Extended Lymphadenectomy for Right-Sided Colon Cancer: A Systematic Review and Narrative Synthesis of Evidence,...

Right-sided colon cancer represents a substantial portion of all colorectal malignancies worldwide. Extended lymphadenectomy techniques, such as complete mesocolic excision (CME) with central vascular ligation (CVL) and D3 lymph node dissection, aim to improve oncological outcomes through enhanced nodal harvest and dissection along embryological planes. Despite two decades of investigation and six prospective studies, the survival benefit remains unproven in unselected populations, and patient selection criteria remain poorly defined. This International Prospective Register of Systematic Reviews (PROSPERO)-registered systematic review (CRD420261334953) and structured narrative synthesis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four databases were searched through February 2026. Two independent reviewers screened records and assessed study quality using the Cochrane Risk-of-Bias 2 (RoB 2), Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2). Given the documented inability of seven published meta-analyses to resolve this question through statistical pooling, a structured narrative synthesis was performed. Fifty-five studies were included: four completed or interim-reported prospective trials, one ongoing randomized controlled trial (RCT), one international prospective observational cohort, seven systematic reviews and meta-analyses, and 42 comparative observational studies. Extended lymphadenectomy consistently increased lymph node yield across all prospective trials (Grading of Recommendations Assessment, Development and Evaluation (GRADE): low-certainty evidence). The only completed randomized trial with published primary survival data did not meet its primary disease-free survival (DFS) endpoint, although a non-significant trend favoring extended dissection was observed. Additional prospective studies from Germany, Russia, and Italy have not demonstrated a universal survival benefit. Intraoperative vascular injury was modestly increased with extended dissection (GRADE: moderate-certainty evidence), without a significant increase in overall complications or mortality. Exploratory, hypothesis-generating subgroup analyses from the largest trial identified a potential benefit in patients with advanced nodal disease and lymphovascular invasion; however, this finding requires prospective validation. Extended lymphadenectomy provides superior nodal harvest without a proven universal survival benefit. Current evidence supports an evidence-informed, stratified approach rather than a uniform policy: standard D2 dissection for cecal and early-stage ascending colon cancer and selective CME with CVL and D3 dissection for advanced-stage disease and for hepatic flexure or transverse colon tumors with high-risk features when performed in experienced centers. The proposed selection framework is interpretative and requires prospective validation. Mature survival data from ongoing trials are needed before definitive guideline recommendations can be made.