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Trends in Survival After Surgery for Cholangiocarcinoma: a 30-Year Population-Based Seer Database Analysis
Hari Nathan*, Timothy M. Pawlik, Richard D. Schulick
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD

Background: The prognosis of patients (pts) with cholangiocarcinoma (CCA) has traditionally been poor even after surgical resection. Over the last decade, several single-institution surgical series have reported modest improvements in long-term survival. Outcomes after surgical resection of CCA have not been investigated in a large population-based study.
Objective: To analyze population-level trends in survival after surgery for CCA.
Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify pts with CCA who underwent cancer-directed surgery during 1973-2002. Pts with CCA were stratified by tumor location: extrahepatic (including perihilar) (ECC) or intrahepatic (ICC). Relative survival (RS) was analyzed by the Kaplan-Meier method. Factors associated with survival were examined using Cox proportional hazards models.
Results: Between 1973 and 2002, 2,698 pts underwent surgery for CCA (Table). Survival after surgical resection of ECC improved over time. Pts diagnosed in 1973-1982 had a 5-year RS of 14.4%, significantly worse than those in 1983-1992 (19.1%, P<0.01) or 1993-2002 (24.5%, P<0.001). Multivariate analysis revealed a cumulative 53.7% decrease in the risk of mortality from 1973 to 2002. In contrast to ECC, pts with ICC did not have an improvement in survival until the last decade studied (5-year RS 16.5% in 1973-1992 vs. 22.9% in 1993-2002, P<0.01). In multivariate analysis, this improvement in the last decade compared with previous decades did not remain significant. Multivariate analysis did reveal, however, a more recent year-to-year improvement in ICC survival within the last decade. Specifically, there was a cumulative 34.4% decrease in the risk of mortality from 1992 to 2002.
Conclusions: Survival after surgery for ECC has dramatically improved over the past 30 years. Pts with ICC, however, have enjoyed a more modest improvement in survival largely confined to the last 10 years. Further studies are necessary to determine whether such trends are due to advances in hepatobiliary surgical technique, imaging technology, or more aggressive surgical approaches.
Summary Survival Statistics and Significant Results of Multivariate Analysis

Extrahepatic(n=2,107) Intrahepatic(n=591)
Median relative survival (months) 18 21
Five-year relative survival (%) 20.5 20.6
Variable Hazard Ratio P-Value Hazard Ratio P-Value
Age at diagnosis 1.03per year over 60 <0.001 1.18per year over 80 <0.001
Year of diagnosis 0.97per year after 1972 <0.001 0.96per year after 1992 <0.01
StageLocalizedRegionalDistant .Reference1.613.57 ..<0.001<0.001 .Reference1.733.06 ..<0.001<0.001
GradeWell differentiatedModerately differentiatedPoorly differentiatedUndifferentiated .Reference1.191.671.38 ..<0.05<0.001NS .Reference1.051.181.81 ..NSNSNS
Rural location 1.43 <0.001 0.75 NS

NS=Not Significant (α=0.05)

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