Prognostic effect of sidedness in early stage versus advanced colon cancer

Background and Aims The prognostic effect of sidedness in colorectal cancer has been evaluated in numerous prospective and retrospective cohorts. Most of these have reported overall survival data; there is scant relapse-free survival data in early stage disease. This study aimed to determine the effect of tumor sidedness in survival in early stage and relapsed colon cancer. Methods Patients with stage I-III colorectal cancer were identified from the BC Cancer Agency Gastrointestinal Cancer Outcomes Unit. Survival analysis by stage and sidedness was compared with the log-rank test. Baseline characteristics were controlled by multivariate Cox-proportional hazard models. In relapsed patients, bevacizumab and EGFR inhibitor (EGFRI) treatments were included and tested for interaction. Results Among 5378 patients with stage I-III colon cancer, patients with right-sided stage II tumors experienced better relapse-free survival compared with those with left-sided tumors; right-sidedness was not prognostic for RFS in stage III disease. When survival was considered in patients who relapsed, right-sided tumors had inferior survival after relapse in both stage II and stage III tumors. At relapse, right-sided outcomes were inferior regardless of biologic therapy. An interaction test revealed a significant association between sidedness and survival with EGFRIs. Conclusions In this large, population-based study, right-sided presentation has a significant prognostic impact: in early stage, right-sidedness is favorably prognostic among stage II tumors and not prognostic in stage III disease. After relapse, right- sidedness is associated with an inferior prognosis, regardless of initial stage of presentation. Colon tumor sidedness is independently prognostic and may be considered in treatment assignment for both early stage and advanced disease.