Lymph Node Ratio Is Associated with Time to Pulmonary Metastasis in Patients with Resected Colorectal Cancer

Abstract

INTRODUCTION: Despite curative resection for colorectal cancer (CRC), pulmonary metastasis (PM) may occur in up to 18% of cases. Among biomarkers that have been previously explored to inform CRC prognosis, Lymph Node Ratio (LNR) has been associated with shorter overall and disease-free survival in patients with resectable disease. We sought to investigate LNR from primary CRC pathology as a risk factor for overall development as well as time to development of PM. METHODS: A retrospective analysis of patients from prospectively maintained institutional thoracic and colorectal surgical databases (2000-2017) was performed. Patients were categorized based on whether they developed PM. LNR was defined as ratio of malignant nodes to total nodes harvested during primary colorectal resection. Multivariable Cox regression analysis (MVA) was performed to investigate the effect of LNR on time to PM diagnosis. RESULTS: 1600 patients were included in the analysis, among whom 233 (14.6%) were diagnosed with PM during follow-up. Patients without PM had median LNR of 0.00 (interquartile range [IQR]: 0.00 to 0.07), while patients who were diagnosed with PM had median LNR of 0.06 (IQR: 0.00 to 0.18). MVA controlling for clinicopathologic variables (Table) revealed LNR to predict time to PM diagnosis in CRC patients (hazard ratio: 14.93, 95% confidence interval: 6.13 to 36.37, p < 0.001). CONCLUSION: Elevated LNR is associated with both diagnosis and time to development of PM in patients with resectable CRC. As such, LNR should be considered during discussions of prognosis and recommendations for surveillance after primary CRC resection. Table. - Multivariable Cox Regression Analysis Investigating the Effect of Lymph Node Ratio on Pulmonary Metastasis development Clinicopathologic characteristics Hazard ratio (95% CI) p Value Lymph Node Ratio (Increasing) 14.93 (6.13-36.37) <0.001 Neoadjuvant Chemotherapy 1.44 (1.06-1.95) 0.020 Pathologic T Status >2 1.59 (1.05-2.38) 0.027 CRC Location Right Reference Left 1.74 (1.18-2.56) 0.005 Rectum 0.91 (0.58-1.43) 0.683 KRAS Mutated 5.62 (4.12-7.65) <0.001 Adjuvant Chemotherapy 5.68 (3.87-8.34) <0.001