Self-Selection Effects in Smokers Attending Lung Cancer Screening: A 9.5-Year Population-Based Cohort Study in Varese, Italy

Background: We hypothesize that mortality risk profile of participants and nonparticipants in nonrandomized lung cancer (LC) screening of smokers may be different. Methods: In 1997, a population-based cohort of 5815 smokers of Varese Province was invited to nonrandomized LC screening by annual chest x-ray examination for 4 years. LC risk factors and screening participation rate were recorded. Except for screening, the whole cohort received usual care. After 9.5-year observation, we compared mortality of participants versus nonparticipants by assessing age-standardized all-cause mortality rate ratio (MRR) and disease group-specific MRR with 95% confidence intervals (95% CI). Results: Self-selected screening participants were 21% of cohort. Participants were younger (p < 0.001), were more frequently current smokers (p = 0.019), had more pack-years of smoking (p < 0.0001), and had higher rate of LC family history (p < 0.0001) and of occupational LC risk (p < 0.0001) relative to nonparticipants. In logistic regression analysis familial LC, occupational risk and pack-years smoked were significant predictors of participation in screening and of developing LC. Participants displayed a healthy effect, as shown by all-cause MRR = 0.67 (95% CI, 0.53–0.84), all cancers except LC MRR = 0.61 (95% CI, 0.41–0.91), cardiovascular diseases MRR = 0.38 (95% CI, 0.22–0.63), and noncancer disease other than cardiovascular or respiratory MRR = 0.57 (95% CI, 0.34–0.92). The LC mortality (MRR = 1.40; 95% CI, 1.03–1.91) was higher in participants relative to nonparticipants (p = 0.031). Conclusion: The selection effect in LC screening participants was dual: healthy effect and higher LC mortality. In assessing the overall effectiveness of LC screening on a population level, a higher LC mortality risk in participants should be considered.