Comparison of different chemoradiotherapy regimens for the preoperative treatment in patients with locally advanced rectal cancer: a network meta-analysis

Background: The efficacy of different neoadjuvant chemoradiotherapy regimens on locally advanced rectal cancer (LARC) remains confusing. We evaluated them together via a network meta-analysis in terms of survival benefits to find the optimal treatment. Methods: We searched , EMBASE, Cochrane Central Register of Controlled Trials and the ClinicalTrials website according to the selection criteria for eligible publications before Oct 25, 2019. Pathological complete response rate (pCR), disease-free survival (DFS), and overall survival (OS) were analyzed based on Bayesian methods in the meta-analysis. Results: Twenty-five articles containing 7,142 participants and 12 preoperative regimens were analyzed. In terms of pCR, radiation therapy plus 5-fluorouracil (RT+5-Fu), RT plus capecitabine (RT+CAPE), RT plus 5-fluorouracil and oxaliplatin (RT+FOLFOX), RT plus capecitabine and oxaliplatin (RT+XELOX), and RT plus S-1 and irinotecan (RT+IS) were better than RT alone [odds ratio (OR) =2.66, 95% credible interval [CrI], 1.38-5.01; OR =3.11, 95% CrI: 1.33-6.98; OR =4.03, 95% CrI: 1.77-9.47; OR =4.22, 95% CrI: 1.60-10.87; OR =4.55, 95% CrI: 1.11-18.88, respectively] and RT+FOLFOX and RT+XELOX were superior to FOLFOX (OR =4.58, 95% CrI: 1.57-14.19; OR =4.81, 95% CrI: 1.20-18.73), too. Benefits could be seen on comparing RT+CAPE, RT+FOLFOX, and RT+XELOX with RT (OR =0.84, 95% CrI: 0.73-0.97; OR =0.88, 95% CrI: 0.80-0.97; OR =0.79, 95% CrI: 0.66-0.95, respectively) in DFS. RT+XELOX seemed to have better effects on OS compared than RT+5-Fu and RT+CAPF, (OR =0.78, 95% CrI: 0.61-1.(X); OR =0.86, 95% CrI: 0.74-1.00, respectively). Moreover, according to surface under the cumulative ranking curve analysis, RT+XELOX had the best outcomes in terms of pCR (79.18%) and OS (83.49%) and RT plus capecitabine, irinotecan, and cetuximab (RT+XELIRI+CET) ranked first with respect to DFS (87.86%). Conclusions: RT+XELOX is likely to be the best treatment with a comprehensive curative effect and the standard treatment of 5-fluorouracil-based chemoradiotherapy has some advantages, as well. More relevant evidence is needed for clinicians' guidance.