Lung cancer screening benefits increase over time
medwireNews: The Multicentric Italian Lung Detection (MILD) study findings indicate that extending lung cancer screening beyond 5 years boosts the survival benefits associated with early disease detection.
Following the success of the US National Lung Screening Trial, which demonstrated a 20% reduction in lung cancer mortality with a 3-year program of annual low-dose computed tomography (LDCT), the MILD investigators hypothesized that a prolonged screening period might increase this benefit.
They now report 10-year MILD results in the Annals of Oncology, demonstrating a 39% reduction of lung cancer mortality with screening and “providing new evidence that extended intervention enhances the benefit of screening, notwithstanding biennial rounds and active surveillance.”
Ugo Pastorino (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) and team recruited 4099 volunteers aged 49–75 years to the study, all of whom were current smokers or had quit smoking within the past 10 years, and had at least 20 pack–years.
The participants were randomly assigned to undergo LDCT lung screening (n=2376) or no intervention (n=1723); the screening arm underwent a further randomization process to undergo LDCT every 12 months (n=1190) or 24 months (n=1723).
Participants received annual or biennial screening for a median of 6.2 years, with 93.5% of the 3856 study survivors achieving 9 years of follow-up and 71.0% completing 10 years, the researchers say.
Lung cancer was detected in 98 screened patients and 60 controls, giving a rate of 413 versus 373 cases per 100,000 person–years. The researchers calculated that 154 LDCT and 1.4 positron emission tomography (PET) scans, used selectively for differential diagnosis, were required to identify one case of lung cancer.
Among the patients diagnosed with lung cancer, those in the screening arm were significantly more likely to have stage I disease at time of detection than individuals in the control arm (50.0 vs 21.7%) and were significantly more likely to undergo resection (65.3 vs 26.7%).
The MILD protocol was designed to allow active surveillance of subsolid lesions, allowing “a safe strategy for slow growing nodules” that risk overdiagnosis and overtreatment of lung adenocarcinoma, the researchers explain.
They report that active surveillance and PET differential diagnosis successfully reduced the risk for unnecessary surgery in the intervention arm, with minor resection for benign disease occurring in a comparable 4.5% and 5.9% of the screening and control arms, respectively.
The 10-year risk for overall mortality was 5.8% with screening versus 6.5% without intervention, translating to a significant hazard ratio (HR) of 0.80 in favor of LDCT. Moreover, the 10-year risk for lung cancer mortality was 1.7% versus 2.5%, giving a HR of 0.61.
Landmark analysis beyond 5 years confirmed that the risk for overall and lung cancer mortality was significantly reduced with screening versus no screening, with HRs of 0.68 and 0.42, respectively.
And this was confirmed in a sensitivity analysis including a “more homogeneous” group of 3446 individuals, which gave a significant 49% reduction in lung cancer mortality with screening beyond 5 years despite having lower statistical power.
The MILD investigators say their results “provide indirect evidence that tailored biennial LDCT did not compromise the efficacy of prolonged screening duration, but this issue will require future confirmation by a multicentric randomized trial with adequate sample size.”
The bioMILD trial will now investigate a triennial screening approach for patients with a negative LDCT at baseline, they add.
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