Roberta Eufrasia Ledda, Federica Sabia, Kyongmin Sarah Beck, Gianluca Milanese, Margherita Ruggirello, Maurizio Balbi, Luigi Rolli, Mattia Boeri, Gabriella Sozzi, Nicola Sverzellati, Alfonso Vittorio Marchianò, Ugo Pastorino
Lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces mortality through early-stage detection, yet evidence on long-term effectiveness and adherence remains limited. This study reports nearly 10-year outcomes from the prospective BioMILD trial, which enrolled 4,119 heavy smokers undergoing risk-adapted screening with LDCT. Participants were stratified by baseline LDCT results into LDCT + and LDCT - groups, and the latter were sent to triennial intervals. Over a median follow-up of 9.4 years (38,676 person-years), 248 LCs were diagnosed (6.0 %), with significantly higher incidence in the LDCT + group (21.8 % vs 3.0 %, p < 0.0001). Early-stage disease predominated across all four screening intervals (0-2, 3-5, 6-9, and ≥ 9 years), with stage I proportions consistently around or above 50 %. Ten-year all-cause and LC mortality were significantly higher in the LDCT + group (14 % and 5 %) compared to the LDCT - group (6 % and 1 %) (p < 0.0001). Screening adherence remained high at 3-5 years (92 %) and acceptable beyond 9 years (58 %), with no group differences. Baseline LDCT effectively stratified long-term risk, with over seven-fold higher LC incidence in LDCT + participants. However, LC cases continued to emerge in the LDCT - group, indicating that a negative baseline LDCT does not eliminate long-term risk. Despite differing risk profiles, screening maintained a consistent ability to detect early-stage LC across groups. In conclusion, long-term risk-adapted LDCT screening in the BioMILD trial sustained early-stage LC detection and acceptable adherence over nearly a decade, supporting continued surveillance even among initially low-risk individuals.