Results from an Italian lung cancer screening trial showed that long-term annual or biennial computed tomography (CT) screening may reduce lung cancer-specific mortality beyond 10 years. The Multicentric Italian Lung Detection (MILD) study is actually the first trial to look at continued screening beyond 5 years, and the researchers found that mortality due to lung cancer was reduced by 39% [hazard ratio (HR) 0.61; 95% CI, 0.39-0.95].1 They also showed that active surveillance of subsolid lesions could reduce overdiagnosis and unnecessary surgery.

The study’s small size, as well as some irregularities with randomization, suggest the results should be interpreted cautiously. Still, pulmonologists hope the findings will boost support for lung screening programs and stimulate additional research.

Lung cancer is the leading cause of cancer death worldwide, but screening rates remain low.

Related Articles

The 2 largest lung cancer screening trials to date have been the US National Cancer Institute’s National Lung Screening Trial (NLST), which enrolled more than 50,000 patients, and the Netherlands-based NELSON trial, which included more than 15,000 participants. The NLST compared lung screening using low-dose CT with chest X-ray. The investigators conducted 3 annual screenings and detected a 20% reduction in mortality during a follow-up of 6 to 7 years.2 The NELSON trial conducted screenings at 1 year, 3 years, and 5.5 years; compared with no screening, they found a 26% reduction in lung cancer deaths after 10 years of follow up.3

The MILD trial, helmed by Ugo Pastorino, MD, of the Istituto Nazionale dei Tumori in Milan, Italy, intended to go beyond NLST and NELSON. “The original design was to try to do something different from what was the conventional concept,” Dr Pastorino said.

They initially planned to enroll 10,000 participants, who would be randomized to a control arm or a intervention arm. Those selected for intervention would then be assigned to either an annual or biennial screening schedule.

“Then, of course, we faced huge problems with funding and randomization,” Dr Pastorino said. “We had to accept a smaller size [sample].”

At the outset, the Institutional Ethics Committee prohibited the group from assigning participants to a control arm. The first 653 enrollees all received screening, either annually or every 2 years. After that, the team got the green light to begin randomizing the participants into a control arm. Eventually they enrolled 3446 more individuals—but this was still fewer enrollees than their original goal of 10,000 participants.

Of these enrollees, half received no screening, and the other half of the cohort was divided evenly into the annual or biennial screening protocol groups. However, if a scan revealed a suspicious lesion, a patient on the biennial schedule would be shifted to annual screenings.

After 5 years, the study showed no protective benefit of screening on mortality.4 Now, analysis of 10-year results suggests screening produced a sizable reduction in the number of deaths from lung cancer—but again, some study design issues preclude the formation of a concrete conclusion from the data.