Clinicopathologic Predictors of Outcome and Implications for Adjuvant Therapy in Pathologic Stage II Non-small Cell Lung Cancer

Background/Aim: Pathologic stage II non-small cell lung cancer (NSCLC) exhibits heterogeneous outcomes despite curative resection. Although adjuvant EGFR-TKI and immunotherapy have improved survival in resected NSCLC, subgroup analyses from major trials show only modest benefit in stage II disease. Given these limited gains and the variable cost-effectiveness of adjuvant therapy across regions, identifying prognostic factors is essential to guide treatment decisions and support value-based precision care. Patients and Methods: We retrospectively analyzed 115 patients with pathologic stage II NSCLC (27 IIA, 88 IIB) who underwent complete resection at a tertiary hospital in Taiwan (2016-2023). Clinicopathologic variables–including histologic subtype, spread through air spaces (STAS), and lymphovascular invasion (LVI) – were reviewed. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox proportional hazards analyses. Results: The 5-year RFS and OS rates were 50.9% and 67.9%, respectively. Independent predictors of recurrence included tumor size >4 cm [hazard ratio (HR)=2.88, p=0.008], N1 nodal status (HR=3.20, p=0.016), and high-risk adenocarcinoma subtype (micropapillary/solid; HR=2.80, p=0.014). Adjuvant chemotherapy significantly improved OS (76.4% vs. 37.2%, p=0.002). Conclusion: Tumor size, nodal involvement, and histologic subtype are key prognostic determinants in stage II NSCLC. Identifying high-risk patients is crucial to optimize selection for adjuvant immunotherapy or targeted therapy and to ensure clinical and economic benefit.