Intrahepatic cholangiocarcinoma: the equity gap in one of the most lethal cancers

Pancreatic cancer is considered the most recalcitrant and deadliest malignancy in the United States. With a 5-year survival of about 13% across all stages, and a median survival of less than 12 months in the metastatic setting, this reputation is well earned (1). In the October 2025 issue of the Journal of Gastrointestinal Oncology, Dharia and colleagues report similarly sobering survival numbers for intrahepatic cholangiocarcinoma (ICC) (2). Although not specifically reviewed by the authors, the numbers are similar for other biliary tract cancers (BTCs), including extrahepatic cholangiocarcinoma and gallbladder cancer (3).

Using the Surveillance, Epidemiology, and End Results (SEER) 22 database, the authors highlighted ethnic and socioeconomic disparities in survival outcomes for ICC among patients aged 20 to 64 years, a cohort ineligible for Medicare. They report a median survival of only 10 months across all stages, and 6 months in advanced ICC. This is particularly dispiriting as the analysis involved a younger cohort (median age 57 years). Our group similarly reported a median survival of only 4.5 months among a more representative cohort of patients (median age 70 years) with advanced BTC (4).

As with other recalcitrant tumors, the poor outcomes in BTC can be attributed broadly to a combination of two factors: aggressive disease biology that may potentiate presentation at a more advanced stage, and a failure of drug development. The authors highlight ’stage at presentation’ as a particularly important prognostic factor in ICC. However, the relative contributions of aggressive biology and inadequate social and economic infrastructure to late presentation are difficult to untangle.

Histologically, ICC is classified into small duct and large duct subtypes. Large duct ICC has been associated with a more aggressive phenotype with worse prognosis (5). Conversely, molecular features associated with better prognosis, such as fibroblast growth factor receptor 2 (FGFR2) fusions and more controversially, isocitrate dehydrogenase 1 (IDH1) mutations, are more abundant in the small duct subtype (6). While there is a scarcity of data on the prevalence of these histologic subtypes across racial groups, the available data suggests that IDH1 mutations are more common in Whites and Hispanics (than Blacks), and FGFR2 fusions are more common in Blacks (7). Despite these, Blacks present with more advanced disease at diagnosis and overall have worse outcomes, and Hispanics (and Native Americans) continue to show worse outcomes than Whites. Prospective data comparing survival outcomes across racial and ethnic groups with molecularly matched (and appropriately treated) ICC may provide more insight into the impact of tumor biology on ICC outcomes, independent of other structural deficiencies in society.

In the absence of this information, we are left to deal with the reality of a devastating disease that disproportionately affects minority groups and how to respond to this. An effective screening program is an important mitigator for late-stage presentation (8,9). This has led to improved overall survival in some malignancies (10,11). Unfortunately, except for patients with primary sclerosing cholangitis, there are no screening programs for BTC. Nevertheless, diabetes mellitus and metabolic dysfunction-associated fatty liver disease (MAFLD) are important risk factors for ICC, and there is a significant overlap between the ethnic groups that are affected by these disorders and those affected by ICC. Aggressive campaigns to prevent and treat these disorders in the affected population may lead to significant improvement in the burden of ICC. In this context, more widespread adoption of glucagon-like peptide-1 (GLP-1) receptor agonists, and the expected improvement in the prevalence of metabolic dysfunction related disease may have a positive effect on the epidemiology of ICC in the next decade.

Beyond racial or ethnocultural identity, structural barriers such as income, health literacy, and geographic location also affect access to subspecialty multidisciplinary care. Such care is often only available in academic centers and large healthcare facilities, which are also concentrated in larger cities (12). A particularly interesting finding from the study by Dharia and colleagues was that ‘stage at presentation varied significantly by ethnicity but not by income’ (2). There was no difference in the proportion of those who presented with distant disease among the lowest and highest income groups. Given their finding that the income group >$100,000 had the highest survival rates, it is reasonable to surmise that the relatively higher income confers advantages after diagnosis, including access to specialized multidisciplinary and supportive care (13). Again, it is impossible to ignore the obvious sociodemographic implications here; the minority groups that bear the burden of ICC are also more likely to fall into the lower-income groups.

Recent advances in the development of immune checkpoint inhibitors for the management of advanced and metastatic ICC have led to modest improvements in survival outcomes (14,15). Second line treatments targeting FGFR2 fusions and (to a lesser extent IDH1 mutations) have also delivered impressive responses (16,17). Drug development is therefore accelerating in ICC. The challenge over the next few years is to ensure equitable delivery of the gains that will accrue from these developments. In addition to aggressive management of recognized risk factors like diabetes and MAFLD, designing pragmatic clinical trials that are available within the communities, and that emphasize enrolling minority populations that bear the burden of ICC, will be critical to achieving improvements in outcomes. The findings of this SEER analysis highlight the importance of multilevel, multidisciplinary collaboration among primary care physicians, oncologists, researchers, and policymakers to reduce the burden of ICC across communities in the United States.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0185/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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