Incidence and mortality for biliary tract cancer (BTC) are both on the rise worldwide, according to a new analysis of data from the International Agency for Research on Cancer and the World Health Organization.
This diverse group of hepatic and perihepatic cancers include gallbladder cancer (GBC), intrahepatic and extrahepatic cholangiocarcinoma (ICC and ECC), and ampulla of Vater cancer. Although BTC is considered rare, incidence of its subtypes can vary significantly by geographic region. Because BTC is typically asymptomatic in its early stage, diagnosis is often made after tumors have spread, when there are few therapeutic options available. In the United States and Europe, 5-year survival is less than 20%.
Although previous studies have examined worldwide BTC incidence, few looked at multiple global regions or at all subtypes. Instead, subtypes may be grouped together and reported as composites, or BTC is lumped together with primary liver cancer. “To our knowledge, this is the first report combining data on worldwide incidence and mortality of all BTC subtypes per the International Classification of Diseases, Tenth Revision,” the authors wrote in the study, published online in Gastro Hep Advances.
The researchers pointed out that classification coding systems have improved at defining BTC subtypes, so that studies using older coding subtypes could cause misinterpretation of incidence rates.
BTC subtypes also have unique sets of risk factors and different prognoses and treatment outcomes. “Thus, there is a need to define accurate epidemiologic trends that will allow specific risk factors to be identified, guiding experts in implementing policies to improve diagnosis and survival,” the authors wrote.
The study included data from 22 countries. BTC incidence ranged from 1.12 cases per 100,000 person-years in Vietnam to 12.42 in Chile. As expected, incidence rates were higher in the Asia-Pacific region (1.12-9.00) and South America (2.73-12.42), compared with Europe (2.00-3.59) and North America (2.33-2.35). Within the United States, Asian Americans had a higher BTC incidence than the general population (2.99 vs. 2.33).
In most countries, new cases were dominated by GBC, while ICC was the most common cause of death.
In each country, older patients were 5-10 times more likely to die than BTC patients generally. The sixth and seventh decades of life are the most common time of diagnosis, and treatment options may be limited in older patients.
Risk factors for BTC may include common comorbidities like obesity, nonalcoholic fatty liver disease, and diabetes. Each is increasing individually, which may in turn contribute to rising BTC incidence. Observational analyses suggest that obesity may contribute to risk of ECC and gallbladder cancer, while diabetes and obesity may raise the risk of ICC. Smoking is associated with increased risk of all BTC subtypes except GBC, and alcohol consumption is associated with ICC.
“This study highlights how each subtype may be vulnerable to specific risk factors and emphasizes the value of separating epidemiologic data by subtype in order to better understand disease etiology,” the researchers wrote.
Risk factors associated with incidence and mortality from BTC aren’t limited to clinical characteristics. Genetic susceptibility may also play a role in incidence and mortality of different subtypes. There is also a relationship between gallstones and BTC risk. In Chile, about 50% of women have gallstones versus 17% of women in the United States. The cancer incidence is 27 per 100,000 person-years in Chile and 2 per 100,000 person-years in the United States. BTC is also the leading cause of cancer death among women in Chile.
The authors also highlighted the high rates of gallbladder cancer in India, despite a low prevalence of gallstones. Incidences can vary with geography along the flow of the Ganges River, which might reflect varying risks from contamination caused by agricultural runoff or industrial or human waste.
Worldwide BTC incidence and mortality was generally higher among women than men, with the exception of ampulla of Vater cancer, which was more common in men.
The study is limited by quality of data, which varied significantly between countries. Mortality data was missing from some countries know to have high BTC incidence. The databases had little survival data, which could have provided insights into treatment efficacy.
The study was funded by AstraZeneca. The authors have extensive financial relationships with pharmaceutical companies.