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

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Background Contemporary 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. Methods PubMed, 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 I 2 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. Results Five 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. Conclusion In 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.

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