MILD: Prolonged lung cancer screening reduces long-term mortality
BY SUSAN LONDON
Extending the duration of low-dose CT screening for lung cancer among current or former heavy smokers beyond 5 years further reduces risks of lung cancer and all-cause mortality, the randomized controlled Multicentric Italian Lung Detection (MILD) trial has found.
The previous National Lung Screening Trial showed that lung cancer screening with annual low-dose CT for 3 years reduced lung cancer mortality relative to chest radiography (N Engl J Med. 2011;365:395-409), but European trials have failed to find a significant benefit of low-dose CT screening relative to observation at 5 years.
The MILD investigators, led by Ugo Pastorino, MD, director of thoracic surgery at the Fondazione IRCCS at the National Cancer Institute in Milan, randomized more than 4,000 current or former heavy smokers either to low-dose CT screening every year or every other year or to observation as a control. PET imaging and active surveillance of lower-risk
Main results, reported in the Annals of Oncology, showed that, compared with control peers, screened individuals had a significant 39% reduction in the 10-year risk of lung cancer mortality – the trial’s primary endpoint – and a nonsignificant 20% reduction in the 10-year risk of all-cause mortality. Importantly, in analyses restricted to individuals still alive and free of lung cancer at 5 years, screening had a larger survival benefit with significant 58% and 32% reductions in risks of these outcomes, respectively.
“MILD is the only randomized lung cancer screening trial designed to assess the value of prolonged intervention,” Dr. Pastorino and coinvestigators note. “The MILD trial provides additional evidence that prolonged intervention beyond five years can enhance the benefit of screening. The incremental effect of prolonged [lung cancer] screening achieved a significant mortality reduction at 10 years, notwithstanding biennial rounds and active surveillance.”
“MILD is the only randomized lung cancer screening trial designed to assess the value of prolonged intervention,”
The 4,099 participants in MILD were current or former smokers (minimum 20 pack-year smoking history) aged 49-75 years. They were randomized to a low-dose CT screening arm, with further randomization to an annual or biennial schedule, or to a control arm that did not receive any intervention. The median duration of screening was 6.2 years.
Initial trial results, previously reported (Eur J Cancer Prev. 2012;21:308-15), showed no significant reduction in 5-year mortality in the combined screening arm relative to the control arm.
However, the new results, showed that, compared with the control arm, the combined low-dose CT screening arm had lower 10-year risks of dying from lung cancer (hazard ratio, 0.61; P = .02) and from any cause (HR, 0.80; P = .07).
In a landmark analysis restricted to individuals still alive and lung cancer free at 5 years, benefit of low-dose CT screening in reducing 10-year mortality was even greater, with sharply lower risks of dying from lung cancer (HR, 0.42; P = .0037) and from any cause (HR, 0.68; P = .01).
Analyses further showed that prevention of one lung cancer death required screening of 167 individuals with use of 733 low-dose CT scans and 4.4 PET scans.
In a landmark analysis restricted to individuals still alive and lung cancer free at 5 years, benefit of low-dose CT screening in reducing 10-year mortality was even greater,
The reduction in lung cancer mortality persisted in a sensitivity analysis that excluded the first 653 enrolled individuals to create a population receiving more homogeneous care (HR, 0.51; P = .049).
In additional trial findings, patients in the screening arm had a larger proportion of stage I tumors at detection (50.0% vs. 21.7%; P = .0004) and were more likely to undergo resection (65.3% vs. 26.7%, P less than .0001).
The investigators disclosed that they had no conflicts of interest. The trial was supported by the Italian Ministry of Health, the Italian Association for Cancer Research, Fondazione Cariplo, and the National Cancer Institute.
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