Extended lung cancer (LC) screening with low-dose computed tomography (LDCT) decreased 10-year mortality rates in a large cohort of Italian smokers, according to the results of a prospective, randomized, controlled screening trial published in the Annals of Oncology.
“The National Lung Screening Trial showed that [LC] screening by three annual rounds of [LDCT] reduces LC mortality,” wrote the authors, led by Ugo Pastorino, MD, Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. “We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years.”
In the Multicentric Italian Lung Detection (MILD) trial, Dr. Pastorino and colleagues prospectively randomized 4,099 participants to either an LDCT screening group (n=2,376) or a control group (n=1,723) with no intervention. The screening arm was further randomized into those who received annual screening (n=1,190) and those who received screening every 2 years (n=1,186). Primary endpoints included 10-year overall and LC-specific mortality. Landmark analysis was employed to test the long-term effect of LC screening (> 5 years).
The LDCT arm demonstrated a 39% decreased risk of LC mortality at 10 years (HR: 0.61; 95% CI: 0.39–0.95) vs the control arm. The LDCT arm also showed a 20% reduction in overall mortality (HR 0.80; 95% CI: 0.62–1.03) vs the control arm.
LDCT benefit was enhanced after the fifth year of screening, yielding a 58% reduced risk of LC mortality (HR 0.42; 95% CI: 0.22–0.79), as well as a 32% decrease in overall mortality (HR 0.68; 95% CI: 0.49–0.94).
The investigators found that the median duration of screening for LDCT was 6.2 years. They diagnosed LC in 98 participants (431/100,000 person-years) in the intervention arm vs 60 participants (373/100,000 person-years) in the control arm.
On landmark analysis beyond 5 years, Dr. Pastorino et al found a 3.4% cumulative risk of overall mortality in the intervention arm compared with 4.5% in the control arm, with a significant 32% (95% CI: 6% to 51%) risk reduction due to LDCT (HR: 0.68; 95% CI: 0.49–0.94; P=0.01)
The MILD study was originally designed to analyze the effects of prolonged LDCT screening past 4 years in a sample of adults aged 49-75 years with either ≥ 20 pack-years for current smokers or < 10 pack-years for former smokers. These subjects had no history of cancer in the past 5 years. Furthermore, MILD study investigators used positron emission tomography and active surveillance of subsolid lesions to limit unnecessary surgery, which—according to the authors—was a strength of the study.
Upon early analysis of the MILD trial, previous investigators found no mortality reduction in the LDCT arm at 5 years, and a comparable performance of annual vs biennial LDCT, with respect to detection rates and interval cancers, at 7 years. In the current study, Dr. Pastorino and fellow researchers reported the 10-year results of MILD, with a focus on overall and LC mortality.
“The MILD trial provides additional evidence that prolonged intervention beyond 5 years can enhance the benefit of screening,” concluded the authors. “The incremental effect of prolonged LC screening achieved a significant mortality reduction at 10 years, notwithstanding biennial rounds and active surveillance.”