In the phase 3 NeoCol randomized clinical trial of 248 patients with CT-staged locally advanced colon cancer, neoadjuvant capecitabine plus oxaliplatin did not improve 3-year disease-free survival compared with upfront surgery (83% vs 87%). Overall survival, surgical outcomes, adverse events, and quality of life were similar between groups. Neoadjuvant therapy achieved tumor downstaging and reduced the proportion of patients requiring adjuvant chemotherapy but did not confer a survival advantage.