Non Small Cell Lung Cancer

IntroductionMira Wollner

RAMBAM MEDICAL CENTER

Epidemiology

Most frequent cause of cancer diagnosed in the US – about 12% of all cancer

NSCLC represents ~ 80% of lung cancer In year 2004 ~ 173,770 new cases and 160,440 deaths Leading cause of cancer deaths in both men ( 32%) and

women (25%) 75% of new cases present with non resectable disease Overall 5 year survival < 15%

American Cancer Society, Cancer Facts & Figures 2005

SEER Cancer Statistics, 1998-2002. http://seer.cancer.gov

Newly Diagnosed NSCLC in Israel

1999 = 1338

2002 = 1450

Etiology

Cigarette smoking responsible for > 80% cases Use of filter Tar content Variation of tobacco blends Contains ~ 300 chemicals and up to 40 potent

carcinogens (nitrate) Recent changes in histological dominant type (due to changes in tobacco blend and use of filter)

American Cancer Society, Cancer Facts & Figures 2005SEER Cancer Statistics, 1998-2002. http://seer.cancer.gov

Histology Adenocarcinoma ( 45%)

Atypical Alveolar Hyperplasia ( precursor) Broncho-alveolar carcinoma Squamous cell carcinoma ( 33%) Large cell carcinoma ( 9% ) Adenosquamous carcinoma Pleomorphic carcinoma Carcinoma of salivary gland Carcinoid

American Cancer Society, Cancer Facts & Figures 2005

SEER Cancer Statistics, 1998-2002. http://seer.cancer.gov

Diagnosis

Medical history Physical exam Labs Imaging studies

CXR CT-scan PET-CT scan Bone scan

Diagnosis

Bronchoscopy (FOB) Mediastinoscopy Histology

Sputum FNA (cytology/biopsy) thoracotomy

Methods of Spread

Vascular channels Lymphatic channels Airborne or lymphatic (satellite nodules) Lymphatic spread to regional lymph nodes:

bronchopulmonary (segmental and lobar (N1), mediastinal (N2-3) ,supraclavicular (N3)

Retrograde lymphatic spread (pleural surface) Direct invasion Systemic dissemination

TNM stage groupingTNM stage grouping

Stage 0Stage 0 TisTis NONO MOMO

Stage IStage I T1T1 NONO MOMO

T2T2 NONO MOMO

Stage IIStage II T1T1 N1N1 MOMO

T2T2 N1N1 MOMO

Stage III AStage III A T1T1 N2N2 MOMO

T2T2 N2N2 MOMO

T3T3 NONO MOMO

T3T3 N1N1 MOMO

T3T3 N2N2 MOMO

Stage III BStage III B Any TAny T N3N3 MOMO

T4T4 Any NAny N MOMO

Stage IVStage IV Any TAny T Any NAny N M1M1

Stage I diseaseStage I disease

>> 2 cm 2 cm

OROR

OROR

N0: No lymph node involvement

No lobarNo lobarbronchusbronchusinvolvementinvolvement

T T 3 cm 3 cm

T1 N0 M0 T2 N0 M0

T T 3 cm3 cm

T + visceral pleuraT + visceral pleurainvolvedinvolved

T + atelectasisT + atelectasis

Stage II disease Stage II disease

>> 2 cm 2 cm

OROR

OROR

N1: Intrapulmonary and/or hilar nodes involved

No lobarNo lobarbronchusbronchusinvolvementinvolvement

T T 3 cm 3 cm

T1 N1 M0 T2 N1 M0

T T 3 cm3 cm

T + visceral pleuraT + visceral pleurainvolvedinvolved

T + atelectasisT + atelectasis

Stage IIIA diseaseStage IIIA disease

< 2 cm< 2 cm >> 2 cm 2 cm

T2OROR

OROR

OROR

OROR

T1T1

N1: peribronchial or ipsilateral hilarN1: peribronchial or ipsilateral hilar

T T 3 cm 3 cm

No lobarNo lobarbronchus involvementbronchus involvement

T T mediastinal mediastinal pleurapleura (or pericardium)(or pericardium)

T T chest wall chest wall (or diaphragm)(or diaphragm)

T3 N0 M0T3 N1 M0T3 N2 M0

T1 N2 M0T2 N2 M0

T T 3 cm 3 cm

T + visceral pleuraT + visceral pleurainvolvedinvolved

T + atelectasisT + atelectasis

N2: ipsilateral mediastinal and subcarinalN2: ipsilateral mediastinal and subcarinal

Stage IIIB diseaseStage IIIB disease

Any T, N3, M0Any T, N3, M0 Any N, T4, M0Any N, T4, M0

ScaleneScaleneSupraclavicularSupraclavicular

N3: lymph nodes involvedN3: lymph nodes involved T4: mediastinal involvementT4: mediastinal involvement

Any TAny T

Any NAny N

T4T4

Mediastinal lymph node map Mountain CF, Dresler CM. Chest 1997; 111:1718-1723

Involvement of lymphatic metastatic spread in non-small cell lung cancer accordingly to the primary cancer location

Skip metastases to level 10 (hilar) ~ 5% Skip metastases to mediastinal LN ~ 19% Mediastinal LN dissection must be the standard procedure

Kotoulas CS et al 2004 Lung Cancer;44:183-191

Patterns of failure after resection of NSCLC

CHRIS R. KELSEY,., KIM L. LIGHT, AND LAWRENCE B. MARKS, 2006Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 4, pp. 1097–1105

Treatment algorithmGlotocan, Epidemiology Lung Cancer, 2002

NSCLC Diagnosis

Resectable I – II – IIIA

28%

Locally advancedIIIA

Unresectable IIIB33%

Unresectable IIIBMetastatic IV

39%

Surgery(RT)

Adjuvant CT

Combined Chemo-radiotherapy

1st line chemotherapy

Consolidation

Survival and FrequencyMountain Chest 1997; 111:1718-1723

Stage Frequency (%) 5-year survival %

Clinical Pathological

IA ~ 10 61 67

IB 38 57

IIA ~ 13 34 55

IIB 24 39

IIIA ~ 22 13 25

IIIB ~ 22 ~ 5

IV ~ 32 <1

Surgery

Lobectomy = gold standard for early stage

Limited recection showed higher local recurrence rate (15%) then lobectomies (5%) for T1N0 tumors

Ginsberg RJ et al. Ann Thorac Surg 1995;60:615

Sites of Recurrence Following Complete Surgical Resection

Mountain CF, McMurtrey MJ, Frazier OH. Current results of surgical treatment for lung cancer. Cancer Bull 1980;32:105–108

Resected LN-negative FailureAuthor Stage Pts No Chest % Distant %

Feld et all T1N0 162 9 17

T2N0 196 11 30

Pairolero et all

T1N0 170 6 15

T2N0 158 6 23

Thomas et all

T1N0 Sq 226 5 7

T1N0

non-Sq

346 9 17

Resected LN-positive FailureAuthor Stage Pts No Chest % Distant %

Feld et all T1N1 32 9 22

Pairolero et all

T1N1 18 28 39

Martini et all T1-2N1sq 93 16 31

T1-2N1

adeno114 8 54

T2-3N2sq 46 13 52

T2-3N2 adeno

103 17 61

Completely Resected Stage II or IIIA With Postoperative Adjuvant Therapy (ECOG)

Keller SM, Adak S, Wagner H, Herscovic A, et al. New Engl J Med 2000,343;17:1217-1222

Completely Resected Stage II or IIIA With Postoperative Adjuvant Therapy (continuing)

Keller SM, Adak S, Wagner H, Herscovic A, et al. New Engl J Med 2000,343;17:1217-1222

Patterns of Failure

S. Lee et al. Postoperative adjuvant chemotherapy and radiotherapy for stage II and III non-small cell lung cancer (NSCLC) Lung Cancer 37 (2002) 65/71

Prognostic Factors

S. Lee et al. Postoperative adjuvant chemotherapy and radiotherapy for stage II and III non-small cell lung cancer (NSCLC) Lung Cancer 37 (2002) 65/71

Are All T1-2 Tumors the Same?Mulligan CR et al. Ann Thorac Surg 2006;81(1):220-226

Tumor size (cm) 5 year survival (%)

≤1 48,6

1-2 45,9

2-3 25,6

3-4 27

4-5 14,4

>5 11,6

Outcome After Surgical Resection in Operable NSCLC

Pisters and Le Chevalier. J Clin Oncol 2005;23:3270-3278

Stage

5 year survival

(%)

Relapse

(%)

Local Distant

IA T1N0M0 67 10 15

IB T2N0M0 57 10 30

IIA T1N1M0 55

IIB T2N1M0 39 12 40

T3N0M0 38

IIIA T3N1M0 25 15 60

T1N2M0 23

Prognostic factors TNM Stage Tumor size Pathological N2

Extend of LN involvement (single vs multiple) Occult vs Bulky

Type of surgery wedge/segmentectomy vs lobectomy LN sampling vs dissection

Positive surgical margins age > 60 years PS/QoL