You Smoke, You Get Lung Cancer, You Die: Can Screening Change this Paradigm? Robert J. McKenna M.D. Chief, Thoracic Surgery Cedars Sinai Medical Center AATS Saturday 4/28/2012
Cancer Screening Cancer Breast Prostate Colon lung Screening Test Mammography BRCA PSA Rectal exam Stool guaic Colonoscopy NONE
Detectable preclinical phase of disease Preclinical phase of disease Clinical phase Lead time A B Dx Cp S D Biologic onset of disease Disease detectable via screening Preclinical disease detected via Critical point Symptoms develop Death
Prevalence of Lung Cancer by Stage 18% IV? III I + II 18% 25% 39%
Prevalence of Stage 1 Lung Cancer Stage 1 In US 20% With CXR screening 40% With CT screening 80+%
Lung Cancer Screening: who to screen Ages 55 to 74 years 30-pack-year history of smoking
Lung Cancer Latency after Smoking Cessation N= 626 patients with lung cancer 11.3% current smokers 77% smoking history 59.8% stopped smoking 11-60 years earlier (39% 20+ years) Mung, McKenna, JCO 2011
45.0 40.0 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 0-10 years 40.2 11-20 years 21.2 21-30 years 16.1 31-40 years 10.7 9.7 41-50 years 51-60 years Length of Smoking Cessation at the time of Lung Cancer Diagnosis (years) 1.9 Former Smokers 39% 20+ years after smoking cessation
Lung Cancer Screening ELCAP 31,567 patients screened 27,4576 with follow up CT scans 484 lung cancers detected 412 (85%) stage 1 10 yr survival of resected lung cancers 88%
Lung Cancer Screening ELCAP 7 mm adenocarcinoma
ELCAP Recommendations for masses identified 5-14 mm: follow up CT scan in 3months >15 mm: biopsy + PET: biopsy -PET: CT in 3 months
Lung Cancer Screening ELCAP (NSCL) Size of tumors T1N0 <15 mm 91% 16 to 25 mm 83% 26 to 35 mm 68% >36 mm 55% Arch Intern Med. 2006;166:321-325
Lung Cancer Screening ELCAP (small cell) Size of tumors T1N0 < 25 mm 67% >25 mm 23% Arch Intern Med. 2006;166:321-325
Lung Cancer Screening 8 cancers detected and not resected 5 yr survival = 0 How does lead time bias explain that?
National Lung Screening Trial (ELCAP) 1 lung-cancer-related death prevented for every 320 high-risk individuals screened 200,000 deaths from lung cancer/ year Screening would save 40,000 lives
National Lung Screening Trial (NLST) 20% reduction in deaths from lung cancer among current and former heavy smokers screened with helical low-dose CT, compared with those screened with chest radiograph. N Engl J Med. 2011;365:395-409
National Lung Screening Trial (NLST) 53,454 patients screened Test # patients Positive test False positive CT 26,722 24.2% 96.4% CXR 26,732 6.9% 94.5% N Engl J Med. 2011;365:395-409
National Lung Screening Trial (NLST) 53,454 patients screened Test # patients Lung cancer Cancer deaths CT 26,722 645 247 CXR 26,732 572 309 N Engl J Med. 2011;365:395-409
Results NLST CT screening reduced lung cancer mortality by 20.0% (95% CI, 6.8 to 26.7; P=0.004) N Engl J Med. 2011;365:395-409
National Lung Screening Trial (NLST) Lung Cancer Deaths CXR 247 /100,000 Low dose CT 309/100,000 95% confidence interval, 6.8 to 26.7
National Lung Screening Trial (NLST) 96% of all nodules found by CT were not cancer "burden" of following up with patients with nodules is "not trivial" high-risk individuals consists of adults 55 to 74 years of age with a 30-pack-year or more history of smoking N Engl J Med. 2011;365:395-409
National Lung Screening Trial (Recommendations) Follow up CT depends on the size and status: Solid vs nonsolid vs part-solid ground-glass, ground-glass opacity PET with CT for nodules >8 mm Biopsy or excision of nodules that are suspicious for lung cancer, on PET /CT N Engl J Med. 2011;365:395-409
National Comprehensive Cancer Network (NCCN) Strongly recommend low-dose helical computed tomography (CT) screening for select individuals at high risk for lung cancer Journal of the National Comprehensive Cancer Network (2012;10:240-265)
Radiologic Management of Small Pulmonary Nodule Size (mm) 4 Nodules on CT (Fleischner Society Statement Radiology 2005; 237:395-400) Low-risk Patient No Follow-up > 4 6 Follow-up: 6 12 months > 6 8 Follow Follow-up: 6 12 mo. Then 18 24 12 months Follow High-risk Patient Follow-up 12 months Follow-up: 6 12 mo. Then: 18 24 mo. Follow-up: 3 6 mo. Then: 9 12 mo. Then: 24 mo. > 8 Follow Follow-up: 3, 9, 24 mos. PET/Dynamic CT and/or biopsy Same
Over-diagnosis Bias Renal cell cancer: 1% incidence by clinical and radiologic data; 60-80 years of age. 22% incidence at autopsy unrelated to death. Lung Cancer: 1% incidence at autopsy
ELCAP 2006 412 Clinical Stage I Lung 88% Estimated 10- year survival (Kaplan-Meier curves) 302 Stage I Lung resected within 1 mo after diagnosis 92% 10-year survival (Kaplan-Meier curves) 8 Stage I Lung Cancer without Rx All died within 5 years
Negative Effects of Screening Discovery of Pseudo-disease Radiation exposure Cost
Health Care Costs USA Total spending $2.3 trillion 2007 (16% of GDP) $7,500 / U.S. resident In 1970 U.S. spending $75 billion ($356 /U.S. resident Health Care Cost rising 2.4 % faster than the GDP since 1970
Cost of Imaging 5% ($12 billion) of total health care dollar 23% of Out-patient cost (largest component of out-patient health care) Fastest growing component of health care
Screening Financial Issues Cost & Benefit Breast and Colon Cancer: $30 50K/Life-year Saved
Environmental Radiation Exposure Rads/yr msv/year L.A. 0.1 1 Denver 0.3 3 Alps 2 20 Himalayas 13 130 Ave. Background (US) Airplane Travel 0.36 3.6 0.0007 Rad/hour 0.007 msv/hour Radiologist 5 50
Radiation Exposure Medical Entrance Dose Chest X-ray AP Lumbar 0.2 Spine Fluoroscopy 0.01 R/film 0.1 msv/film 0.2 2 2 R/minute 20 msv/m Mammogram (max California <0.2 R/film) Digital: 0.14 R/f; Analog: 0.15 R/f (< 2.0 msv/film) Dig: 1.4; Ana: 1.5 MDCT 0.3 1.0 3.0 10
Cancer Risk Secondary to Radiation Exposure in Diagnostic Radiology U.S. and Canada T.B. Sanitariums 1930-1950 1-2 min Fluoroscopy / exam Up to 100 rads/min 50 100 exams / yr 2000-5000 rads/ yr 250% increased incidence of breast cancer 60% increased breast cancer related deaths
Length-Time Bias CT Screening is most-sensitive for the detection of peripheral lung cancer. Most peripheral lung cancers are adenocarcinoma. Peripheral lung cancers are less likely to have positive lymph nodes.