Adjuvant therapy in the treatment of biliary tract cancer (BTC): A systematic review and meta-analysis.

Abstract

4050 Background: The benefit of adjuvant therapy (AT) for BTC is unclear with conflicting results from non-randomized studies. We report a systematic review and meta-analysis to determine the impact of AT on survival, and hence identify treatment strategies and disease subgroups that merit further study in prospective trials. Methods: A systematic review of studies and abstracts published from 1960 to November 2010 was conducted. Eligible studies evaluated outcomes with chemotherapy (CT), radiotherapy (RT) or both (CRT) in resected BTC. Only studies where the comparator group was curative intent surgery alone were included. BTC included tumors of the gallbladder and intrahepatic, perihilar and distal bile ducts. Ampullary tumors were excluded. The endpoint of interest was the odds of death at 5 years (OR). Data on lymph node (N+) or resection margin positivity (R1) were collected. Data were pooled using random effect modeling. Results: 20 studies involving 6,712 patients were analyzed (surgery alone: 4,915; AT: 1,797). These included 1 randomized trial of CT, 2 registry analyses and 17 institutional series, largely RT or CRT. In the overall population, pooled data showed a trend to improved survival with any AT compared to surgery alone, OR 0.74 (95% CI 0.55 - 1.01; p=0.06). There was no difference between individual disease sites (gallbladder OR 0.81, bile ducts OR 0.71). The association was significant when 2 studies of largest weight, both registry analyses, were excluded. On sensitivity analysis, the effect was dependent on treatment modality, those receiving CT or CRT deriving greater benefit than RT alone (OR 0.39, p <0.001, OR 0.61, p=0.049 and OR 0.63, p=0.14 respectively). Eight studies reporting nodal (n=230) or margin status (n=216) were analyzed. Pooled data confirmed a significant benefit for AT in N+ disease, OR 0.49 (95% CI 0.30-0.80). Similarly, a benefit for AT was seen in R1 disease, OR 0.36 (95% CI 0.19-0.68). Conclusions: With the caveats of limited data, this review supports AT for BTC. International randomized trials are needed to provide better rationale for this commonly used strategy in BTC subgroups. Based on our data, such trials could involve CRT vs. CT alone in patients with N+ or R1 disease.