Predictive and prognostic factors in patients with Anaplastic Lymphoma Kinase: rearranged early-stage lung adenocarcinoma

Abstract OBJECTIVES This study aimed to evaluate the predictive and prognostic factors in clinical stage I, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients. METHODS A multicentric, retrospective, case–control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy. Data were collected from 5 high-volume oncological centres. An external cohort of ALK wild-type patients was also analysed for comparison. Survival analyses were performed using the Kaplan–Meier method, and multivariable Cox regression analysis was used to identify prognostic factors. RESULTS From January 2016 to December 2022, 63 patients with ALK-rearranged lung adenocarcinoma were included. High-grade tumours (G3) significantly associated with upstaging (odds ratio = 3.904, P = 0.04). Disease-free survival (DFS) and overall survival were significantly improved in upstaged patients receiving adjuvant treatment [hazard ratio (HR) = 0.18, P = 0.0042; HR = 0.24, P = 0.0004, respectively]. The solid or micropapillary histological subtypes were independently associated with worse DFS (HR = 3.41, P = 0.022). Comparison with 435 ALK wild-type patients showed worse DFS in the ALK-rearranged group (HR = 2.09, P = 0.0003). ALK-rearranged patients had higher rates of nodal upstaging, systemic and brain recurrences. CONCLUSIONS Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumours are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and overall survival in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort.