Sidedness and Molecular Pattern in Defining the Risk of Lymph Node Metastasis in Nonmetastatic Colorectal Cancer: Single-Center Retrospective Study

<b>Background</b>: Lymphadenectomy plays a central role in the treatment of localized colon cancer. While in left colon cancer the D3 lymphadenectomy/CME is considered the standard of care, lymphatic stations to be removed in right colon cancer are still a matter of discussion. The individuation of LNM risk factors could help in choosing the lymphadenectomy in right-sided tumors. This study aims to analyze the correlation of histopathological and molecular characteristics with lymph node metastasis, both in right- and left-sided colon cancer, and their impact on survival; <b>Methods</b>: We conducted a single-center observational retrospective study. The following data were collected and analyzed for each patient: demographics, histopathological and molecular data, and intraoperative and perioperative data. Statistical analyses were performed, including descriptive statistics, multivariate logistic regression and survival analysis; <b>Results</b>: An association between tumor size (pT, <i>p</i> < 0.001), grading (<i>p</i> = 0.013), budding (<i>p</i> < 0.001), LVI (79,4% <i>p</i> < 0.001) and LNM was observed. A multivariate analysis identified pT4 (OR 5.45, <i>p</i> < 0.001) and LVI+ (OR 10.7, <i>p</i> < 0.001) as significant predictors of LNM. Right-sided patients presented a worse OS when associated with LNM, while no significant difference was observed in N0 patients; <b>Conclusions</b>: histological and molecular analysis can help identify high risk patients, which could benefit from extended lymphadenectomies. These patients could be ideal candidates for the D3 lymphadenectomy/CME.