Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis

Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies. We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48–0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47–0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17–0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27–0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30–3.19, P=0.98). Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26–0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29–4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14–2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13–0.64, P=0.002). A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.