# Short- and Long-Term Outcomes of Neoadjuvant Chemotherapy in Operable Locally Advanced Colon Cancer: A Systematic Review

## TL;DR

This review examines the effectiveness of neoadjuvant chemotherapy for advanced colon cancer, finding it beneficial for certain stages and when combined with targeted therapies.

## Contribution

The study provides a systematic synthesis of short- and long-term outcomes of neoadjuvant chemotherapy in operable locally advanced colon cancer.

## Key findings

- NAC achieved up to 16% pathological complete response with FOLFOX-based regimens.
- NAC showed significant overall survival improvement specifically in T4 colon cancer.
- Biomarker-directed therapies improved disease-free and overall survival in selected patients.

## Abstract

The management of operable locally advanced colon cancer has traditionally centered on upfront surgical resection. The role of neoadjuvant chemotherapy (NAC) in this setting remains a subject of investigation, with potential benefits including tumor downstaging and early treatment of micrometastases. This systematic review aims to synthesize the existing evidence on the short- and long-term outcomes of NAC for patients with operable locally advanced colon cancer. A systematic literature search was conducted across PubMed/MEDLINE, Embase, Scopus, and Web of Science up to October 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting on pathological response, surgical outcomes, recurrence, disease-free survival (DFS), or overall survival (OS) in patients receiving NAC for locally advanced colon cancer were included. The risk of bias was assessed using the Cochrane RoB 2 tool for randomized trials and the ROBINS-I tool for non-randomized studies. A qualitative synthesis was performed due to heterogeneity among the included studies. Twelve studies were included. Pathological complete response rates varied, reaching up to 16% with FOLFOX-based regimens in colon cancer. NAC was associated with high R0 resection rates and acceptable postoperative morbidity. A key finding was the stage-dependent survival benefit, with a significant OS improvement specifically in T4 disease but not in T3 disease. The addition of targeted therapy based on biomarker status (e.g., panitumumab in KRAS-wildtype tumors) demonstrated significant improvements in DFS and OS. Evidence from rectal cancer studies suggested that NAC could achieve outcomes comparable to neoadjuvant chemoradiotherapy. NAC is a feasible and effective strategy for operable locally advanced colon cancer, demonstrating significant pathological responses and promising survival outcomes, particularly in T4 tumors and with biomarker-directed therapy. Its efficacy is highly dependent on careful patient selection based on disease stage and molecular characteristics. Future research should focus on randomized trials in high-risk populations and the integration of personalized treatment approaches.