Association between lymphovascular invasion and lymph node metastases in colon cancer: A National Cancer Database analysis.

Objective: Lymphovascular invasion (LVI) is a well-known risk factor in colorectal cancer that is associated with a worse prognosis. The present study aimed to assess the characteristics of patients with LVI-positive colon cancer according to the status of nodal metastases and to study the association between LVI-nodal status and survival.

Methods: This retrospective study assessed the association between LVI and lymph node metastases in colon cancer, using data from the National Cancer Database. Patients were classified according to the pathological N stage into pN0 and pN1-2. The risk factors for LVI were determined in each group using multivariable regression analyses. The primary outcome was LVI and the secondary outcome was 5-year overall survival (OS). A modification of the tumour, node, metastasis (TNM) staging system that incorporates LVI in each stage was proposed.

Results: The study included 357 724 patients (51.1% female, median age 70 years). LVI was detected in 11.6% and 52.5% of patients with node-negative and node-positive disease, respectively. The independent predictors of LVI in pN0 stage were poorly differentiated carcinomas (OR: 3.6, p < 0.001), undifferentiated carcinomas (OR: 3.3, p < 0.001), mucinous carcinomas (OR: 0.61, p < 0.001), and perineural invasion (OR: 4.2, p < 0.001). The independent predictors of LVI in pN1-2 disease were poorly differentiated carcinomas (OR: 2.36, p < 0.001), undifferentiated carcinomas (OR: 3.23, p < 0.001), and perineural invasion (OR: 3.33, p < 0.001). LVI was significantly associated with worse 5-year OS and the adverse survival impact of LVI was higher in pN1-2 disease (HR: 1.47, p < 0.001) than in pN0 disease (HR: 1.28, p < 0.001). When LVI was present, the 5-year OS was reduced by 1.5% in stage I, 5.6% in stage II, and 11.5% in stage III.

Conclusions: LVI was more prevalent in patients with colon cancer with lymph node metastases than in patients with node-negative disease. However, LVI was not detected in approximately half of patients with nodal disease. The adverse survival effect of LVI was proportional to the stage of colon cancer.