Prognostic impact of ALK rearrangement in surgically treated stage I lung adenocarcinoma: a retrospective cohort study.

Background: Anaplastic lymphoma kinase (ALK) rearrangement is a key driver mutation in lung adenocarcinoma (LUAD). Despite its established role in advanced diseases, the prognostic impact of ALK rearrangement on early-stage LUAD remains unexplored. Therefore, we aimed to explore the prognostic value of ALK rearrangement in surgically treated stage I LUAD by analyzing patient demographics, tumor characteristics, recurrence, and therapy patterns. Methods: This retrospective study reviewed postoperative pathologic stage I LUAD patients who underwent ALK rearrangement testing at West China Hospital, Sichuan University. The prognostic impact of ALK rearrangement on recurrence-free survival (RFS), along with clinicopathologic features, mutational profiles, and targeted therapy patterns of ALK-positive patients, was assessed. Results: The cohort comprised 3,775 patients, of whom 165 (4.37%) were ALK-positive. ALK rearrangement rates were significantly higher in females (P=0.048), stage IB (P<0.001), and those without epidermal growth factor receptor (EGFR) mutations (P<0.001). ALK-positive tumors were more likely to exhibit high-risk radio-pathological features for recurrence, with the trend being more pronounced in stage IA cases. ALK-positive patients showed worse RFS compared to negative ones (log-rank P=0.009), but this difference did not remain significant in multivariable analysis [hazard ratio (HR) =1.72; P=0.09]. Further analysis revealed that ALK rearrangement was significantly associated with an increased risk of metastasis [odds ratio (OR) =2.15; P=0.045], particularly to the bone (OR =5.38; P<0.001) and brain (OR =2.88; P=0.041) after adjusting for confounders. Conclusions: ALK rearrangements were linked to more aggressive histology and increased risk of bone and brain metastases in resected, stage I LUADs, emphasizing the potential relevance of molecular profiling in postoperative risk assessment and treatment planning, even in stage IA patients.