1. The National Lung Screening Trial:
Overview and Study Design
Nahid Sherbini
Radiology. 2011 January; 258(1): 243-253.Published online 2011January.
10.1148/radiol.10091808

2. Introduction
• The National Lung Screening Trial (NLST) is
a multicenter, randomized controlled trial (RCT)
Comparing:
Low-dose CT with--- CXR
screening of current and former heavy smokers for
lung cancer.
This is the largest randomized study of lung cancer
screening in a high-risk population to date.

3. The Magnitude of the Lung Cancer Problem
• Lung cancer deaths^ 25% of all cancer deaths
• While smoking cessation reduces the
elevated risk of lung cancer, former smokers
remain at elevated risk relative to never
smokers .

4. Lung Cancer Screening
• Clinical stage at diagnosis is a major
determinant of survival after therapy .

7. NLST Description/Design Overview
• Started in Sep 2002 – April 04
• Cohort - 53,456 participants
• Participant was randomized to:
a baseline
2 annual screenings
• By either low-dose CT OR CXR.

8. Endpoints
• The primary endpoint of the NLST is lung
cancer mortality.
• Secondary endpoints include all-cause
mortality, incidence of lung cancer, lung
cancer case survival (as measured from date
of diagnosis), and lung cancer stage
distribution.

11. Sample Size Considerations
• Estimated by using data from the Mayo Lung
Project With 25000 participants enrolled in
each of years 1 and 2 of the trial.
• Statistical power of 90% for detecting a 21%
reduction in lung cancer mortality in the low-
dose CT arm relative to the CXR arm.

13. Low-Dose CT Screening
• Multidetector (ie, at least 4 detectors) whole
chest scanned in a single maximal breath hold
and to achieve good resolution.
• Utilized a low radiation exposure protocol ( 2
mSv, compared with 7 mSv for a standard-dose
diagnostic chest CT examination ) .

14. Interpretations
• Positive findings were defined
as a noncalcified nodule ≥4 mm on CT scan or any
noncalcified nodule on x-ray.

15. Interpretations and Recommendations

16. False Positive
• CT 96.4%
• CXR 94.5%

17. Results

18. Discussion
• The NLST is the only has adequate statistical
power to detect a modest reduction in lung
cancer mortality .
• The largest in Europe “ NELSON trial,
randomized to low-dose CT or community
care”.
• NLST, is providing a definitive assessment of
harms and benefits associated with low-dose
CT screening.

19. Interim Analysis in November 2010
• The trial was stopped after they found a
statistically significant benefit for CT scanning.
• At a median follow-up of 6.5 years

20. Interim Analysis in November 2010
CT GROUP
• 645 cases of lung cancer /
100,000 person
• (1060 cancers)
• 247 lung cancer deaths
• Mortality reduction 20.0 %
(95% CI 3.8-26.7).
• All-cause mortality reduction
6.7 %(CI 1.2-13.6 percent)
CXR GROUP
• 572 cases /
100,000 person
• (941 cancers)
• 309 deaths

21. Complication occurred
• CT 1.4 %
• CXR 1.6%

22. MORE FINDINGS
CT group
• LESS stage IV cancers were
observed.
• Stage I or II (70 % of CT-
detected and), except for small
cell cancers that accounted for
less than 10 % of detected
cancers.
• Chest CT identified a
preponderance of
adenocarcinomas.
CXR group
• 56.7 %detected

23. Results

24. In summary
• CT screening reduced mortality in a high-risk
population, compared to CXR .
• The number needed to screen with low-dose CT to
prevent one lung cancer death was 320 in the NLST.
• Cost of screening per life saved is unknown but likely to
be high.
• The high (≈95%) false-positive rate leading to the need
for additional studies, the need for ongoing screening.
• Low absolute number of deaths prevented (73 per
100,000 person years).