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An Approach to Lung Cancer Screening
ALAN NG W K MBBS, M Med(Int Med), FAMS(Resp Med)
FRCP(Edin), FRCP(Lond), FACP
Respiratory & Critical Care Medicine
Tan Tock Seng Hospital [email protected] sg
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Doc, I’m worried about lung cancer….
• A 55 yr old manager who quit smoking 10 years ago comes in for a routine visit at the hypertension clinic. He previously smoked 10 cigarettes a day for 20 years. His medical history is otherwise unremarkable. He feels well and exercises regularly. A close friend of his was recently diagnosed with advanced lung cancer. He is worried about lung cancer and seeks your advice on screening.
• What would you tell him?
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The young smoker
• 33 yr old executive who smokes 30 cigarettes/day since age 20 yrs
• Wants to be screened so that any disease can be caught early and treated.
• Read about LDCT; wants it done.
• How would you advise him?
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NCI press release on NLST
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USA, 2013
American Cancer Society estimates for 2013
• 228,190 new cases of lung cancer
– 118,080 in men
– 110,110 in women
• 159,480 deaths from lung cancer
– 87,260 in men
– 72,220 in women
– 27% of all cancer deaths
Cancer Facts & Figures 2013, American Cancer Society
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Singapore Cancer Registry
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Lung Cancer in Singapore
Singapore Cancer Registry
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Lung Cancer
• Smoking is the biggest risk factor for lung cancer
• Smoking and lung cancer
– Age of initiation
– Duration of smoking
– Number of cigarettes smoked
– Depth of inhalation of smoke
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Lung Cancer
• Risk of developing lung cancer in current smokers is 10% – 15%
• Quitting smoking reduces risk of lung cancer
• Risk falls with every year remaining smoke free
• Former smokers have a higher risk than never smokers
• After 10 years, lung cancer risk is half of continuing smokers
• Over half of lung cancers are diagnosed in former smokers
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Lung Cancer
• 5 year survival rate : 15%
• Most lung cancers at advanced stage of disease at time of clinical presentation and diagnosis (40% stage 4, 30% stage 3)
• 16% of cancers diagnosed at Stage 1
• Survival related to stage at time of diagnosis
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Is there a case for lung cancer screening?
• Diagnosis of disease at early stage (asymptomatic)
• Curative resection possible
• Improved survival
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Principles of Screening (WHO)
• There should be an important health problem
• There should be an accepted treatment available
• There are facilities for diagnosis and treatment
• There should be a recognisable latent early stage
• A suitable test or examination is available
• Test should be acceptable for the population
• Natural history of the disease must be understood
• There is an agreed policy on treatment
• The cost of screening (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole
• Screening should be a continuing process and not a ‘once and for all’ project.
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Lung Cancer Screening
• There is no role for chest Xray in screening for lung cancer – Annual screening with chest Xray has NOT been shown to
reduce lung cancer mortality
– Practice of annual chest Xray (to look for lung tumour) is not recommended
• Emerging role of CT scan – Detection of smaller lesions (Chest Xrays unable to detect
85% of early stage lung cancers detected by CT scans)
– Low Dose Computed Tomography (LDCT)
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The first study to show that lung cancer screening may save lives
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National Lung Screening Trial (NSLT)
• 53, 454 subjects at high risk for lung cancer – Age 55 – 74 yrs – At least 30 pack years – Current smoker, or – Quit within last 15 years
• Randomly assigned to 3 annual screenings
– Low dose CT 26, 722 – Chest radiograph 26, 732
• Positive result
– Non-calcified nodule at least 4 mm diameter (LDCT) – Any non-calcified nodule or mass (CXR) – Other abnormalities (adenopathy, pleural effusion…)
• Cases of lung cancer detected • Deaths from lung cancer
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Positive results in NLST
• Substantially higher rate of positive screening tests in LDCT group
• > 90% of positive screening tests in first round of screening led to diagnostic evaluation
• 96.4% of positive results in LDCT group, and 94.5% of those in chest radiography group were false positive results
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New Engl J Med 2011; 365: 395-409
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Reduced Lung Cancer Mortality With Low-Dose Computed Tomographic Screening. N Engl J Med 2011; 365:395-409
National Lung Screening Trial results
LDCT detected more lung cancer than CXR (645 per 100,0000 person yrs compared to 572 per 100,000 person yrs for CXR
20% reduction in mortality from lung cancer observed in LDCT group as compared with CXR group (LDCT : 247 per 100,000 person yrs ; CXR : 309 per 100,000 person yrs) Rate of death from any cause was also reduced in the LDCT group as compared with CXR group by 6.7%.
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NLST : Lung Cancer Specific Mortality
• Deaths per 100,000 person years
– LDCT 247 deaths
– CXR 309 deaths
• LDCT reduced lung cancer mortality by 20%
• Number needed to screen with LDCT to prevent one death from lung cancer is 320
New Engl J Med 2011; 365: 395-409
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Low dose CT screening
• More sensitive in detecting small nodules
• More lung cancers diagnosed
• Early stage lung cancer
• Reduced mortality from lung cancer (20%)
• All-cause mortality reduced by 6.7%
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Adverse events/complications NLST
• Few and minor (screening examination)
• Complications after diagnostic evaluation low
• At least 1 complication
– LDCT group 1.4%
– CXR group 1.6%
• 16 patients in LDCT group died (10 had lung cancer), and 10 in radiography group died (all had lung cancer) within 60 days after an invasive procedure
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Endorsement of LDCT lung cancer screening
• National Comprehensive Cancer Network
• American Cancer Society
• American Society of Clinical Oncology
• American College of Chest Physicians
• United States Preventive Services Task Force
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Screen everybody? Who?
• Defining the population to be screened
• Managing the positive finding
• Limiting potential harm from screening
• Environment where screening is carried out
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Who to screen
• Patients at high risk of developing lung cancer from tobacco smoking :
– 55 to 74 years of age
– At least 30 pack years smoking history
– Either still smoking or have quit smoking within the last 15 years
NLST selection criteria
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American Cancer Society
• Does NOT recommend tests to screen for lung cancer in people who are at average risk
• Screening guidelines for subjects who are high risk of lung cancer due to cigarette smoking :
– 55 to 74 years of age
– In fairly good health
– At least 30 pack year smoking history AND either still smoking or have quit smoking within the last 15 years
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• Patients stratified into quintiles according to their predicted 5 year risk of death from lung cancer (lowest risk to highest risk group)
• Assessed – Efficacy – False positive results – Lung cancer deaths
N Engl J Med 2013: 369: 245-254
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N Engl J Med 2013: 369: 245-254
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Targeted screening to improve benefits
• Calculate prescreening risk of death from lung cancer
• Number of subjects to screen to prevent 1 death from lung cancer – Lowest risk 5276
– Highest risk 161
• Lower false positives in 20% at the highest risk
Targeting of low dose CT screening according to the risk of lung cancer death. Kovalchik S A et al. N Engl J Med 2013; 369: 245-54
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N Engl J Med 2013: 369: 245-254
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Management & Followup of nodule
• Many nodules will be detected at LDCT screen
• Determining which nodules to subject for further testing
– Size of nodule
– Characteristics of nodule
– Interval change
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NLST positive findings
• Positive results 24.2% of LDCT (23.3% false positive)
6.9% of chest radiographs (6.5% false positive)
• 96% were false positive
• 11% of false positive led to an invasive test
• Most positive results turn out to be false positive on further
evaluation.
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N Engl J Med 2013; 369: 910-919
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Probability of lung cancer
• Relationship between nodule size and cancer was nonlinear – 5 mm nodule 2 in 1000 – 10 mm nodule 2 in 100 – 20 mm nodule 1 in 10 – 4 fold increase in diameter associated with 50 X
increase in risk of lung cancer
• Nodule location in the upper lobes increased the probability of cancer
• Peri-fissural nodules present minimal risk of cancer
N Engl J Med 2013; 369: 910-919
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Potential harms of screening
• False negative & false positive results • Incidental findings
– Emphysema – Coronary artery calcifications
• Overdiagnosis • Radiation exposure
– 0.61 – 1.5 mSv per scan – Cumulative exposure
• Unnecessary lung biopsy and surgery • Psychological distress
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Lung cancer screening programme
• LDCT screening should be performed as programme in a center with the relevant expertise and experience, to evaluate and manage positive findings. – Diagnostic radiology
– Interventional radiology
– Pulmonology
– Thoracic surgery
– Oncology
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• Smoking cessation remains a high priority for current smokers
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American Cancer Society
• Does NOT recommend tests to screen for lung cancer in people who are at average risk
• Screening guidelines for subjects who are high risk of lung cancer due to cigarette smoking :
– 55 to 74 years of age
– In fairly good health
– At least 30 pack year smoking history AND either still smoking or have quit smoking within the last 15 years
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• Sufficient evidence to support screening provided the patient has undergone a thorough discussion of the benefits, limitations and risks, and can be screened in a setting with experience in lung cancer screening
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Limitations & Harms
• Screening does not detect all lung cancers
• Detection of cancer by LDCT does NOT mean death from lung cancer will be avoided
• Anxiety associated with abnormal test results, additional imaging, biopsy
• Investigation of incidental findings
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A reminder …..
• The single best way to prevent lung cancer deaths is to never start smoking, and if already smoking, to quit permanently.
• Smoking cessation counseling to all smokers undergoing screening
• Smokers should not use LDCT imaging as an excuse to continue smoking.
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Thank you for your attention