Lung Cancer—Protocol

Protocol: Screening for Lung Cancer
May 2014
ERSC Project Lead Investigator
Donna Fitzpatrick-Lewis
CTFPHC Working Group Chair
Gabriela Lewin
CTFPHC Working Group Members
Maria Bacchus, Neil Bell, Jim Dickinson, Harminder Singh
PHAC Scientific Research Manager
Lesley Dunfield

Section I. Purpose and background

This report will be used by the Canadian Task Force on Preventive Health Care (CTFPHC) to inform an update of its 2003 guidelines on screening adults for lung cancer.1 This systematic review synthesizes the benefits and harms of lung cancer screening in average and high risk asymptomatic adults and answers a number of contextual questions that consider issues including test properties and performance and participants’ preferences regarding screening for lung cancer.


Lung cancer is a form of cell malignancy that begins in the lungs. Non-small cell lung cancers [(NSCLC) e.g., adenocarcinoma, squamous cell carcinoma, or large cell carcinoma] are the most common sub-types of the disease; more rarely diagnosed are the faster-growing small cell lung cancers (e.g., small cell carcinoma, mixed small cell/large cell, or combined small cell carcinoma).23 This review deals primarily with the NSCLCs.

Prevalence and burden of lung cancer

Lung cancer is estimated to be the most commonly diagnosed form of cancer in Canada (estimated 25,500 new cases in 2013) as well as the main cause of cancer related mortality among Canadians (estimated 20,200 deaths attributed to lung cancer in 2013).4 Almost all (97%) of the estimated new cases of lung cancer in 2013 are expected to be identified in adults aged 50 years and older.4 For the same year, the age-standardized incidence rate of lung cancer in men is estimated at 60.1 cases per 100,000 compared with 46.8 cases per 100,000 in women.4 While the incidence rate is currently higher in men than women, the rate for men became stable about 30 years ago (approximately 20 years after a reduction in smoking prevalence among men) and has been showing a significant (P < 0.01) annual decrease since the late 1990s; whereas the incidence rate for women has been increasing steadily (P < 0.01) and has not yet reached a similar plateau following a general decline in tobacco consumption in the mid-1980s.5 Lung cancer has a poor prognosis and the five-year relative survival ratio is among the lowest for all types of cancer in Canada (17% in 2013).4

Risk factors

Cigarette smoking is the main risk factor for developing lung cancer, and is associated with over 85% of the cases of this disease in Canada.6 The Canadian Tobacco Use Monitoring Survey reported 44% of adults (4.6 million Canadians) were current or ever smokers (16% are current smokers) in 2012.7 Other factors that increase risk for lung cancer include second hand exposure to cigarette smoke, exposure to radon and other toxic substances (e.g., asbestos, arsenic, diesel exhaust, silica, and chromium), having a first degree relative with lung cancer, and undergoing radiation therapy to the chest.68

Section II. Previous CTFPHC recommendations and recommendations from other guideline developers

Updating its 1994 guidelines on lung cancer screening, in 2003 the CTFPHC determined that there was fair evidence upon which to recommend against using CXR to screen asymptomatic individuals for lung cancer, and insufficient evidence to inform a recommendation for or against using LDCT as a screening test for asymptomatic adults.1 Ten years ago (2004), the United States Preventive Services Task Force (USPSTF) concluded there was insufficient evidence to recommend for or against screening asymptomatic persons for lung cancer using either CXR or LDCT.9 Newly published mortality results from the NLST appear to have convinced guideline groups across North America to rethink their recommendations regarding lung cancer screening.10 The USPSTF’s recently (2013) updated recommendation now endorses annual screening using LDCT

American Cancer Society,12 the American College of Chest Physicians,13 the American Lung Association,14 the American Association for Thoracic Surgery,15 and the National Comprehensive Cancer Network.16 Likewise, in 2013 Cancer Care Ontario issued new guidelines recommending the use of LDCT to screen asymptomatic high risk adults for lung cancer.17

Section III. Scan of new evidence since previous recommendation

Results from the NLST trial were first published in 2011.10 This trial compared screening with LDCT to screening with CXR in a sample of high risk men and showed a 20% relative reduction in lung cancer mortality for LDCT over a median follow-up of 6.5 years.10 Several other lung cancer screening trials are underway and have published preliminary results for LDCT testing, although they have not shown the same mortality benefit as observed by the NLST.18192021222324 Systematic reviews on the benefits of screening for lung cancer using LDCT have been published, including a 2013 Cochrane Review25 and the systematic review that supported the most recent USPSTF recommendation.26

Section IV. Review approach

Figure 1

figure showing analytic framework
Table 1: GRADE table for each screen (low dose computed tomography, chest x-ray, or sputum cytology)
Outcome Type Summary measure of effect
Lung cancer mortality Events/binary Risk ratio (RR)
All-cause mortality Events/binary Risk ratio (RR)
Harms—Overdiagnosis Proportion/percentage Pooled effect size
Harms from follow-up tests
Hospitalization or medical intervention Proportion/rates Pooled effect size
Death Proportion/rates Pooled effect size
Table 2: Inclusion and exclusion criteria (GRADE rating)
Criterion Inclusion Exclusion
Population Adults ≥ 18 years of average risk and high risk who are not suspected of having lung cancer (e.g. may have a cough); includes current, former, and second-hand smokers; as well as those with exposures to substances that may affect risk, as well as other identified factors that may increase risk Adults ≥ 18 years suspected of having lung cancer or previously diagnosed with lung cancer; individuals under the age of 18 years
Intervention Low dose computed tomography, chest x-ray, or sputum cytology
Comparator No screening, studies that compare two or more screening tests Studies with no comparator except for the harms studies which might not have a comparison group
Patient-important outcomes (GRADE ranking)
  • All-cause mortality (9)
  • Lung cancer mortality (9)
  • Smoking cessation rate (6)
  • Stage at diagnosis (6)
  • Incidental findings (such as diagnosis of a thoracic aneurysm; 6)
Harms (GRADE ranking)
  • Overdiagnosis (9)
  • Death from follow-up testing (9)
  • Hospitalization or medical intervention (such as emergency room visits) from follow-up testing (7)
  • False positives and consequences (e.g. overtreatment; 6)
  • Negative consequences of incidental findings (such as diagnosis of COPD; 6)
  • Anxiety (5)
  • Quality of life (5)
  • Infection from follow-up testing (5)
  • Bleeding from follow-up testing (5)
Study design
  • RCTs for screening benefits
  • Any quantitative study for harms
case-controls, case series and ecological

GRADE rating: 7–9 = critical; 4–6 = important; 1–3 = not important (thus, not included in table)

Section V. Planned schedule and timeline

  • Draft Protocol: March 2014
  • Final Protocol: May 2014
  • Draft Evidence Review: September 2014
  • Final Evidence Review: January 2015
  • Draft Recommendation Statement: January 2015
  • Published Recommendation Statement: June 2015

Literature will be updated 6 weeks prior to publication to ensure that the recommendations include all relevant data. In addition authors of key studies will be contacted to determine if they are planning to release data on their trials in the immediate future.


  1. Lung cancer mortality, all-cause mortality, smoking cessation rates, stage at diagnosis

  2. Ongoing trials


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