Abstract 7409: Effectiveness of lung cancer screening by sex and tumor histology: Extended, pooled analysis of the ITALUNG and LUSI trials, with comparison to findings in the NLST

Abstract Introduction: Low-dose computed tomography (LDCT) screening can reduce lung cancer (LC)-related mortality, but questions remain about the duration of this effect and differences by sex and tumor histology. Methods: Extended follow-up data from the ITALUNG and LUSI trials were pooled to examine screening-related tumor stage-shifts and to estimate relative hazards for LC-related mortality, by sex and histology. Findings were compared to, and additionally combined with, those from the US National Lung Screening Trial (NLST). Results: In ITALUNG-LUSI, screening yielded a 30% reduction of overall LC mortality up to 8 years after final screening (dilution-adjusted HR=0.70[0.51-0.96]). This reduction, however, was more pronounced for women (HR=0.49[0.25-0.96]) than men (HR=0.78[0.54-1.11]), which was confirmed in combined data of ITALUNG-LUSI plus NLST (6 years post-screening, women: HR=0.74[0.61-0.90], men: HR=0.93[0.80-1.06]; pheterogeneity=0.06). Analyses of stage-shifts and relative mortality hazards suggested that screening reduced mortality by non-small cell and non-squamous tumors in both sexes. In women (18-20%), more than among men (5-9%), screening also resulted in frequent detection of adenocarcinomas with lepidic growth. Finally, in both ITALUNG-LUSI and NLST, LDCT screening reduced the incidence and mortality for small-cell lung cancer (SCLC) among women (HR=0.63[0.43-0.94], all trials combined) but not among men (pheterogeneity=0.04). Conclusion: LC-related mortality reduction by LDCT screening may last until 8 or more years after cessation, and appears to be stronger for women than men, due to reduced incidence and mortality of SCLC in women only. The latter might be caused by removal of (likely EGFR-mutated, and slowly growing) adenomatous precursor lesions that over time would transform into SCLC (lineage plasticity). These findings may have major implications for the optimization of screening programs in terms of eligibility criteria and screening intervals Citation Format: Rudolf Kaaks, Francisco O. Cortès-Ibañez, Stefan Delorme, Erna Motsch, Verena Katzke, Claus-Peter Heussel, Hans-Ulrich Kauczor, Giulia Picozzi, Giuseppe Gorini, Francesca Maria Carozzi, Laura Carrozzi, Eugenio Paci, Donella Puliti, Mario Mascalchi. Effectiveness of lung cancer screening by sex and tumor histology: Extended, pooled analysis of the ITALUNG and LUSI trials, with comparison to findings in the NLST [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7409.