Dr. Laureano Molins

Cirurgia Toràcica

Hospital Clínic, Hospital Sagrat Cor, Barcelona

19 de gener de 2011

SCCT

CRIBATGE DEL CÀNCER DE PULMÓ: RESULTATS

BIBLIOTECA

BIBLIOTECA

CA Cancer J Clin 2009; 59:225-249

5 year Survival

Lung 14%

Colon 64%

Breast 89%

Prostate 99%

BIBLIOTECA

1963 1989 – 95 2009

Colon 43 62* 65

Breast 63 85* 85

Prostate 50 92* 93

Lung 8 14 16

(* = p<0.05)

5 YEAR CANCER SURVIVAL (MAYO CLINIC)

BIBLIOTECA

Non Small Cell Lung Cancer Surgery

• 1st cause of mortality from cancer

• Tobaco related in 90-95%

• Complete surgical resection is best chance

for cure

• 25% are “early stage” and potentially curable

BIBLIOTECA

0

10

20

30

40

50

60

70

80

90

100

Stage 1a

Stage 1b

Stage 2a

Stage 2b

Stage 3a

Stage 3b

Stage 4

5 Year

Survival Rate

Non Small Cell Lung Cancer

Cure Rate by Stage BIBLIOTECA

0

10

20

30

40

50

60

70

Percent

Stage

IA IB IIA IIB IIIA IIIB IV

LUNG CANCER SURVIVAL

Mountain CF. Chest 1997; 111: 1710-7

BIBLIOTECA

0

200

400

600

800

1000

1200

1400

1600

IA IB IIA IIB IIIA IIIB IV

Stage

Mountain CF. Chest 1997; 111: 1710-7

LUNG CANCER PRESENTATION

BIBLIOTECA

GCCB-S4,24 cm.

¡We want to change!

BIBLIOTECA

Prevention

Treatment

Early detection

LUNG CA BIBLIOTECA

Rationale for Screening Seems Intuitive

Overall 5-year survival 12%

Stage I 5-year survival 60-70%

% Stage I 14%

BIBLIOTECA

• HYPOTHESIS

• Find more cancers

• Find them earlier

• Increase chance of resectability

• Increase cure rate

Lung CancerScreening

BIBLIOTECA

• Non-Randomized Uncontrolled

(1950)

• Philadelphia Pulmonary Neoplasm

Research Project

• Veterans Administration Trial

• Tokyo Metropolitan Government Study

• South London Lung Cancer Study

• 20,000 pts. – No Benefit from

Screening CXR

Prior Screening Trials BIBLIOTECA

• Non-Randomized Controlled (1959-

1972)

• North London Cancer Trial

• Erfurt County Study

• Both showed

↑ % early cancers

↑ Resectability

↑ Survival rates

• No reduction in lung cancer mortality

Prior Screening Trials BIBLIOTECA

• Randomized Controlled (1970’s)

• Johns Hopkins Lung Project

• Memorial Sloan-Kettering Lung Project

• Mayo Lung Project

• Czechoslovakian Study

• 37,000 people enrolled

• Extensive analysis

Prior Screening Trials BIBLIOTECA

Johns Hopkins Annual CXR vs. Annual CXR

Memorial-Sloan +

Kettering Sputum Cytology

(q 4 mos)

Mayo Lung Project CXR + Sputum vs. Recommendation

Cytology (q 4 mos) of annual

assessment

Screening: The NCI Trials BIBLIOTECA

Years After Diagnosis

Survival

(%)

Mayo Lung ProjectIncidence Lung Cancer Survival

BIBLIOTECA

• Randomized Controlled (1970’s)

Better resectability in screened lung ca.

Better 5y survival in screened patients

No reduction in global mortality

CxR and sputum cytology not recommended as screening

Prior Screening Trials BIBLIOTECA

U.S. Preventive Services Task Force Grades and Recommendations

for Lung cancer Screening (1996)

Grade D Recommendation

The USPSTF recommends against routinely

providing (the service) to asymptomatic persons.

The USPSTF found at least fair evidence that (the

service) is ineffective or that harms outweigh the

benefits.

U.S. Preventive Services Task Force*, Ann intern Med 2004; 140:738-739.

BIBLIOTECA

DUPLICATION TIME BIBLIOTECA

SIZE / PROGNOSIS

PATZ, EF. et al. Chest 2000; 117: 1568-71

68%T2

82%T1

81%2,3 – 3,0

87%1,6 – 2,3

85%0,9 – 1,6Duke Univ.

80%0,2– 0,9510PATZ, EF et al.

Superv. 5 a.CmPacAUTOR

BIBLIOTECA

Author Pat. Cm 5y surv-

NARUKE T. (Jpn) 975 0 - 1 85%

1 - 2 85%

2 - 3 77%

NARUKE T. et al. Ann Thorac Surg 2001; 71: 1759-64

SIZE / PROGNOSIS BIBLIOTECA

GCCB-S. Eur Resp J 1999; 14: 812-6

63%T1 - T2 No1205

41%> 7

58%4,1 – 7

67%2,1 – 4GCCB-S

78%0,1 – 22361López Encuent A

2y surv.CmPatAUTHOR

SIZE / PROGNOSIS BIBLIOTECA

Deaths / N MST 5-Year

pT1, <=2cm 492/ 1816 NR 77%

pT1, >2-3 cm 582/ 1653 113 71%

pT2, <=5 cm 1311/ 2822 81 58%

pT2, >5-7 cm 461/ 825 56 49%

pT2, > 7 cm 240/ 364 29 35%

pT3 338/ 619 36 41%

0%

20%

40%

60%

80%

100%

0 5 10 15Years After Surgery

Survival by tumor size in patients with

pT1-T3 pN0 R0 TNM 7th Edition BIBLIOTECA

CT Screening Trials

• Japanese Trials

• I-ELCAP

• NELSON

(Dutch/Belgian)

• Mayo Clinic Lung

Screening Project

What About High-Tech Machines?

BIBLIOTECA

• Kaneko M et al, Radiology 1996; 201:798-802

• Sone et al, Lancet 1998; 351:1242-45

KANEKO

(1996)

SONE (1998)

Patients 1369 5483

Lung Ca. diagnosed 15 (0,3%) 19(0,48%)

No view at CxR 11 15

SCREENING - CT BIBLIOTECA

3 radiologists, 2 pneumologists, 1 thoracic surgeon, 1 oncologist, 1 epidemiologist

• 1,000 smokers > 65 years of age.

• Baseline and annual LDCT

• Work up algorithm – growth of NCN

ELCAPEarly Lung Cancer Action Program

Henschke et al., Lancet, 1999;354:99

BIBLIOTECA

1.000 persons: >60 y. y >10 paq/year (46% f)

Non calcified detected nodules: 363

(23% of patients)

Nodules confirmed as LC: 27 (7,4%)

SCREENING – Cornell Univ. ELCAP

1 nodul 159

2-3 nodules 59

4-6 nodules 46

Biger nodule <5 mm 58%

Henschke CI et al, Lancet 1999; 354: 99-105

BIBLIOTECA

CA. PULMÓN: ACTITUD ANTE LOS HALLAZGOS DEL CRIBAJE

1.000 Initial; 363 nodules in 233 patients (23%)28 Biopsies 27 Malignant (12%)

1 Benign

1.184 Repeated: 30 new nodules (2,5%) 16 persist after 1 month (1,4%)8 Biopsies 7 Malignant (44%)

1 Benign

2/36 Benign biopsies 5,5% + 3 non recomended biopsies Benign

Henschke CI et al. NY Acad Science 2001; 952: 124-34

ELCAP / BIOPSIES FOLLOWING PROTOCOL

BIBLIOTECA

Abril 2009 Mayo 2010 Nov 2010

Henschke CI et al. NY Acad Science 2001; 952: 124-34

SCREENING ELCAP / MALIGNANT NODULES

27 BASELINE: 15 mm

18 Adenocarcinoma4 Adenosquam3 Bronchoalveolar1 Squamous1 Atipical Carcinoid

22 IA1 IB1 IIB3 IIIA

7 REPEAT: 7 mm

6 Adenocarcinoma

1 Small Cell Ca

6 IA 86%

1 IIIA

85%

BIBLIOTECA

1.520 persons >50y and 20 paq/year (48% female)

Non calcified detected noduls: 1.358 in 782 patients

(51% of patients)

Noduls confirmed as LC: 17 (1,2%) (13 mm)

SCREENING – MAYO CLINIC

< 4 mm 39 %

4-7 mm. 50 %

8-20 mm. 10 %

>21 mm. 1 %

Swensen S et al.Am J Respir Crit Care Med 2002; 165: 508-13

BIBLIOTECA

Indeterminate

Nodule on Initial CT

< 3 mm

Thin section CT (1-3 mm

collimation) at 6 months

Benign Indeterminate

Follow-up CT in 6 months, if stable, follow with annual scan

Mayo CT Screening Trial

Nodule Management Algorithm BIBLIOTECA

Indeterminate

Nodule on Initial CT

4 -7 mm

Thin section CT (1-3 mm

collimation) at 3 months

Benign Indeterminate

Follow-up CT at 3 months, if stable, again in 3 months

Mayo CT Screening Trial

Nodule Management Algorithm BIBLIOTECA

Indeterminate Nodule

on Initial CT

8-20 mm

Thin section CT Now

Benign Indeterminate

Nodule enhancement

study (CT, PET)

>21 mm

Biopsy or

removal

>15HU <15 HU: CT

in 3 months

Mayo CT Screening Trial

Nodule Management Algorithm BIBLIOTECA

Low-dose CT Screening Studies

NCC-

Japan

Mayo Munster ELCAP Shinshu

Smoking

hx (pk yr)

20 20 20 10 NS

Age 50 50 40 60 40

Subjects 1369 1520 919 1000 5483

L.C. (%) 15 (0.43) 15 (1) 13 (1.4) 27 (2.7) 19 (0.35)

Stage I 93% 80% 62% 85% 87%

BIBLIOTECA

Grade B recommendation

The USPSTF concludes that the evidence is

insufficient to recommend for or against screening

asymptomatic persons for lung cancer with either

low dose CT or CXR, sputum cytology or a

combination of these tests.

U.S. Preventive Services Task Force*, Ann intern Med 2004; 140:738-739.

U.S. Preventive Services Task Force

Recommendations for Lung Cancer

Screening(2004) BIBLIOTECA

• International consortium – 40+ centers

• USA, Europe, Asia

• Annual screening with LDCT

• Started in 2000 - 50.000 participants

I-ELCAP BIBLIOTECA

• 28,689 participants

• 464 diagnosis of cancer

• 436 NSCLC

• Relationship between size and stage

Arch Int Med 2006; 166: 321-325

I-ELCAP Results I BIBLIOTECA

15mm 16-25 mm 26-35 mm 36 mm

Total 258 118 40 20

% N0M0 91% * 83% * 68% * 55%

NSCLC - 436

Arch Int Med 2006; 166: 321-325

I-ELCAP Results I BIBLIOTECA

• Screening is a process, not a single test

• Baseline: 13% have a positive result

• Annual: 5% have a positive result

Low-dose

CT

Positive

result

Work-up

algorithm

Diagnosis of

lung cancer

I-ELCAP

Regimen of screening BIBLIOTECA

• 31.567 baseline screenings

• 4.186 positive (13%)

• 405 cancer (1,3%)

• 5 interval cancer

• 27.456 annual

screenings

• 1.460 positive (5%)

• 74 cancer (0,3%)

• 0 interval cancer

N Engl J Med 2006;355:1763-71

484 cancer

412 Stage I (85%)

I-ELCAP Results II BIBLIOTECA

• Biopsies: 92% positive for lung cancer

• Surgical mortality: 0,5%

• Pathology panel (revision of 375 cancers)

• 356 (95%) showed signs of invasion (pleural,

basal membrane, vascular, bronchial)

N Engl J Med 2006;355:1763-71

I-ELCAP Results II BIBLIOTECA

BIBLIOTECA

10-year Kaplan-Meier survival

All cases 484 431 354 279 181 90 50 28 16 9 2

Resected Stage I 300 279 241 191 119 59 34 18 12 7 1

Resected clinical Stage I: 92% (95% CI: 88%-95%)

All cases: 80% (95% CI: 74%-85%)

No. at risk

BIBLIOTECA

1. Real influence of detection of smaller tumors

2. “Overdiagnosis” (tumors that do not affect the patient´s life)

3. “Healthy patients”

4. Cost-efective?; Cost of a life saved?

BIBLIOTECA

PROBLEMS WITH SCREENING

Stage I Lung Cancers: With and Without Treatment

Number 5-yr

Survivors

Rate

•Unresected 114 9 8%

•MSKCC 5 0 0%

•JH 29 1 3%

•Mayo: 11 1 9%

•Japan 69 7 10%

BIBLIOTECA

Years After Diagnosis

Survival

(%)

Mayo Lung ProjectIncidence Lung Cancer Survival

BIBLIOTECA

Resection of potentially curable lung ca.

Minimize resection of benign nodules.

LUNG CA SCREENINGOBJECTIVES

BIBLIOTECA

Broncoscopy

F. N. A.

Videothoracoscopy

Thoracotomy

NODULE BIOPSY BIBLIOTECA

< 2 (cm) 2 - 4(cm) > 4 (cm)

Fletcher 2% 40% 63%

Wallace 11% 43%

Cortese 11% 64%

Hanson 11% 62%

BRONCOSCOPY BIBLIOTECA

F.N.A. BIBLIOTECA

Small nodules: CT guided biopsy

8 mm POSITIVE NSCLC

European randomized trials comparing

CT to no screening.

• Netherlands-Belgium (NELSON)(4 centers): 15.822 2003-2009.

• Denmark (DLCST)(Copenhagen): 4.104. 2004-2010

• Germany (LUSI)(Heidelberg): 4.000. 2007-2014

• Italy (ITALUNG)(4 centers); 3.000. 2004-2010

BIBLIOTECA

Management of Lung Nodules Detected

by Volume CT Scanning

CONCLUSIONS: Among subjects at high risk for lung cancer who

were screened, the chances of finding lung cancer 1 and 2 years

after a negative first-round test were 1 in 1000 and 3 in 1000,

respectively.

First round: 2.6% of the participants had a positive test result.

Second round: 1.8% of the participants had positive test result

Round one: Sensitivity: 94.6% (95% confidence interval [CI], 86.5 to 98.0)

Negative predictive value 99.9% (95% CI, 99.9 to 100.0).

In the 7.361 subjects with a negative screening result in round one, 20 lung

cancers were detected after 2 years of follow-up.

NELSON STUDY: 7.557 participants underwent CT screening in

years 1, 2, and 4 of a randomized trial of lung-cancer screening.

N Engl J Med 2009;361:2221-9.

BIBLIOTECA

National Lung Screening Trial

(NLST)

• Accrual complete

• Follow-up 4-5 years

• Result expected in 2010

• 90% power for 20% reduction in LCSM

53,000 current/former (10y)

smoker (>30p/y) 55-74 yrs old

( / )

Annual CT x3 CxR x3

BIBLIOTECA

NLST (4 nov, 2010)

• Se detiene prematuramente el estudio tras análisis

preliminar:

• Mortalidad en grupo TC había disminuido ya un 20.3%

con respecto al grupo control: 354 vs 442.

• Mortalidad por cualquier causa había disminuido un

7% (25% por LC; otras: Enf. Cardiovascular)

• Todos los participantes notificados con indicación de

hablar con MF:

• A los del grupo control para considerar TC de cribado.

• A los del grupo TC para considerar continuar con TC.

• Pendiente de publicación

BIBLIOTECA

NY-ELCAP

• Tasa de mortalidad CV con el grado de

calcificación.

• CAC 0: 1.2%

• CAC 1-3: 1,8%

• CAC 4-6: 5,0%

• CAC 7-12: 5,3%

• CAC >4:*OR 2.1 (IC 95% 1.4-3.1,

p=0.0002) Radiology 2010 257:541-548

PROGRAMA DE DESHABITUACIÓ TABÀQUICA I

PROJECTE DE CRIBATGE PER AL DIAGNOSTIC PRECOÇ

DEL CÀNCER DE PULMÓ (CP)

Proposta BIBLIOTECA

10-year Kaplan-Meier survival

All cases 484 431 354 279 181 90 50 28 16 9 2

Resected Stage I 300 279 241 191 119 59 34 18 12 7 1

Resected clinical Stage I: 92% (95% CI: 88%-95%)

All cases: 80% (95% CI: 74%-85%)

No. at risk

BIBLIOTECA

MOLTES GRÀCIES PER

L’ATENCIÓ!

* Ajustado a sexo, edad, paquetes-años

Radiology 2010 257:548

BIBLIOTECA