Increased Risk of Central Mesocolic Lymph Node Metastases in BRAF-Mutated Stage I-III Colon Cancer

Background: The optimal extent of lymphadenectomy in colon cancer (CC) remains controversial. While Complete Mesocolic Excision (CME)/D3 dissection may improve oncological outcomes, the survival benefit appears limited to patients with central lymph node metastases (LNMs). Molecular profiling could help identify patients who may benefit from extended lymphadenectomy. Methods: This prospective cohort sub-study of the international T-REX trial included 97 patients with stage I-III CC who underwent curative resection at the National Cancer Centre, Vilnius, Lithuania (2015-2018). Lymph node mapping was performed by anatomical zones, and BRAF and KRAS mutation status in primary tumors was determined by quantitative PCR. Associations between genetic mutations, LNM distribution, and survival outcomes were analyzed. Results: A total of 2710 lymph nodes were retrieved from 97 patients, of which 100 (3.7%) were metastatic, and identified in 33 (34.0%) patients. Central LNMs were observed in 5 (5.2%) patients overall but were significantly more frequent among those with BRAF-mutated tumors (30.8%) compared to KRAS-mutated (2.4%) or wild-type (0%) cases (p < 0.001). BRAF mutations were associated with increased odds of intermediate (OR 8.1, 95% CI 1.4-45.6) and central (OR 36.8, 95% CI 3.7-366.7) LNMs. Mutation status did not impact overall or disease-free survival. Conclusions: BRAF mutations in primary CC are linked to higher rates of intermediate and central LNMs. Patients with BRAF-mutated tumors may benefit from extended lymphadenectomy. Future randomized trials should evaluate biomarker-driven surgical strategies in CC.