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 alan_ng_wk@ttsh.com sg

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?

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?

NCI press release on NLST

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

Singapore Cancer Registry

Lung Cancer in Singapore

Singapore Cancer Registry

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

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

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

Is there a case for lung cancer screening?

• Diagnosis of disease at early stage (asymptomatic)

• Curative resection possible

• Improved survival

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.

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)

The first study to show that lung cancer screening may save lives

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

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

New Engl J Med 2011; 365: 395-409

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%.

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

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%

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

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

Screen everybody? Who?

• Defining the population to be screened

• Managing the positive finding

• Limiting potential harm from screening

• Environment where screening is carried out

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

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

• 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

N Engl J Med 2013: 369: 245-254

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

N Engl J Med 2013: 369: 245-254

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

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.

N Engl J Med 2013; 369: 910-919

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

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

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

• Smoking cessation remains a high priority for current smokers

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

• 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

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

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.

Thank you for your attention