A large randomized trial showed that low-dose CT screening reduced the risk of lung-cancer death by 20% among long-time smokers. Recent guidelines support consideration of screening but with attention to the possibility of false positive results and associated risks. Read the latest Clinical Practice review on this topic.
Despite advances in diagnosis, staging, and treatment, only 18% of patients with lung cancer are still alive 5 years after diagnosis. Clinicians, scientists, and advocates have long sought a safe and effective screening test to identify lung cancer during its preclinical phase, when it is presumed to be more amenable to curative treatment.
•What was the NLST and what were its findings?
The NLST included more than 50,000 persons enrolled at 33 U.S. centers and has thus far provided the strongest evidence regarding the potential benefits of lung-cancer screening. Participants were 55 to 74 years of age, with a smoking history of at least 30 pack-years (former smokers had to have quit within the previous 15 years); they were randomly assigned to three rounds of annual screening with low-dose CT [computed tomography] or chest radiography. The NLST showed a 20% reduction in lung-cancer mortality with low-dose CT versus chest radiography (247 vs. 309 deaths per 100,000 patient-years of follow-up). In absolute terms, this translated to approximately 3 fewer deaths from lung cancer per 1000 high-risk persons who underwent low-dose CT screening.
•How common were false positive findings and complications of invasive testing in the NLST?
False positive findings were common with low-dose CT, but complications of invasive testing were not. Across all three rounds of screening, 39% of the participants in the low-dose CT group had at least one positive result; more than 95% of these findings were falsely positive. Most patients with positive screening-test results required follow-up imaging. After three rounds of screening, a minority of participants underwent invasive tissue sampling by means of needle biopsy (2%), bronchoscopy (4%), or surgery (4%). Relatively few of the surgeries (24%) were performed in patients with benign nodules, but most of the nonsurgical biopsies (73%) revealed benign findings and therefore were potentially avoidable. Among participants with a positive screening-test result in the low-dose CT group, 1% had at least one complication related to invasive testing, but only 20% of these complications occurred among participants who did not have lung cancer.
Morning Report Questions
Q: What uncertainties do the authors highlight about lung-cancer screening with low-dose CT?
A: Several important questions about low-dose CT screening remain unanswered, and screening continues to be controversial. A key controversy is whether the NLST results are applicable to the Medicare population in the United States. A related question is how to optimize the selection of candidates for screening. The potential benefits of screening are greatest in persons who are at the highest risk for death from lung cancer. Although limiting screening to persons at highest risk represents the most efficient approach to screening, extending eligibility criteria to include those at lesser risk will inevitably prevent a greater number of lung-cancer deaths, albeit less efficiently. The potential harms of screening warrant additional consideration. Patients at high risk for procedure-related complications and those with limited life expectancy owing to chronic illness have less to gain from screening than those at low risk and those without chronic illness, respectively. Ultimately, the trade-offs will need to be weighed by patients and their physicians. To facilitate a personalized approach, models have been developed that estimate individualized risks of lung-cancer death and predict complications of needle biopsy and lung-cancer surgery, although further studies are needed to determine which models perform best. There is also uncertainty about whether the relatively low risks of invasive testing for benign condition and procedure-related complications observed in the NLST can be replicated in community-based practice.
Q: Is there evidence that lung-cancer screening programs will reduce rates of smoking?
A: Sparse data from randomized, controlled trials of low-dose CT screening have been inconsistent and are inconclusive thus far as an answer to the question of whether participation in a screening program improves rates of smoking cessation. A possible unintended consequence of screening is that some current smokers with negative results on low-dose CT will be falsely reassured that they do not have lung cancer and will therefore continue to smoke. Several studies have shown that rates of smoking cessation are higher among persons with positive screening-test results than among those with negative results.