Combined hepatocellular-cholangiocarcinoma: a population level analysis of incidence and mortality trends

Abstract

Background The purpose of this study was to explore trends in incidence, incidence-based (IB) mortality, and survival for combined hepatocellular-cholangiocarcinoma (cHCC-CC) utilizing a population-based database to attract people’s attention to this disease. Methods The Surveillance, Epidemiology, and End Results (SEER) database was utilized to investigate the incidence and IB mortality for cHCC-CC from 2000 to 2014. Trends in age-adjusted incidence and IB mortality were characterized by the Joinpoint Regression program. The Kaplan-Meier method and log-rank test were utilized to implement survival analyses. Cox regression was utilized to estimate independent predictors of mortality. Results The incidence of cHCC-CC was 0.26 per 1,000,000 individuals in 2000 and 0.59 per 1,000,000 individuals in 2014, with an annual percent change (APC) (i.e., the extent of increase in incidence) of 3.84% (95% confidence interval [CI] 1.7–6.1; P < 0.05). The IB mortality also displayed a sustained increase (APC was 4.59%, 95% CI 1.9–7.4; P < 0.05). Compared to patients not undergoing surgery, patients undergoing surgical treatment experienced a significant increase in median survival (3 vs. 28 months; P < 0.001). However, the median survival decreased in patients with tumor size > 5 cm (20 vs. 9 months; P < 0.001). Based on univariate Cox regression analysis, African-American race, distant stage, regionalized stage, tumor size ≥ 5 cm, and no surgery were risk factors for death. Conclusions We identified an overall steady increase in the incidence of cHCC-CC, which indicates that primary prevention strategies for cHCC-CC have not improved much in recent years and that cHCC-CC needs to be taken seriously.

Global Trends in Incidence Rates of Primary Adult Liver Cancers: A Systematic Review and Meta-Analysis

“…One study reported an increase in the incidence of cHCC-CC among both males and females over recent decades until 2014 in the USA (71).…”

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

“…cHCC-ICC is staged by TNM in a clinical context (as opposed to SEER staging of epidemiological data) using the same staging algorithm as for ICC ( Table 3 ) ( 64 – 66 ). It is difficult to get accurate measures of patient survival without treatment (i.e., the true prognosis) but two large epidemiological datasets from the United States provide some guidance ( 12 , 67 ). Median overall survival (mOS) of patients stratified by the SEER stage for distant, regionalized, and localized cHCC-HCC was 4 months (95% CI, 3–6), 7 months (95% CI, 5–11), and 20 months (95% CI 16–28), respectively ( p < 0.001), with the difference between regionalised and localized explained by suitability for resection ( 12 ).…”

“…It is difficult to get accurate measures of patient survival without treatment (i.e., the true prognosis) but two large epidemiological datasets from the United States provide some guidance ( 12 , 67 ). Median overall survival (mOS) of patients stratified by the SEER stage for distant, regionalized, and localized cHCC-HCC was 4 months (95% CI, 3–6), 7 months (95% CI, 5–11), and 20 months (95% CI 16–28), respectively ( p < 0.001), with the difference between regionalised and localized explained by suitability for resection ( 12 ). A similar pattern is seen using TNM staging data from the National Cancer Data Base (NCDB) where mOS was 28.6 m for patients with Stage I disease, 24.2 m for stage II, 7.5 m for stage III and 3.1 m for stage IV ( 67 ).…”

“…cHCC-ICC is likely to comprise between 0.4 and 4.7% of all PLCs, incidence ratio for male:female patients is 1.8–2.1:1 and median age at diagnosis is 62–65 years-old ( 2 , 6 – 12 ). Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute reveals that patients tend to present with distant, metastatic disease (130/380, 34.2%) rather than localized (98/380, 25.8%) or regional disease (97/380, 25.5%) according to their generic staging system ( vida infra ) ( 11 , 12 ). The risk factors remain unclear and retrospective case-control studies report conflicting associations; some Asian studies suggest similarities between the risk factors for hepatocellular carcinoma (HCC) and cHCC-ICC such as chronic liver disease caused by infection with hepatotropic viruses such as hepatitis B (HBV) or hepatitis C (HBC) and alcohol.…”

Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma

“…The classi cation of cHCC-CCA has been modi ed since Allen and Lisa rst described it in 1949, and the World Health Organization (WHO) recently updated its taxonomy [1,3,4]. Because of the rarity of cHCC-CCA, its etiology, clinicopathological features, and prognosis in comparison with other primary liver carcinoma remain unknown [5][6][7][8][9][10][11]. Its recurrence pattern and sites and the optimal treatment for recurrence in particular need to be elucidated [12].…”