Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening
- Study type
- Clinical trial
- Study name
- NLST
- Design
- Randomised multicentre trial in 33 US medical centres comparing low-dose CT with plain chest radiography
- Sample size
- 53,454 people
- Source
- N Engl J Med · 2011
- Trial registration
- NCT00047385
In plain words
In this large study, more than 53 thousand heavy current or former smokers had either a low-dose CT scan of the lungs or a plain chest X-ray once a year (for three years in a row). In the CT group, deaths from lung cancer were 20% lower, because cancers were found earlier, at a stage that could be treated. On the other hand, many people had a "suspicious finding" that in the end was not cancer, so the decision to be screened should be made with your doctor, knowing the benefits and the downsides.
Key results
Treatment arms and regimens
Three annual screening rounds (T0, T1, T2) with low-dose helical CT without contrast, from the neck to the diaphragm in a single breath-hold (26,722 people). Definition of a positive test: any non-calcified nodule ≥4 mm in diameter (or other findings such as adenopathy or effusion). The diagnostic follow-up approach was not mandated.
Three annual screening rounds with single-view posteroanterior chest radiography in the standing position (26,732 people). Definition of a positive test: any non-calcified nodule or mass.
Source of the regimen details: Abstract and full text of the paper (PMC4356534) and ClinicalTrials.gov NCT00047385 (screening method; no drug)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
People aged 55 to 74 with a smoking history of at least 30 pack-years; current smokers or those who had quit within the past 15 years. Exclusion criteria: previous lung cancer diagnosis, chest CT within the past 18 months, haemoptysis, or unexplained weight loss of more than 6.8 kg in the past year. Enrolment from August 2002 to April 2004 at 33 US centres; median follow-up 6.5 years.
Endpoints
Primary endpoint: death from lung cancer. Secondary endpoints: death from any cause, lung cancer incidence and the rate of positive screening results.
Safety and side effects
The main "harm" of screening was false-positive results: 96.4% of positive findings in the CT group were ultimately not cancer and may lead to further imaging or diagnostic procedures. Complications of the screening tests themselves were few and minor. At least one complication after a diagnostic procedure for a positive test occurred in 1.4% of the CT group and 1.6% of the radiography group; a major complication after an invasive procedure was seen in 0.06% of positive CT tests without cancer and 11.2% of tests leading to a cancer diagnosis. 16 people in the CT group (10 with lung cancer) and 10 in the radiography group (all with cancer) died within 60 days of an invasive diagnostic procedure.
Clinical significance and place in guidelines
NLST was the first large trial to show that lung cancer screening with low-dose CT reduces deaths from this cancer, and it became the basis of screening recommendations in the United States. In 2021 the US Preventive Services Task Force (USPSTF) recommended annual screening for people aged 50 to 80 with at least 20 pack-years of smoking history (current smokers or those who quit within the past 15 years); broader criteria than the NLST entry criteria.
Limitations
The control group had chest radiography, not no screening; only three screening rounds were done; participants were mostly white and more highly educated than the general population, and screening was done in experienced centres. The high false-positive rate and the possibility of overdiagnosis should be considered in decision-making.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.