Biliary Tract Cancer Rates Vary by Country; Prevention Efforts Needed

Biliary tract cancer (BTC), a category that includes gall bladder cancer and more deadly forms of cholangiocarcinoma, is rising worldwide, a trend likely related to increased incidence of diabetes and obesity, according to new results gleaned from international databases and published in the journal Gastro Hep Advances.

Authors wrote that their analysis was the first to combine incidence and mortality of overall BTC, and its anatomic subtypes, into a single study.

Rates of BTC varied by country, with more cases seen in Asia and South America than in Europe or North America. In most countries, gall bladder cancer (GBC) accounted for the highest number of cases, but intrahepatic cholangiocarcinoma (ICC) proved more deadly. Other types included in the study were ampulla of Vater cancer (AVC) and extrahepatic cholangiocarcinoma (ECC).

Study authors said the increased incidence and mortality trends showed a need for better prevention and treatment of all types of BTC. “These findings may provide important public health guidance for intervention strategies and the development of therapeutics related to geographic groups with differing BTC rates,” they wrote.

The authors derived their data from the International Agency for Research on Cancer, Cancer Incidence in Five Continents, Volume XI (2008–2012), which included data on 22 countries; and the World Health Organization Mortality Database (2006–2016) which had data from 38 countries. Deaths from BTC rose during the years studied.

BTC incidence, expressed as cases per 100,000 person-years, was highest in Chile, with 14.35 cases, and lowest in Vietnam, at 1.25 cases. Mortality rates were highest for South Korea (11.64) and lowest for Moldova (1.65). Patients who were at least 75 years had morality rates that were 5-10 times higher than overall rates. More women developed and died from GBC, but more men developed and died from ICC, ECC, and AVC.

Geographic differences. Incidence rates were highest in the Asia-Pacific region (1.12–9.00) and in South America (2.73–12.42), compared with those for Europe (2.00–3.59) and North America (2.33–2.35). Within the United States, BTC incidence was 1.3 times higher for Asian Americans than the general population.

The deadliest subtype, ICC, had an incidence rate of 2.18 in South Korea, with the lowest rate in Vietnam (0.16). Higher rates in Asian-Pacific countries have been attributed to infection with the parasite liver flukes in several Asian countries. The authors found that while BTC rates remained higher in this region, the authors also found signs that some prevention efforts are working.

“Although we report the BTC incidence rate in Thailand as one of the highest among the countries included in this analysis, a recent study showed a decrease in cholangiocarcinoma incidence between 2002 and 2013 in a northern Thailand province, which coincided with preventative measures concerning liver flukes,” they wrote.

Comorbidities. The authors wrote that rising rates of diabetes, obesity, and non-alcoholic fatty liver disease may be contributing to the rising incidence of BTC. “A meta-analysis of observational studies found that body mass index status of overweight and obese was associated with increased risk of ECC and GBC,while a different study suggested that diabetes and obesity increased the risk of ICC.”

Lifestyle factors may play a role as well. Higher alcohol consumption was linked to ICC, and authors found a dose-repsonse trend. Study results also aligned with recent findings that the different varies of BTC and cholangiocarcinoma may act as very different cancers, with each one affected by specific risk factors. Thus, the authors wrote, the results show the need for “separating epidemiologic data by subtype in order to better understand disease etiology.”

The authors acknowledged that their results may be affected by the challenges in getting an accurate BTC diagnosis in some countries; for example, they note that BTC is often classified as hepatocellular carcinoma. Inaccurate or delayed diagnoses can lead to poor treatment and outcomes, because initial treatment with surgery may not be possible once the cancer progresses.

As treatments improve, accuracy diagnosis becomes more important, the authors wrote.

“Improved diagnosis of BTC is also relevant to advances in targeted treatment as BTC subtypes may respond differently to treatments as suggested by studies showing that some subtypes have targetable molecular alterations,” they said. “This is especially relevant, since targeted therapies have recently shown remarkable results in biomarker-selected patient populations, potential which could be exploited in combination with the more recent proposed schemas of immunotherapy.”

The study was funded by AstraZeneca.

Reference

Baria K, De Toni EN, Yu B, Jiang Z, Kabadi SM, Malvezzi M, World-wide incidence and mortality of biliary tract cancer. Gastro Hep Advances. Published April 12, 2022.doi: https://doi.org/10.1016/j.gastha.2022.04.007.