Neoadjuvant Radiation Versus Upfront Surgery for Upper Rectal Cancer: A Systematic Review and Meta-Analysis of the Evidence.

INTRODUCTION: Neoadjuvant radiation therapy (NRT) is a cornerstone in the treatment of lower and middle rectal cancers. However, the efficacy of NRT in upper rectal cancer remains debated due to conflicting recommendations and study outcomes. This study aims to re-evaluate the effects of NRT versus upfront surgery in upper rectal cancer through a comprehensive systematic review and meta-analysis of recent and relevant studies. METHODS: A systematic search was conducted in Ovid Medline, PubMed, Embase, Scopus, Cochrane Central, and Clinicaltrials.gov, filtering studies published from January 2002 onward to reflect contemporary treatment paradigms. We included randomized controlled trials and observational studies comparing outcomes between NRT and upfront surgery in upper rectal cancer. The primary outcomes were overall survival (OS) and local recurrence (LR). RESULTS: Thirteen studies met the inclusion criteria, comprising three randomized controlled trials and ten observational studies. Meta-analysis showed no statistically significant improvement in OS with NRT (risk ratio: 0.92, 95% confidence interval, 0.83-1.02), but a significant reduction in LR risk (risk ratio: 0.63, 95% confidence interval, 0.43-0.95). CONCLUSIONS: NRT does not significantly improve OS for upper rectal cancer patients but can reduce the risk of LR in select patients. These findings suggest a selective use of NRT in higher risk upper rectal cancers, especially considering potential adverse effects and the anatomical challenges in defining upper rectal cancer. The analysis was limited by the heterogeneity of study designs and the retrospective nature of most included studies.