Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies

Background: The role for adjuvant radiotherapy (ART) after curative resection in extrahepatic cholangiocarcinoma remains unclear. Due to the lack of randomized trials, available data comes from single center experiences or data-based population studies with inconclusive results.

Objective: To assess the impact of radiotherapy (with or without concurrent chemotherapy) on toxicity and survival of radically resected patients with extrahepatic bile duct cancer (extrahepatic cholangiocarcinoma, gallbladder cancer and pure ampullary cancer).

Data sources and study selection: Eligible studies with data on survival, recurrence and toxicity were retrieved from the MEDLINE, ISI web of science, EMBASE and Cochrane databases from January 1995 to December 2008, to ensure that all ART treatments were performed with conventional 3D techniques. In the absence of randomized controlled-studies, all observational cohort studies (longitudinal and historical) were initially considered. Ten retrospective cohort studies (where the use of concurrent CT was reported only in 2), met all inclusion criteria and were enrolled for final meta-analysis. Hazard ratio (HR) had to be extracted from survival curves using the Tierney et al. methods. MIX 1.7 statistical software was used for meta-analysis.

Results: All studies on ART used conventional 3D-techniques. Patients in the ART cohorts were more likely to have involved surgical margins and positive lymph nodes. For extrahepatic cholangiocarcinoma location, ART significantly improved overall survival (HR 0.62; 95% CI 0.48 to 0.78, p<0.001). Meta-analysis was not feasible for gallbladder cancer and ampullary cancer locations. Late radiation-induced toxicity was low (2-9% late obstruction or GI bleeding).

Conclusion: In the absence of randomized controlled studies, we found in the present systematic review and meta-analysis of observational studies that, patients with extrahepatic cholangiocarcinoma treated with adjuvant RT have a significant lower risk of dying compared to patients treated with surgery alone.