Researchers have found in a negative trial that neoadjuvant chemotherapy did not improve disease-free survival compared with upfront surgery. However, along with other phase III studies, the findings suggest it may still have a role in the individualized management of patients with locally advanced colon cancer. Locally advanced colon cancer carries a high risk of recurrence. Neoadjuvant chemotherapy has been proposed to improve outcomes, but evidence from phase III trials remains limited.A study was done to determine whether neoadjuvant chemotherapy improves disease-free survival (DFS) compared with upfront surgery in patients with locally advanced colon cancer. This randomized, open-label, phase III clinical trial conducted from October 14, 2013, to November 27, 2020, with follow-up up to 3 years for disease-free survival took place at 9 hospitals in Denmark, Norway, and Sweden. A total of 250 patients with locally advanced colon cancer staged by computed tomography, Eastern Cooperative Oncology Group performance status 0 to 2, and no distant metastases were enrolled. These data were analyzed from January 2024 to October 2024. Patients were randomized 1:1 to upfront surgery followed by adjuvant chemotherapy as indicated (n = 122) or 3 cycles of neoadjuvant capecitabine and oxaliplatin followed by surgery and adjuvant chemotherapy if indicated (n = 126).The primary end point was disease-free survival . Secondary end points included surgical and pathological outcomes, adjuvant chemotherapy use, adverse events, quality of life, and exploratory analysis by mismatch repair (MMR) status. Results A total of 248 patients were eligible and included in analyses (median age, 66 [min-max, 24-84] years; 111 women [45%] and 137 men [55%]). At 3 years, disease-free survival was 87% in the upfront surgery arm and 83% in the neoadjuvant arm (P = .36). Neoadjuvant chemotherapy was feasible and safe, achieved tumor downstaging, and reduced the proportion of patients meeting criteria for adjuvant chemotherapy (upfront surgery 73% vs neoadjuvant group 59%; P = .02). Exploratory analyses suggested variation by MMR status, with disease-free survival estimates higher after upfront surgery in patients with MMR-deficient tumors. Postoperative complications, adverse event profiles, and quality of life were comparable between groups.Neoadjuvant chemotherapy did not improve disease-free survival compared with upfront surgery, establishing the NeoCol trial as negative. However, feasibility, safety, downstaging effects, reduced adjuvant chemotherapy use, and MMR subgroup findings add to evidence from other randomized trials supporting further evaluation of this strategy in individualized management of locally advanced colon cancer.Reference:Jensen LH, Kjaer M, Diness LV, et al. Neoadjuvant Chemotherapy vs Upfront Surgery in Patients With Locally Advanced Colon Cancer: A Randomized Clinical Trial. JAMA Surg. Published online March 04, 2026. doi:10.1001/jamasurg.2026.0085Keywords:Neoadjuvant, Chemotherapy, Superior, Upfront, Surgery, Colon Cancer, JAMA, Jensen LH, Kjaer M, Diness LV