LUNG CANCER SCREENING

Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer Death

Kovalchik SA, Tammemagi M, Berg CD, et al

N Engl J Med. 2013;369:245-254

Background

The value of lung cancer screening was demonstrated by the National Lung Screening Trial (NLST),which revealed a 20% improvement in overall survival conferred by annual low-dose chest CT screening, compared with chest x-rays over 3 years in a population of patients aged 55-74 with a 30 pack-year smoking history and who quit smoking less than 15 years earlier.^[1] Since then, however, lung cancer screening has yet to be widely adopted, with many high-risk patients who were eligible under the NLST criteria failing to be screened. Meanwhile, lung cancer screening is applied to other patient populations, such as younger patients or anxious never-smokers with a family history of lung cancer, who may not have qualified for this study.

The challenges stem largely from skepticism about cost of screening and concern over detrimental effects of false-positive results of small lung nodules that ultimately are benign but which lead to significant anxiety, additional follow-up imaging studies, and sometimes invasive procedures. Can we save lives with early detection without causing an epidemic of anxiety over benign lung nodules at a prohibitive cost?

Study Summary

A very recent report by Kovalchik and colleagues evaluated the data from NLST, stratifying patients within the eligible population by level of risk. This report provides a clear illustration of the importance of degree of risk in determining the value of screening. Using a complex multivariate analysis to define risk more precisely, the investigators identified relevant variables for risk for lung cancer, including age, sex, years since quitting, pack-years of tobacco exposure, and family history, and divided the participants in the screening study into 5 quintiles. As we might expect, the results demonstrated striking differences in the efficacy and significance of an abnormal result depending on whether people within the spectrum of NLST eligibility were on the higher or lower end of that continuum.

Specifically, within the highest risk quintile, CT screening required screening of 161 people and detected 65 false positives for each life saved from lung cancer, quite favorable within the realm of screening for cancer. In contrast, the results were remarkably less favorable for patients who were eligible but were within the lowest risk quartile: here, chest CT screening needed to be performed on over 5000 people and detected 1648 false positives for each lung cancer death prevented. With an improvement in overall survival of 20% in the entire population, this means that the higher-risk patients actually experienced a far greater benefit than that, while those who were lower-risk received much less benefit.