Prevalence and clinical outcomes of anaplastic lymphoma kinase rearrangements in surgically resected adenocarcinoma lung cancer: a retrospective cohort study.

BACKGROUND

The recent expansion of anaplastic lymphoma kinase (ALK)-targeted therapies into curative-intent settings is a major advance in the management of ALK-rearranged lung adenocarcinomas. However, real-world data on the prevalence and postoperative outcome reflecting this shift are needed to establish clinical baselines. This study aimed to characterize the prevalence, recurrence patterns, and prognostic factors of ALK-positive lung cancer in a modern surgical cohort.

METHODS

We conducted a single-center, retrospective cohort study of 5,783 patients with pathological stage I-III non-small cell lung cancer (NSCLC) who underwent curative-intent resection. Among the 3,288 patients with resected lung adenocarcinoma who underwent ALK testing, ALK prevalence and postoperative outcomes, including disease-free survival (DFS) and recurrence patterns, were evaluated. A multivariate Cox regression analysis was used to identify factors associated with recurrence.

RESULTS

ALK rearrangements were identified in 150 of 3,288 patients (4.6%). The median age was 56 years; 60.7% were never-smokers and 56.0% were female. Most patients had stage I disease (58.0%) and 30.0% had stage III disease. At a median follow-up of 45.7 months, the median DFS was not reached, and the 1-, 3-, and 5-year DFS rates were 93.3%, 77.6%, and 65.7%, respectively. N2 nodal involvement was the strongest independent predictor of recurrence [hazard ratio (HR), 14.64; 95% confidence interval (CI): 4.59-46.76; P<0.001]. Distant recurrence was predominant (81.1%), with the brain being the most frequent site (29.7%). Overall survival (OS) data were immature, with one death (0.7%) observed during follow-up.

CONCLUSIONS

ALK rearrangements represent a clinically meaningful subset of resectable lung adenocarcinomas, supporting routine molecular testing even in early-stage disease. Recurrence risk is primarily driven by nodal burden, particularly N2 disease, and is characterized by frequent distant and intracranial recurrences. These findings define the postoperative risk landscape of resected ALK-positive lung cancer and support CNS-active perioperative ALK-targeted strategies, particularly in patients with high-risk nodal disease.