Title : Short- and long-term outcomes of neoadjuvant chemotherapy in operable locally advanced colon cancer: A systematic review
Abstract:
Background: Operable locally advanced colon cancer has traditionally been managed with upfront surgical resection followed by adjuvant chemotherapy when indicated. Neoadjuvant chemotherapy (NAC) may provide tumor downstaging, improve the likelihood of complete resection, and treat micrometastatic disease earlier.
Objective: To synthesize evidence on the short- and long-term outcomes of NAC in patients with operable locally advanced colon cancer, with emphasis on pathological response, surgical feasibility, perioperative morbidity and mortality, recurrence, disease-free survival (DFS), and overall survival (OS).
Methods: A systematic literature search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was conducted through October 2025 in accordance with PRISMA guidance. Eligible studies included randomized controlled trials and prospective or retrospective studies reporting relevant clinical outcomes in operable locally advanced colon cancer. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. Because of substantial heterogeneity in study populations, regimens, outcome definitions, and follow-up, findings were synthesized qualitatively rather than by meta-analysis.
Results: Twelve studies were included in the qualitative synthesis. Colon-cancer-specific studies reported pathological complete response rates ranging from 7.8% with FOLFOXIRI to 16% with FOLFOX. A phase II trial reported a 100% R0 resection rate with FOLFOXIRI and no 30- or 90-day postoperative mortality. In a large retrospective analysis, the survival effect of NAC was stage-dependent: a significant OS benefit was observed in T4 disease (HR 0.85), but not in T3 disease. In the FOxTROT-related analysis, biomarker-directed addition of panitumumab to FOLFOX in selected KRAS-wildtype patients was associated with significant improvements in DFS and OS. Evidence from rectal cancer studies included in the review suggested that preoperative chemotherapy can achieve outcomes comparable to neoadjuvant chemoradiotherapy in selected settings.
Conclusion: NAC appears to be a feasible and promising strategy for operable locally advanced colon cancer, particularly in T4 disease and when treatment is tailored to molecular characteristics. Its benefits are not uniform across all stages, and the current evidence supports careful patient selection. Future research should prioritize large randomized trials in well-defined high-risk populations, biomarker-driven treatment strategies, and total neoadjuvant approaches.
Keywords: colon cancer; locally advanced colon cancer; neoadjuvant chemotherapy; overall survival; pathological complete response; systematic review
