Efficacy And Safety Of Three Local Palliative Therapies For Unresectable Malignant Biliary Obstruction:A Bayesian Network Meta-analysis

Background and Objective: Biliary stent alone and radiofrequency ablation（RFA）or photodynamic therapy（PDT）combined with biliary stent are common local palliative therapies for unresectable malignant biliary obstruction（MBO）,but advantages and disadvantages of these three treatment modalities are uncertain.Thus,we performed a Bayesian network meta-analysis to compare efficacy and safety of the three modalities comprehensively in unresectable MBO.Methods: Embase,Cochrane Library,Pub Med,and Web of Science were systematically searched up to Jan 30,2022,for eligible studies that compared two or all of the above modalities in unresectable MBO.The revised Cochrane Risk of Bias Assessment Tool and ROBINS-I were used to assess the methodological quality of the included studies.The quality of evidence for the results were evaluated by GRADE.The main outcomes included overall survival,mean survival time,mean stent patency time,stent patency rate,alleviation of total bilirubin,and common postoperative complications.This Bayesian meta-analysis was performed based on random effects model using the "gemtc" and "rjags" packages of R software（version 4.0.2）and Open BUGS software.Results: Thirty-three studies with 2974 patients were included in this study.The PDT+Stent and RFA+Stent groups had better overall survival and longer mean survival time than Stent alone group（P<0.05）.Moreover,RFA+Stent group demonstrated better mean duration of stent patency [MD=2.0,95%CI（1.1,2.8）] and stent patency rate at six months [OR=3.1,95%CI（1.6,6.5）] than Stent alone group.The three modalities had similar incidence of postoperative mild bleeding,cholangitis,and pancreatitis（P<0.05）.According to network ranking,PDT+Stent was most likely to provide better survival,RFA+Stent was most likely to maintain stent patency.In terms of postoperative complications,RFA+Stent had the highest incidence of mild bleeding,while PDT+Stent had the highest incidence of cholangitis and pancreatitis.According to the latest GRADE evidence evaluation criteria,high-certainty evidence showed that PDT+stent and RFA+ tent were significantly better than the Stent alone in improving overall survival;In terms of mean survival time: high-certainty evidence showed that PDT+stent and RFA+stent were significantly better than the Stent alone,and it was determined that PDT+ stents were significantly more effective than RFA+ stents（lowcertainty evidence）;In terms of mean time to stent patency and 6-month stent patency rate,high-certainty evidence showed that RFA+stent was significantly better than the Stent alone,whereas there was no difference between PDT+stent and the Stent alone（low-certainty）,and RFA+stent was not significantly better than PDT+stent（lowcertainty）;There were no significant differences between the three local palliative therapies in the remaining outcomes: 3-month stent patency rate and incidence of cholangitis（high-certainty evidence）,mild bleeding,and incidence of pancreatitis（lowcertainty evidence）,and the degree of total bilirubin remission（low-certainty evidence）.Conclusion: RFA or PDT plus biliary stenting therapy is effective and safe local palliative therapy for unresectable MBO.Although the results of the current studies available cannot determine which modality is absolutely best from RFA and PDT,we can provide patients with the most appropriate individualized treatment based on the advantages of each measure in this study and in conjunction with their disease status and treatment wishes.