modern spiral contrast CT scan (mediastinal or lung windows)

Good quality multi-slice CT

is the minimum standard


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


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)



OS for clinical M stage



No Mx definition!


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


N definition


the importance of N definition

- Diagnosis of NSCLC is often based on nodes analysis

- Adequate tissue sampling need for biological and molecular analysis


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


Changes for N definition

- New defined nodal zone and nodal

station map

- No changes for N definition


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)



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


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


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


PET-CT scan

- Dual purpose:

. Node size

. Biologic activity

- Sensitivity 89%

- Specificity 84-94%



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


Invasive methods


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)


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


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%



EBUS metanalysis for mediastinal staging 1299 pts from 11 studies (CT or PET pos. in 8 studies)


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%



Detterbeck et al, Chest 2007

EUS metanalysis for mediastinal staging 1201 pts from 18 studies


Micames et al, Chest 2007

EBUS vs EUS

- 160 pts with enlarged CT nodes

- all pts received EUS and EBUS nodes staging


TBNA vs EUS vs EBUS vs EBUS+EUS

Wallace et al, JAMA 2008

138 pts regardless of radiographic LN disease


ASTER RANDOMIZED STUDY

Endosonography (EBUS + EUS)

followed by surgical staging

vs

surgical staging alone

in N2-3 suspect disease

Tournoy et al, ASCO 2010







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



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


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


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


10%

2100%

30%

Documents

Medical School of Oncology Highlights on NSCLC Management STAGING STRATEGIES Maria Grazia Ghi Divisione di Oncologia-Venezia Roma, 29 ottobre 2010