Evaluating the Impact of Induction and Consolidation Total Neoadjuvant Therapies Compared to Conventional Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Network Meta-analysis

BACKGROUND: Total neoadjuvant therapy has been introduced to enhance oncological outcomes and minimize toxicity in locally advanced rectal cancer, with the superiority between the induction and consolidation of therapy remains unclear. OBJECTIVE: Evaluate oncological and postoperative outcomes by comparing induction chemotherapy and consolidation chemotherapy with conventional chemoradiotherapy in patients with locally advanced rectal cancer. DATA SOURCES: Systematic searches of PubMed, Embase, and Cochrane databases were performed for studies published from their inception until June 2023. STUDY SELECTION: The inclusion criteria: patients diagnosed with rectal cancer, interventions including induction chemotherapy and consolidation chemotherapy, comparisons were specified as conventional neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES: Primary outcomes were the rates of pathological or clinical complete response, postoperative results, chemoradiotherapy-related toxicity, and survival outcomes. RESULTS: Thirty-three studies, encompassing patients from 1991 to 2021, were eligible for analysis. In network meta-analysis, a significantly increased odds ratio for a pathologic complete response was observed in both induction therapy group at 1.65 (95% CrI 1.18–2.30) and the consolidation therapy group at 1.87 (95% CrI 1.40–2.47) compared to conventional chemoradiotherapy. However, no difference was observed in complete response rates, postoperative results, or chemoradiotherapy-related toxicity ≥ 3 between the groups. There were no differences among the groups in local recurrence, distant metastasis, or disease-free survival, while the induction group showing a non-significant improvement in overall survival. LIMITATIONS: There was significant heterogeneity among the studies and the short follow-up period in most studies limits the assessment of long-term survival outcomes. CONCLUSIONS: Both induction and consolidation total neoadjuvant therapy increase the pathologic complete response rate in locally advanced rectal cancer without compromising safety or postoperative outcomes. However, total neoadjuvant therapy was not associated with a significant improvement in survival outcomes. While total neoadjuvant therapy strategies for locally advanced rectal cancer are considered safe, additional long-term studies are needed. REGISTRATION NO: CRD42023445348