Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation.

TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.