Screening for Lung Cancer Michael S. Nolledo, MD Deborah Heart and Lung Center 1 1
Outline Ø Introduction Ø Lung Cancer Screening pre-2010 Ø Lung Cancer Screening today 2 2
Lung Cancer 2011 (Siegel et al., CA 2011) Ø 221,130 estimated new cases in 2011 (14% of all cancers) l 2 nd most common in males and females Ø 156,940 deaths estimated in 2011 (27% of all cancer deaths) l Number 1 killer in males and females Ø More people die of lung cancer than of colon, breast, and prostate cancers combined. 3 3
Lung Cancer and Smoking 4 4
Lung Cancer and Smoking 5 5
Lung Cancer Stage at Diagnosis (SEER 2001-2007) Stage Distribution and 5-year Relative Survival by Stage at Diagnosis for 2001-2007, All Races, Both Sexes Stage at Diagnosis Localized (confined to primary site) Regional (spread to regional lymphnodes) Distant (cancer has metastasized) Stage Distribution (%) 15 52.0 22 24.2 56 3.6 Unknown (unstaged) 7 8.1 5-year Relative Survival (%) 6 6
Lung Cancer Treatment (Spira et al., NEJM 2004) 7 7
Four Chemotherapy Regimens for Advanced Non Small-Cell Lung Cancer (Schiller et al., NEJM 2002) 8 8
Screening for Breast Cancer (Fletcher et al., NEJM 2003) 9 9
CXR Screening 1 (Manser et al., Thorax 2003) 10 10
CXR Screening 2 (Manser et al., Thorax 2003) 11 11
CXR Screening 3 (Manser et al., Thorax 2003) 12 12
Early Lung Cancer Action Project (ELCAP) (Henschke et al., NEJM 2006) 13 13
ELCAP Patients (Henschke et al., NEJM 2006) 14 14
ELCAP Lung Cancer Diagnoses (Henschke et al., NEJM 2006) 15 15
ELCAP Survival Curves (Henschke et al., NEJM 2006) 16 16
ELCAP Conclusions (Henschke et al, NEJM 2006) Ø Annual Spiral CT Screening can detect lung cancer that is curable. Ø Detection rates for screening for lung cancer slightly higher than rates for breast cancer detection on screening mammograms. Ø CT Screening is highly cost effective. 17 17
Problem with ELCAP (NY Times 2008) Small print at the end of the study, published in the New England Journal of Medicine, noted that it had been financed in part by a little-known charity called the Foundation for Lung Cancer: Early Detection, Prevention & Treatment. A review of tax records by The New York Times shows that the foundation was underwritten almost entirely by $3.6 million in grants from the parent company of the Liggett Group, maker of Liggett Select, Eve, Grand Prix, Quest and Pyramid cigarette brands. 18 18
Computed Tomography Screening and Lung Cancer Outcomes (Bach et al., JAMA 2007) 19 19
JAMA Study Results (Bach et al., JAMA 2007) 20 20
JAMA Study Conclusion (Bach et al., JAMA 2007) Screening for lung cancer with low-dose CT may increase the rate of lung cancer diagnosis and treatment, but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. Until more conclusive data are available, asymptomatic individuals should not be screened outside of clinical research studies that have a reasonable likelihood of further clarifying the potential benefits and risks. 21 21
Lead Time Bias (Cancer.gov) 22 22
Length Bias (Cancer.gov) Length Bias Screening Indolent Cancer Begins Symptoms & Dx Death Detectable Preclinical Phase Aggressive Cancer Begins Sx & Dx Death Screening tends to detect more indolent cancers 23 23
The National Lung Screening Trial Research Team Ø Lung Cancer Screening Trial sponsored by: l l l National Cancer Institute American College of Radiology Imaging Network Lung Screening Study Group Ø Prospective Randomized Trial from 2002-2007 involving 53,454 patients at 33 different medical institutions. Total research cost ~ $200M. 24 24
NLST Eligibility Criteria (NLST Research Team NEJM 2011) Ø Included: 55-74 years of age with 30 pack years smoking; if former smoker, quit within past 15 years. Ø Excluded: l l l l Previous diagnosis of lung cancer Had Chest CT within the past 18 months Had hemoptysis Had unexplained weight loss of 15 lbs. 25 25
NSLT Patient Characteristics (NLST Research Team NEJM 2011) 26 26
NSLT Screening Results (NLST Research Team NEJM 2011) 27 27
NSLT Diagnostic Evaluation (NLST Research Team NEJM 2011) 28 28
NSLT Diagnostic Evaluation Complications (NLST Research Team NEJM 2011) 29 29
NSLT Stage and Histology of Lung Cancers Detected (NLST Research Team NEJM 2011) 30 30
NSLT Mortality Results (NLST Research Team NEJM 2011) Ø Relative reduction in the rate of death from lung cancer with low dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P = 0.004). Ø Significant reduction with low-dose CT screening of 6.7% (95% CI, 1.2 to 13.6) in the rate of death from any cause (P = 0.02). Ø Number needed to screen with low-dose CT to prevent one death from lung cancer was 320. 31 31
NSLT Limitations Ø Healthy-volunteer effect. Ø Scanners that are currently used are technologically more advanced than those that were used in the trial. Ø NLST was conducted at a variety of medical institutions, many of which are recognized for their expertise in radiology and in the diagnosis and treatment of cancer. Ø No estimate of risk reduction with ongoing screening. 32 32
NSLT Questions Ø Will populations with risk profiles that are different from those of the NLST participants benefit? Ø Are less frequent screening regimens equally effective? Ø For how long should screening continue? Ø Would the use of different criteria for a positive screening result, such as a larger nodule diameter, still result in a benefit? Ø What are the cost implications? 33 33
My 2 Cents Ø Cost per year of life saved: l Colorectal Cancer Screening - $11,890-$29,725 l Breast Cancer Screening - $36,924 l Pap Smear Screening - $5,392 l Lung Cancer Screening - $90,000 Ø Cost per year of life saved with smoking cessation intervention: $3,500 34 34