Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-analysis

Abstract

IMPORTANCE: Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. OBJECTIVE: To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. DATA SOURCES: The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. STUDY SELECTION: Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. DATA EXTRACTION AND SYNTHESIS: Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. RESULTS: Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). CONCLUSIONS AND RELEVANCE: The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.