Prognostic Impact of ALK Rearrangements in Resected NSCLC: A Systematic Review and Meta-analysis

Background/Aim: ALK receptor tyrosine kinase (ALK) rearrangements occur in 4-8% of non-small cell lung cancer (NSCLC) and are often associated with aggressive clinical behavior. Although ALK-targeted tyrosine kinase inhibitors significantly improve overall survival in advanced-stage NSCLC, their role in early-stage disease remains unclear. This meta-analysis (PROSPERO CRD420251012874) aimed to systematically evaluate recurrence rates and disease-free survival (DFS) outcomes in surgically resected patients with ALK-rearranged NSCLC compared to ALK-wild type (WT). Patients and Methods: We conducted a systematic literature review according to PRISMA 2020 guidelines. Eligible studies included patients with surgically resected NSCLC with reported recurrence rate and DFS. Pooled recurrence rates, hazard ratios (HRs) for DFS, and recurrence patterns were analyzed using random effects models. Results: Fifteen studies encompassing 4,776 patients (630 ALK-rearranged and 4,146 ALK-WT) were included. The pooled recurrence rates were 40.2% and 30.2% for ALK-rearranged and ALK-WT patients, respectively. ALK-rearranged patients demonstrated a trend toward increased recurrence risk (risk ratio=1.20; 95% confidence interval=0.98-1.49; p=0.084) and significantly reduced DFS (HR=1.42; 95% confidence interval=1.08-1.88; p=0.013), particularly within 3 years follow-up and stage I subgroups. Furthermore, patients with ALK-rearranged NSCLC experienced significantly higher rates of systemic (RR, 1.32; p=0.027) and brain metastases (RR=1.71; p=0.046). Conclusion: Surgically resected ALK-rearranged NSCLC involves an increased risk of recurrence and reduced DFS, notably within the first 3 years, accompanied by higher rates of systemic and brain metastases. These findings underscore the importance of tailored postoperative surveillance strategies and suggest the potential role of perioperative ALK-tyrosine kinase inhibitors.