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

U Pastorino, M Silva, S Sestini, F Sabia, M Boeri, A Cantarutti, N Sverzellati, G Sozzi, G Corrao, A Marchianò, U Pastorino, M Silva, S Sestini, F Sabia, M Boeri, A Cantarutti, N Sverzellati, G Sozzi, G Corrao, A Marchianò

Abstract

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 5 years, and its impact on overall and LC specific mortality at 10 years.

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, 39 293 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 5 years by exclusion of LCs and deaths that occurred in the first 5 years.

Results: The LDCT arm showed a 39% reduced risk of LC mortality at 10 years [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.

Keywords: early detection; low-dose computed tomography; lung cancer; mortality; overdiagnosis; screening.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.
Figure 1.
Cumulative overall mortality and lung cancer mortality, by arm over 10 years of follow-up.
Figure 2.
Figure 2.
Landmark analysis of cumulative overall mortality and lung cancer mortality, by arm beyond 5 years.

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