Results from the National Lung Screening Trial of more than 50,000 people at high risk for lung cancer showed that patients who undergo screening with helical low-dose CT scanning are less likely to die from lung cancer.
NLST compared low-dose CT screening against screening with chest radiography. From August 2002 through September 2007, researchers assigned 26,722 people to CT screening and another 26,732 to radiography. Participants underwent three screenings at 1-year intervals (T0, T1 and T2).
Eligible participants were between 55 and 74 years of age at the time of randomization, had a history of cigarette smoking of at least 30 pack-years and, if they were former smokers, had quit within the previous 15 years. Anyone who had been previously diagnosed with lung cancer, undergone chest CT within 18 months before enrollment, had hemoptysis, or had an unexplained weight loss of more than 15 lb in the preceding year were excluded.
The disease-specific death rate was 247 per 100,000 person-years in the CT group vs. 309 deaths per 100,000 person-years in the radiography group. Researchers observed a 20% relative reduction in the rate of disease-specific death associated with CT screening (95% CI, 6.8-26.7). The number needed to screen with low-dose CT to prevent one death from lung cancer was 320.
There were 1,877 deaths in the low-dose CT group and 2,000 deaths in the radiography group. CT screening was associated with a 6.7% (95% CI, 1.2 to 13.6) reduced rate of all-cause mortality.
Lung cancer accounted for 24.1% of overall deaths and 60.3% of the excess deaths in the radiography group. When deaths from lung cancer were excluded, the reduction in overall mortality associated with CT screening dropped to 3.2% and was not significant (P=0.28).
The American Lung Association released a statement saying that the group is “optimistic” that findings from NLST will eventually translate to a significant drop in lung cancer mortality. Even while praising the findings, Albert Rizzo, MD, chair-elect of the ALA board of directors and chief of pulmonary and critical care medicine at Christiana Care Health System in Wilmington, Del., reiterated the group’s position that quitting smoking remains the best way to reduce lung cancer risk and deaths.
“Although the National Lung Screening Trial results are an important step forward in the fight against lung cancer, the single most important thing any smoker can do to reduce their chances of developing or dying from lung cancer is to quit smoking,” he said. “The Surgeon General’s 30th Report released in December confirmed that there is no safe level of exposure to tobacco smoke, and the sooner someone quits smoking, the less likely he or she is to develop tobacco-related diseases.”
There was a substantially higher rate of positive screening tests in the low-dose CT group than in the radiography group every year. Sixteen percent of patients in the radiography group had at least one positive screening result compared with 39.1% in the CT group. Low-dose CT identified more than three times the rate of clinically significant abnormalities other than an abnormality suspicious for lung cancer (7.5% vs. 2.1%).
Across the three rounds of screening, 96.4% of the positive results in the low-dose CT group and 94.5% of those in the radiography group were false positive results. Of the total number of low-dose CT screening tests in the three rounds, 24.2% were classified as positive and 23.3% had false positive results. Of the total number of radiographic screening tests in the three rounds, 6.9% were classified as positive and 6.5% had false positive results.
Writing in an accompanying editorial, Harold C. Sox, MD, professor of medicine at The Dartmouth Institute at Dartmouth Medical School, said that more data on cost-effectiveness and the amount of over-diagnosis in NLST is required before instituting a general screening program with low-dose CT.
"According to the authors, '7 million U.S. adults meet the entry criteria for the NLST and an estimated 94 million U.S. adults are current or former smokers.' With either target population, a national screening program of annual low-dose CT would be very expensive, which is why I agree with the authors that policy makers should wait for more information before endorsing lung-cancer screening programs,” he wrote. “The findings of the NLST regarding lung-cancer mortality signal the beginning of the end of one era of research on lung-cancer screening and the start of another. The focus will shift to informing the difficult patient-centered and policy decisions that are yet to come.”