Download Lung Cancer Screening: An Evidence

Lung Cancer Screening:
An Evidence-Based Overview
Sean A. Kennedy MD
Ravi Shergill BSc
Mark O. Baerlocher MD, FRCPC
McMaster University, Hamilton, ON
Royal Victoria Hospital, Barrie, ON
All three authors have no conflicts of interest to
declare.
Learning Objectives
Review the epidemiology of lung cancer.
2.  Review the principles of screening programs.
3.  Review the latest evidence for and against
lung cancer CT screening, including the
National Lung Screening Trial and other
ongoing trials.
4.  Review associated risks, limitations and
implementation challenges of lung cancer
screening.
1. 
Epidemiology
  Lung
cancer is most significant cause of
cancer-related death globally.
  27% of all cancer-related death in US.
Epidemiology
  After
an initial decline in incidence with public
health successes in the 1980s and 90s, lung
cancer is now on the rise.
  Mortality no longer declining in males.
  Mortality increasing in females.
Epidemiology
  Survival
strongly dependent on early treatment.
Current Mean 5 Year Survival
from Diagnosis= 15%
Mean
“Principles and Practice of Screening for
Disease” (WHO, 1968)
In order for a screening program to be acceptable it must
address a:
  Significant public health issue
  Treatable disease with defined practices on who to treat
  Disease with a latent stage where treatment can change
outcomes and the progression is understood
  Disease that can be tested for
Additionally, testing must be:
  Acceptable (ie non/minimally invasive)
  Economically sensible
  Continuous, ongoing process
Past Screening Programs
  Chest
X-ray (1-3x per year)
  Sputum
cytology
  Combined
cytology
chest X-ray and sputum
Past Screening Programs
 
Systematic review of 9 trials (8 RCTs) with 453 965
subjects looked at whether sputum cytology, CXR or CT
screening affects lung cancer mortality.
 
No significant mortality reduction when screening with
chest x-ray and sputum cytology was compared with
chest x-ray alone (RR 0.88, 95% CI:0.74-1.03).
 
PLCO trial annual CXR vs no CXR for 4 years (>150 000
participants, age 55-74, general population). No
significant mortality reduction. (RR 1.05, 95% CI,
0.98-1.12).
 
Conclusion: CXR and/or sputum cytology
NOT recommended for screening.
Manser et al Screening for lung cancer. Cochrane Review June 21 2013.
National Lung Screening Trial
 
NLST enrolled a high risk population of 53 454
current and former smokers.
 
Inclusion criteria:
  Age 55 to 74
  >30 pack year history of smoking
  Current smoker or quit within past 15 years
 
Participants were randomized to annual screening
with either low-dose helical CT or single-view chest
radiograph for three years.
National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed
tomographic screening. N Engl J Med. 2011;365(5):395
NLST Definition of Positive Findings
  For
low-dose CT:
  All non-calcified nodules with diameters >4 mm.
  For
CXR:
  All non-calcified nodules and masses.
  Radiologist
overall opinion (ie hilar
adenopathy, pleural disease).
National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed
tomographic screening. N Engl J Med. 2011;365(5):395
C
(A) CT image showing ground-glass RUL nodule.
(B) 20 month followup progression to increasingly solid tumor.
(C) Adenocarcinoma on biopsy.
Source: MassGen Radiology Rounds Vol 4 Issue 8, Aug 2006
NLST Results
  The
study was stopped early at a mean
follow-up time of 6.5 years.
  Lung cancer mortality:
  CT arm 247 per 100 000 person-years
  CXR arm 309 per 100 000 person years
  Relative
mortality benefit of 20.0% (95%
CI, 6.8 to 26.7; P=0.004).
National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic
screening. N Engl J Med. 2011;365(5):395
Ongoing Trials
NELSON Trial
  Dutch
Belgian randomised lung cancer
screening trial (NELSON).
  Only ongoing trial with sufficient power to
detect mortality differences (n=15 822).
  RCT with population similar to NLST.
  Control arm receives usual care (ie no CXR).
  Intervention arm receives CT screen every 1,2
or 2.5 years.
NELSON Trial Registration http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=636
Other Ongoing Trials
Trial Name
Number of
Patients
Comparison
DANTE Trial
2472
Annual CT vs Ongoing (interim three
Usual Care
year results showed
no mortality difference)
Danish Lung Cancer
Screening Trial
(DLCST)
4104
Annual CT vs Ongoing
Usual Care
Multi-centric Italian Lung 4099
Detection Trial (MILD)
Status
Annual CT vs Increased mortality in
Usual Care
screening arm (low
quality study due to
inadequate
randomization and
differences in baseline
characteristics)
Humphrey et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive
services task force recommendation. Ann Intern Med. 2013 Sep 17;159(6):411-20.
Other Ongoing Trials
  A large
pooled analysis of UKLS,
NELSON, MILD, DLCST, ITALUNG,
LUSI and DANTE is planned for
2015/16.
NELSON Trial Registration http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=636
Risks and Concerns
Reproducibility
  Academic
vs community
  The
NLST involved primarily academic
centres with fellowship trained thoracic
radiologists reading the screening CTs.
  Unknown
if applicable on large scale in
community hospitals with general
radiologists.
Gill et al. Controversies in Lung Cancer Screening. J Am Coll Radiol 2013;10:931-936.
False Positives
 
False positives (20% after first screening CT, 30%
after second).
 
7% of these false positives lead to need for
percutaneous, thoracoscopic, open biopsies.
 
Significant anxiety associated with false positives in
other screening programs (not yet demonstrated for
lung cancer screening).
Croswell JM et al. Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial. Ann Intern
Med. 2010 Apr 20;152(8):505-12.
Broderson et al. Long Term Psychosocial Consequences of False-Positive Screening Mammography. Ann Fam Med
Mar/Apr 2013 Vol 11 no 2; 106-115.
Radiation Dose
  Continued
advances in dose reduction
allow for minimal radiation exposure
(~1.5 mSv per screening CT).
  Potentially >20 years of annual chest CT
  Unclear potential risk for radiationinduced cancer.
Baerlocher et al. Discussing radiation risks associated with CT scans with patients. JAMA. 2010 Nov 17;304(19):2170-1.
American College of Radiology and Radiological Society of North America (April 2012). Patient Safety: Radiation Dose in X-Ray and
CT Exams . Retrieved March 23, 2015.
Cost Efficacy
No studies yet evaluate cost effectiveness
in Canada’s public health care system.
  Studies in US forecast screening will be
cost effective at <$19 000 (USD) per lifeyear saved.
  By comparison:
 
  Biennial breast screening costs $18 999 (USD)
per life-year saved
  Colon cancer screening costs $11 900 (USD)
per life-year saved
Gill et al. Controversies in Lung Cancer Screening. J Am Coll Radiol 2013;10:931-936.
Pyenson et al. Offering lung cancer screening to high-risk medicare beneficiaries saves lives and is cost-effective: an actuarial
analysis. Am Health Drug Benefits. 2014 Aug;7(5):272-82.
Propagation of Smoking?
  Some
concerns whether effective
screening and negative test results
could paradoxically reassure smokers,
reducing smoking cessation rate.
  However,
an analysis of current smokers
in NELSON found screening had no
impact on quit rate.
Van Der Aalst et al. The impact of a lung cancer computer tomography screening result on smoking abstinence. Eur
Respir J. 2011 Jun;37(6):1466-73.
Organizations Endorsing CT Lung
Screening
  American
Cancer Society
  American College of Chest Physicians
  American Society of Clinical Oncology
  National Cancer Institute
  US Preventive Services Task Force
  CancerCare Ontario
Roberts H et al. Screening High-Risk Populations for Lung Cancer: Guideline Recommendations. Journal of
Thoracic Oncology: October 2013;8(10):1232-1237.
Conclusion
  Lung
cancer screening holds great
promise in improving lung cancer
mortality.
  Numerous ongoing trials should help to
clarify the role of screening for lung
cancer.
  It remains to be seen if and how such a
program will be implemented in the
Canadian setting on a provincial or
national level.