Changing pattern of epidemiology in intrahepatic cholangiocarcinoma
Authors: Basile Njei
Journal: Hepatology (2013)

Intrahepatic cholangiocarcinoma (ICC) accounts for up to 15% of primary liver cancer cases and is the second most common primary hepatic malignancy after hepatocellular carcinoma.1, 2 The emerging importance of ICC has been recognized by the American Joint Committee on Cancer (AJCC) and a separate staging system for ICC has been included in the most recent 7th edition of the AJCC staging manual.2 Globally, the age-adjusted incidence of ICC has increased from 0.32 per 100,000 to 0.85 per 100,000 over a 30-year period.2, 3 Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, Patel4 reported a 9.1% increase in ICC incidence in the United States from 1973 to 1997. More recently, several studies have indicated rising trends in the incidence of this malignancy.5-7 Despite the increased awareness of ICC, long-term survival is poor because of late presentation of disease and limited therapies.5, 6 We hypothesize that increased awareness of this disease and advances in imaging/surgical technology may have improved survival of patients with ICC. If these survival benefits are large enough, they should be detectable in a temporal trend analysis of ICC incidence and mortality. We therefore sought to examine trends in ICC incidence and incidence-based (IB) mortality in the U.S. using the National Cancer Institute (NCI) SEER program data from 1973 to 2010. The NCI Joinpoint Regression Analysis program, v. 3.5.3,7 was used to examine trends in overall ICC incidence and IB mortality. The Joinpoint program selects the best-fitting piecewise continuous log-linear model, where the segments are connected at "joinpoints," and statistical tests are performed to determine the minimum number of joinpoints necessary to fit the data. All Joinpoint program settings remained in the default mode; the incidence and IB mortality data were modeled in a segmented loglinear form. For each linear segment, annual percentage changes (APC) in age-adjusted incidence and IB mortality were calculated and 95% confidence intervals (CIs) were reported. During the study period, 8,805 patients (50.9% males) met our inclusion criteria. In 1973 the ICC incidence was 0.07 cases per 100,000, whereas in 2010 the ICC incidence was 0.73 cases per 100,000 (Fig. 1A). From 1973 to 1993 the APC was 5.0% (95% CI: 3.6-6.5; P < 0.05), whereas from 1993 to 2010 the change was 0.8% per year (95% CI: −0.3-1.9; P > 0.05). Interestingly, although ICC mortality also increased from 1973 to 1996 (APC of 4.8% per year [95% CI: 3.9-5.7]), from 1996 to 2010 there was a significant decrease trend (APC of −2.5% per year [95% CI: −1.3 to −3.7] Fig. 1B). The diagnosis of ICC at the localized stage and utilization of surgery significantly increased over the study period (12% to 32%, P < 0.05 and 9% to 22%, P < 0.05, respectively). Our results show that the incidence of ICC in the U.S. has increased from 1973 to 2010, with a slowing of the rate of increase occurring around 1993. ICC IB mortality initially followed a similar pattern of a continued rise, but since 1996 the mortality rate has been decreasing annually. Over the study period, there was a progressive increase in detection at early stages, when it is potentially curable. Although ICC often carries a poor prognosis, detection at an early stage may offer the promise of improved survival. Basile Njei, M.D., MPH Department of Medicine University of Connecticut Farmington, CT