Upfront Total Mesorectal Excision for MRI-Defined Low-Risk cT3 Rectal Cancer: A Systematic Review and Meta-Analysis

BackgroundContemporary rectal cancer management increasingly relies on MRI-based risk stratification to identify low-risk cT3 tumors that may avoid neoadjuvant therapy. This meta-analysis compared upfront total mesorectal excision with neoadjuvant therapy in MRI-defined low-risk cT3 rectal cancer.MethodsPubMed, Scopus, and Cochrane Central were systematically searched through June 2025. Pooled odds ratios (ORs), mean differences (MDs), and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed with the I² statistic. Analyses were performed using R (version 4.4.2). A complementary Bayesian random-effects meta-analysis was performed to explore posterior uncertainty and potential equivalence between strategies.ResultsFive studies, including 1447 patients, were analyzed. Upfront surgery was associated with shorter operative time (MD -25.7 min; 95% CI -38.6 to -12.7) and more lymph nodes retrieved (MD 6.6; 95% CI 6.0-7.3). No significant differences were observed in perioperative complications, including anastomotic leaks, intra-abdominal abscesses, or reoperations. Oncologic outcomes were comparable, including circumferential resection margin positivity (CRM+) (OR 1.05; 95% CI 0.49-2.26), local recurrence (OR 0.99; 95% CI 0.58-1.70), and distant recurrence (OR 1.03; 95% CI 0.64-1.65). Survival outcomes were also similar, with no differences in disease-free (DFS) or overall survival (OS). Bayesian analyses supported these findings, with effect estimates centered around the null and probabilities of superiority close to equipoise, indicating inconclusive evidence.ConclusionIn MRI-defined low-risk cT3 rectal cancer, upfront TME may provide oncologic outcomes comparable to neoadjuvant therapy. However, the available evidence remains exploratory and insufficient to support definitive treatment recommendations.