Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy

Background The National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5years, and its impact on overall and LC specific mortality at 10years. Design The Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n=2376), with further randomization to annual (n=1190) or biennial (n=1186) LDCT for a median period of 6 years, or control arm (n=1723) without intervention. Between 2005 and 2018, 39293 person-years of follow-up were accumulated. The primary outcomes were 10-year overall and LC specific mortality. Landmark analysis was used to test the long-term effect of LC screening, beyond 5years by exclusion of LCs and deaths that occurred in the first 5years. Results The LDCT arm showed a 39% reduced risk of LC mortality at 10years [hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.39-0.95], compared with control arm, and a 20% reduction of overall mortality (HR 0.80; 95% CI 0.62-1.03). LDCT benefit improved beyond the 5th year of screening, with a 58% reduced risk of LC mortality (HR 0.42; 95% CI 0.22-0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49-0.94). Conclusions The MILD trial provides additional evidence that prolonged screening beyond 5 years can enhance the benefit of early detection and achieve a greater overall and LC mortality reduction compared with NLST trial. ClinicalTrials.gov identifier NCT02837809.