Prognostic and Predictive Value of Lymph Node Ratio in Stage III Colon Cancer in the Era of Molecular Biomarkers

Background: The prognostic and predictive value of the lymph node ratio (LNR; metastatic/harvested nodes) in stage III colon cancer (CC) remains unclear, particularly in combination with molecular profiles such as RAS, BRAF, and microsatellite instability (MSI) status.Methods: We retrospectively analyzed stage III CC patients who underwent curative resection with D3 lymph node dissection (2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021)(2022)(2023).Optimal LNR cutoffs were determined using maximally selected rank statistics.Cox models assessed the prognostic impact of LNR adjusted for clinicopathological and molecular factors.The effect of adjuvant chemotherapy (ACT) on recurrence-free (RFS) and overall survival (OS) was evaluated by LNR subgroup.Results: Among 361 patients, optimal LNR cutoffs for RFS and OS were 0.16 and 0.21, respectively.Based on the cutoffs of 0.2, the RFS and OS were longer in patients with low LNR than those with high LNR.Multivariate analysis identified RAS and BRAF mutation, venous invasion, LNR and ACT as independent factors for RFS, while RAS mutation, lymphatic invasion, ACT and LNR were significant for OS.In patients with low LNR (! 0.2), ACT improved RFS (HR 0.57 (95% CI 0.33-0.99))and OS (HR 0.48 (95% CI 0.28-0.85))and similar tendency was observed in those with high LNR (>0.2) (RFS: HR 0.56 (95% CI: 0.29-1.09),OS: HR 0.51 (95%CI 0.23-1.13)).Conclusion: After adjustment for multiple biomarkers, LNR remained an independent predictor of OS in stage III CC.ACT was associated with improved survival regardless of LNR, with a consistent trend observed even in patients with high LNR.