Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017

Abstract

Background: Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015.

Patients and methods: Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3: C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA.

Results: Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%).

Conclusions: CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification.

Keywords: SEER program; cholangiocarcinoma; incidence; mortality; prevalence; unknown primary tumor.

Figure 1.

Patient disposition. ^aPatients diagnosed with iCCA (ICD-O-3 code: C221) or eCCA (ICD-O-3 codes: C240, C241,249). ^bCancer of unknown primary (ICD-O-3 code C809) and adenocarcinoma histology codes 8140/2 (adenocarcinoma in situ), 8140/3 (adenocarcinoma not otherwise specified), 8141/3 (scirrhous adenocarcinoma), 8143/3 (superficial spreading adenocarcinoma), and 8147/3 (basal cell adenocarcinoma). Abbreviations: CCA, cholangiocarcinoma; CUP, cancer of unknown primary; eCCA, extrahepatic cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma; ICD-O-3, International Classification of Diseases for Oncology.

Figure 2.

Age-adjusted incidence of CCA, iCCA, eCCA (A), CUP (B); incidence of CCA by age (C), sex (D), and race (E); annual mortality rates for CCA, iCCA, eCCA, and CUP (F) from 2001 to 2017. Incidence was determined per 100 000 p-y and age-adjusted to the US standard population of 2000. Also shown in panel B is the incremental difference between age-adjusted iCCA and CUP incidences from 2001 to 2017. Note that interpretation of trends in CCA incidence in the American Indian/Alaska Native cohort is limited by the correspondingly small sample size (n = 327). Abbreviations: CCA, cholangiocarcinoma; CUP, cancer of unknown primary; eCCA, extrahepatic cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma; p-y, person-year.

Figure 3.

Overall survival: (A) CCA, CUP; (B) iCCA, eCCA, CUP. Abbreviations: CCA, cholangiocarcinoma; CI, confidence interval; CUP, cancer of unknown primary; eCCA, extrahepatic cholangiocarcinoma; HR, hazard ratio; iCCA, intrahepatic cholangiocarcinoma.