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National Lung Screening Trial (NLST) Screening

National Lung Screening Trial A Randomized Trial Comparing Low-dose Helical CT With Chest Xray for Lung Cancer

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00047385
Acronym
NLST
Enrollment
53454
Registered
2003-01-27
Start date
2002-08-31
Completion date
2010-10-31
Last updated
2014-05-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer

Keywords

small cell lung cancer, non-small cell lung cancer

Brief summary

RATIONALE: Effective screening tests should help doctors detect lung cancer early and plan curative treatment. It is not yet known whether low-dose helical computed tomography (LDCT) screening is more effective than chest radiography (CXR) screening in reducing death from lung cancer. PURPOSE: Randomized clinical trial to compare the effectiveness of LDCT scan with that of CXR in screening individuals who are at high risk for developing lung cancer.

Detailed description

OBJECTIVES: * Compare whether screening with low-dose helical CT scan vs chest x-ray reduces lung cancer-specific mortality in participants who are at high risk for developing lung cancer. OUTLINE: NLST participants were randomized to either low-dose helical CT or chest x-ray in equal proportions. A total of 53,454 participants were enrolled (26,722 in low-dose CT and 26,732 in chest radiography) at 33 screening centers across the United States. Screening was offered three times (at baseline and two annual follow-up examinations). The primary endpoint of the study was lung cancer mortality. The study arms were compared with regard to overall mortality, lung cancer incidence, and screening-related complications. All low-dose scanners and chest x-ray machines were certified for use and met NLST protocol requirements and American College of Radiology guidelines. Low-dose CT acquisitions and chest radiographs were interpreted by trained radiologists. Participants and their health care provider were informed of study examination results. Participants with abnormalities suspicious for lung cancer were contacted for information regarding diagnostic evaluation. Medical records were collected on diagnostic evaluation, medical complications, and initial treatment. Participants were then contacted at least annually by mail or telephone. The National Lung Screening Trial (NLST) represents the union of two NCI-sponsored efforts, the NCI Lung Screening Study and the American College of Radiology Imaging Network (ACRIN).

Interventions

DEVICElow-dose helical computed tomography

A LDCT is a computerized tomography image with low-dose technique without contrast. The scan is done from the neck to the diaphragm in one breath-hold.

DEVICEchest radiography

The chest x-ray in this study was a single posterior-anterior film done with the participant upright.

Sponsors

American College of Radiology Imaging Network
CollaboratorNETWORK
National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
55 Years to 74 Years
Healthy volunteers
Yes

Inclusion criteria

* Age 55-74 years (pack-years = packs per day \* years smoked) * 30 or more pack-years of cigarette smoking history * Former smokers: quit smoking within the previous 15 years * Ability to lie on the back with arms raised over the head * Signed informed consent form

Exclusion criteria

* Metallic implants or devices in the chest or back, such as pacemakers or Harrington fixation rods * Treatment for, or evidence of, any cancer other than nonmelanoma skin cancer or carcinoma in situ (with the exception of transitional cell carcinoma in situ or bladder carcinoma in situ) in the 5 years prior to eligibility assessment * History of lung cancer * History of removal of any portion of the lung, excluding needle biopsy * Requirement for home oxygen supplementation * Participation in another cancer screening trial * Participation in a cancer prevention study, other than a smoking cessation study * Unexplained weight loss of more than 15 pounds in the 12 months prior to eligibility assessment * Recent hemoptysis * Pneumonia or acute respiratory infection treated with antibiotics in the 12 weeks prior to eligibility assessment * Chest CT examination in the 18 months prior to eligibility assessment

Design outcomes

Primary

MeasureTime frameDescription
Lung Cancer DeathsAll events through December 31, 2009; median follow-up 6.5 years.Lung cancer deaths confirmed in participants by Endpoint Verification if available, otherwise by death certificate.

Secondary

MeasureTime frameDescription
Lung Cancer DiagnosesAll events through December 31, 2009; median follow-up 6.5 yearsLung cancer diagnoses confirmed by medical record abstraction.
Complications of Diagnostic Evaluation Following a Positive Screening Test.One year from screening examinationNumber of participants who experienced complications during diagnostic work-up of a screening CT or CXR that was suspicious for lung cancer.
Deaths From All Causes in All Randomized Participants.All events through December 31, 2009; median follow-up 6.5 years.Deaths from all causes were compared between the low-dose CT group and the chest radiography group among all randomized participants.
T1 Screening ResultsT1 (one year after entry)Results of radiologist's interpretation of images from LDCT or CXR screening exam at T1. Includes a comparison with images from T0 screen.
T2 Screening ResultsT2 (two years after entry)Results of radiologist's interpretation of images from LDCT or CXR screening exam at T2. Includes a comparison with images from T0 and T1 screens.
T0 (Baseline) Screening ResultsT0 (at study entry)Results of radiologist's interpretation of images from LDCT or CXR screening exam at T0.

Countries

United States

Participant flow

Recruitment details

Recruitment was from August 2002 through April 2004 at 33 NLST sites.

Pre-assignment details

Participants signed a study informed consent prior to being randomized to a study arm.

Participants by arm

ArmCount
Low-Dose CT
Participants undergo low-dose helical CT examination.
26,722
Chest X-ray
Participants undergo chest x-ray examination.
26,732
Total53,454

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyDeath before any screening25
Overall StudyEligible for screening but had no screen260492
Overall StudyLung Cancer diagnosed before screening53

Baseline characteristics

CharacteristicChest X-rayLow-Dose CTTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
7110 Participants7110 Participants14220 Participants
Age, Categorical
Between 18 and 65 years
19622 Participants19612 Participants39234 Participants
Age, Continuous61.4 years
STANDARD_DEVIATION 5
61.4 years
STANDARD_DEVIATION 5
61.4 years
STANDARD_DEVIATION 5
Region of Enrollment
United States
26,732 participants26,722 participants53454 participants
Sex: Female, Male
Female
10970 Participants10952 Participants21922 Participants
Sex: Female, Male
Male
15762 Participants15770 Participants31532 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 26,7220 / 26,732
serious
Total, serious adverse events
0 / 26,7222 / 26,732

Outcome results

Primary

Lung Cancer Deaths

Lung cancer deaths confirmed in participants by Endpoint Verification if available, otherwise by death certificate.

Time frame: All events through December 31, 2009; median follow-up 6.5 years.

Population: All participants randomized were analyzed. An intention-to-treat analysis was performed.

ArmMeasureValue (NUMBER)
LDCT ScreeningLung Cancer Deaths356 Participants
CXR ScreeningLung Cancer Deaths443 Participants
Comparison: Alternative hypothesis: LDCT screening reduces lung cancer mortality relative to chest x-ray.~Power: 90% for a 20% reduction in lung cancer mortality.p-value: 0.00495% CI: [0.733, 0.932]Weighted log-rank (details below)
Secondary

Complications of Diagnostic Evaluation Following a Positive Screening Test.

Number of participants who experienced complications during diagnostic work-up of a screening CT or CXR that was suspicious for lung cancer.

Time frame: One year from screening examination

Population: The units analyzed were positive screening exams with documented diagnostic follow-up. If participant received 3 positive screens with documented follow-up after each one, he/she would be counted 3 times in the number of units analyzed.

ArmMeasureValue (NUMBER)
LDCT ScreeningComplications of Diagnostic Evaluation Following a Positive Screening Test.245 Pos. screens w/ complications
CXR ScreeningComplications of Diagnostic Evaluation Following a Positive Screening Test.81 Pos. screens w/ complications
Secondary

Deaths From All Causes in All Randomized Participants.

Deaths from all causes were compared between the low-dose CT group and the chest radiography group among all randomized participants.

Time frame: All events through December 31, 2009; median follow-up 6.5 years.

Population: All participants randomized were analyzed. An intention-to-treat analysis was performed.

ArmMeasureValue (NUMBER)
LDCT ScreeningDeaths From All Causes in All Randomized Participants.1877 Participants
CXR ScreeningDeaths From All Causes in All Randomized Participants.2000 Participants
Comparison: Alternative hypothesis: LDCT screening reduced all-cause mortality relative to chest x-ray.p-value: 0.0295% CI: [0.864, 0.988]Weighted log-rank (details below)
Secondary

Lung Cancer Diagnoses

Lung cancer diagnoses confirmed by medical record abstraction.

Time frame: All events through December 31, 2009; median follow-up 6.5 years

Population: All participants randomized were analyzed. An intention-to-treat analysis was performed.

ArmMeasureValue (NUMBER)
LDCT ScreeningLung Cancer Diagnoses1060 Participants
CXR ScreeningLung Cancer Diagnoses941 Participants
95% CI: [1.03, 1.23]
Secondary

T0 (Baseline) Screening Results

Results of radiologist's interpretation of images from LDCT or CXR screening exam at T0.

Time frame: T0 (at study entry)

Population: All participants randomized were analyzed.

ArmMeasureGroupValue (NUMBER)
LDCT ScreeningT0 (Baseline) Screening ResultsSignificant abnor. not suspicious for lung cancer2695 Participants
LDCT ScreeningT0 (Baseline) Screening ResultsEligible but not screened406 Participants
LDCT ScreeningT0 (Baseline) Screening ResultsNo, or minor abnormality16423 Participants
LDCT ScreeningT0 (Baseline) Screening ResultsNot eligible for screen7 Participants
LDCT ScreeningT0 (Baseline) Screening ResultsPositive7191 Participants
CXR ScreeningT0 (Baseline) Screening ResultsNot eligible for screen8 Participants
CXR ScreeningT0 (Baseline) Screening ResultsPositive2387 Participants
CXR ScreeningT0 (Baseline) Screening ResultsSignificant abnor. not suspicious for lung cancer785 Participants
CXR ScreeningT0 (Baseline) Screening ResultsNo, or minor abnormality22863 Participants
CXR ScreeningT0 (Baseline) Screening ResultsEligible but not screened689 Participants
Secondary

T1 Screening Results

Results of radiologist's interpretation of images from LDCT or CXR screening exam at T1. Includes a comparison with images from T0 screen.

Time frame: T1 (one year after entry)

Population: All participants randomized were analyzed

ArmMeasureGroupValue (NUMBER)
LDCT ScreeningT1 Screening ResultsNot eligible for screen437 Participants
LDCT ScreeningT1 Screening ResultsPositive6901 Participants
LDCT ScreeningT1 Screening ResultsSignificant abnor. not suspicious for lung cancer1519 Participants
LDCT ScreeningT1 Screening ResultsNo, or minor abnormality16295 Participants
LDCT ScreeningT1 Screening ResultsEligible but not screened1570 Participants
CXR ScreeningT1 Screening ResultsEligible but not screened2321 Participants
CXR ScreeningT1 Screening ResultsNo, or minor abnormality22178 Participants
CXR ScreeningT1 Screening ResultsPositive1482 Participants
CXR ScreeningT1 Screening ResultsNot eligible for screen322 Participants
CXR ScreeningT1 Screening ResultsSignificant abnor. not suspicious for lung cancer429 Participants
Secondary

T2 Screening Results

Results of radiologist's interpretation of images from LDCT or CXR screening exam at T2. Includes a comparison with images from T0 and T1 screens.

Time frame: T2 (two years after entry)

Population: All participants randomized were analyzed

ArmMeasureGroupValue (NUMBER)
LDCT ScreeningT2 Screening ResultsSignificant abnor. not suspicious for lung cancer1408 Participants
LDCT ScreeningT2 Screening ResultsEligible but not screened1840 Participants
LDCT ScreeningT2 Screening ResultsNo, or minor abnormality18640 Participants
LDCT ScreeningT2 Screening ResultsNot eligible for screen780 Participants
LDCT ScreeningT2 Screening ResultsPositive4054 Participants
CXR ScreeningT2 Screening ResultsNot eligible for screen622 Participants
CXR ScreeningT2 Screening ResultsPositive1174 Participants
CXR ScreeningT2 Screening ResultsSignificant abnor. not suspicious for lung cancer361 Participants
CXR ScreeningT2 Screening ResultsNo, or minor abnormality21811 Participants
CXR ScreeningT2 Screening ResultsEligible but not screened2764 Participants

Source: ClinicalTrials.gov · Data processed: Apr 7, 2026