Different neoadjuvant therapies for locally advanced rectal cancer: A systematic review and network meta-analysis.

One of the historical standard of care for locally advanced rectal adenocarcinoma (LARC) is neoadjuvant fluoropyrimidine-based chemoradiotherapy (FP-based CTRT) followed 6-8 weeks later by surgery. The incorporation of further chemotherapy cycles (CT) before or after CTRT (total neoadjuvant therapy) resulted in better outcomes than CTRT alone. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for LARC. Fixed-or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) or risk ratios (RRs) with 95 % credible intervals (95 % CrIs). A total of 23 randomized clinical trials were included. In Bayesian comparisons. FOLFIRINOX followed by capecitabine-based CTRT resulted in better OS than other regimens, including the previous standard, and ranked as the best regimen with a probability of 87 %. This NMA confirms that adopting total neoadjuvant therapy improves outcome compared to other preoperative strategies, including FP-based CTRT.