Abstract Objectives While anaplastic lymphoma kinase (ALK) inhibitors have undergone rapid advancement, the prognostic impact of ALK fusion during the tumor progression without targeted therapy remains underexplored. This study comprehensively investigated the prognostic role of ALK fusion in resected lung adenocarcinoma (LUAD) stratified by stages, radiologic, pathologic and aggressive characteristics. Methods This study retrospectively collected entire clinic features and follow-up data of resected LUAD patients with ALK examation from 2008 to 2020. In survival analyse, patients who received tyrosine kinase inhibitor (TKI) therapy were excluded. Cases were categorized into following groups: “stage I” versus “stage II-III”, “part-solid” versus “solid”, “moderately-differentiatied” (including papillary, acinar or invasive mucinous adenocarcinoma) versus “poorly-differentiated” (including micropapillary or solid adenocarcinoma), “passive” versus “aggressive” (defined by the lymphovascular invasion, visceral pleural invasion or spread through air spaces) groups. Outcomes for ALK-postive and ALK-negative patients were evaluated within each group. Results Among 2766 cases, 135 (4.8%) were ALK-positive, which was significantly associated with younger age, advanced-stage, radiologic solid nodule, histologic solid type, lymphovascular invasion and spread through air spaces. No recurrence was observed during follow-up among patients who received ALK-TKIs. ALK fusion was correlated with reduced recurrence-free survival (RFS) and overall survival (OS) in stage I, part-solid, moderately-differentiatied and passive groups. In contrast, ALK-positive and ALK-negative patients exhibited comparable RFS and OS in stage II-III, solid, poorly-differentiated and aggressive groups. Furthermore, ALK fusion was an independent prognostic factor in stage I, part-solid, and passive groups. In stage II-III cohort, adjuvant chemotherapy was an independent prognostic factor for ALK-positive patients, but not for ALK-negative patients. Conclusions The independent prognostic value of ALK fusion in early-stage lung adenocarcinoma was demonstrated. In advanced-stage lung adenocarcinoma, ALK-positive status linked to greater survival benefits from adjuvant chemotherapy. This abstract is funded by: 1·3·5 project for disciplines of excellence from West China Hospital of Sichuan University (ZYGD23010 to LXL）
Ma et al. (2026) studied this question.