Ethnic and socioeconomic disparities in survival outcomes among patients under 65 years with intrahepatic cholangiocarcinoma: a SEER analysis
Highlight box
Key findings
• In this population-based study of 8,585 patients aged 20 to 64 years with intrahepatic cholangiocarcinoma (iCCA), significant disparities in overall survival were observed by race, income, and sex. These differences remained statistically significant even after adjusting for stage at diagnosis.
What is known and what is new?
• Prior studies have documented disparities in iCCA outcomes, but few have focused specifically on patients under 65 years of age, an age group that may lack Medicare coverage and face unique barriers to care.
• This study is the first to use Surveillance, Epidemiology, and End Results data to analyze survival disparities in patients aged 20 to 64 years with iCCA, identifying markedly worse outcomes among non-Hispanic Black, American Indian/Alaska Native, and lower-income groups despite similar stage distribution.
What is the implication, and what should change now?
• The findings highlight the need for targeted health policy and care delivery interventions aimed at improving access to timely diagnosis and treatment for patients under 65 years of age. Expanding equitable access to oncology services, particularly outside of Medicare coverage, may help mitigate survival disparities in this high-risk population.
Introduction
Intrahepatic cholangiocarcinoma (iCCA), the second most common primary liver tumor, is an aggressive malignancy with poor survival (1,2). Based on prior epidemiologic studies, the median age at diagnosis is approximately 65 years (1). In recent years, the global incidence of iCCA has steadily increased (1), with pronounced disparities based on race, ethnicity, geography, and socioeconomic status (3,4). Patients under 65 years of age, may experience delays in diagnosis and treatment, partly due to lack of Medicare eligibility and limited access to specialized care (5). Yet this population remains underrepresented in outcome studies, particularly those focused on disparities (4).
In this population-based study using the Surveillance, Epidemiology, and End Results (SEER) data, we evaluated overall survival (OS) in patients aged 20–64 years with iCCA, focusing on differences by race, income, age group, and sex. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-411/rc).
Methods
This retrospective cohort study used data from the SEER 22 registry, a population-based cancer database encompassing multiple U.S. regions. As SEER data are de-identified, institutional review board approval was not required. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Patients aged 20 to 64 years with a diagnosis of histologically confirmed iCCA (ICD-O-3 code 8160/3 and primary site code C22.1) between 2004 and 2021 were included in the study. Patients with missing survival time, unknown race, income, or stage, or survival of less than one month were excluded. The study population was grouped into categories based on age (20–34, 35–44, 45–54, and 55–64 years), race/ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, non-Hispanic American Indian/Alaska Native, and Hispanic), income (<$50,000, $50,000–$74,999, $75,000–$99,999), and stage (localized, regional, and distant).
The primary endpoint was median overall survival (mOS), defined as time from diagnosis to death from any cause or last follow-up. Patients alive at last contact were censored. We also assessed 5-year OS. Variables of interest included age, sex, race/ethnicity, median household income, and cancer stage.
Statistical analysis
Descriptive statistics were used to summarize baseline characteristics. Kaplan-Meier (KM) analysis estimated median and 5-year OS, with comparisons by log-rank test. Cox proportional hazards regression was used for univariate and multivariate analysis to determine associations between covariates and OS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Differences in stage distribution by race and income were assessed with Pearson χ2 test. Analyses were conducted using R version 4.3.0 (R Foundation for Statistical Computing).
Results
Patient population
A total of 8,585 patients diagnosed with iCCA between 2004 and 2021 were included in the study. The study population was 47% female, with a median age of 57 years (range, 20–64 years) and a median household income of $77,500 [interquartile range (IQR), $62,500–$92,500]. Non-Hispanic White was the most common racial group, and 49% of patients presented with distant-stage disease. The median follow-up duration was 68 months (95% Cl: 65–72). At the time of analysis, 6,806 patients (79.3%) had died. The mOS for the overall cohort was 10 months (95% Cl: 10–11).
Survival by demographic and socioeconomic factors
In our study, we observed that ethnicity, income status and age at diagnosis impacted survival outcomes.
Ethnicity
Non-Hispanic Black (NHB) (mOS: 8 months; 95% CI: 7–10, 5-year OS: 12.9%) and Non-Hispanic American Indian/Alaska Native patients (NHAIAN) (mOS: 8 months; 95% CI: 5–15; 5-year OS: 10.2%) had the lowest survival rates, followed by Hispanic patients (mOS: 9 months; 95% CI: 8–10; 5-year OS: 14.5%). In contrast, NHW (mOS: 11 months; 95% CI: 11–12; 5-year OS: 19.2%) and Non-Hispanic Asian/Pacific Islander (NHAPI) patients (mOS: 12 months; 95% CI: 11–14; 5-year OS: 19.5%) exhibited significantly improved survival outcomes (P<0.001). KM curves showing OS stratified by race are presented in Figure 1.
Income
Lower-income status was associated with poorer survival outcomes. Patients in the lowest income category (<$50,000) had a mOS of 8 months (95% CI: 7–10) and a 5-year OS of 10.6%, whereas those in the highest income category (≥$100,000) had a mOS of 13 months (95% CI: 12–14) and a 5-year OS of 14.6% (P<0.001). KM curves showing OS stratified by income are presented in Figure 2.
Age and sex
Younger patients (20–34 years) demonstrated longer survival (mOS: 12 months; 95% CI: 11–16; 5-year OS: 12.9%), compared with older patients aged 55–64 years (mOS: 10 months; 95% CI: 9–10; 5-year OS: 11.9%) (P<0.001). Female patients had improved survival (mOS: 12 months; 95% CI: 12–13; 5-year OS: 14.5%) compared to males (mOS: 9 months; 95% CI: 8–10; 5-year OS: 10.8%) (P<0.001). Kaplan-Meier curves showing OS stratified by age and sex are presented in Figures 3,4, respectively. Survival outcomes of clinical subgroups are detailed in Table 1.
Table 1
| Variable | N [%] | Median OS (months) [95% CI] | 5-year OS (%) [95% CI] |
P value |
|---|---|---|---|---|
| Age group (years) | <0.001 | |||
| 20–34 | 250 [3] | 12 [11–16] | 12.9 [8.8–19.0] | |
| 35–44 | 733 [9] | 14 [12–16] | 15.9 [13.1–19.4] | |
| 45–54 | 2,181 [25] | 12 [11–12] | 12.8 [11.2–14.5] | |
| 55–64 | 5,421 [63] | 10 [9–10] | 11.9 [10.9–13.0] | |
| Sex | <0.001 | |||
| Female | 4,039 [47] | 12 [12–13] | 14.5 [13.3–15.8] | |
| Male | 4,546 [53] | 9 [8–10] | 10.8 [9.8–12.0] | |
| Race/ethnicity | <0.001 | |||
| Hispanic (all races) | 1,875 [22] | 9 [8–10] | 10.2 [8.6–12.1] | |
| Non-Hispanic American Indian/Alaska Native | 54 [1] | 8 [5–15] | 10.5 [4.2–26.4] | |
| Non-Hispanic Asian or Pacific Islander | 886 [10] | 12 [11–14] | 13.5 [11.0–16.5] | |
| Non-Hispanic Black | 889 [10] | 8 [7–10] | 12.9 [10.6–15.7] | |
| Non-Hispanic White | 4,881 [57] | 11 [11–12] | 13.1 [12.1–14.3] | |
| Income group | <0.001 | |||
| <$50,000 | 510 [6] | 8 [7–10] | 10.6 [8.0–14.1] | |
| $50,000–$74,999 | 3,754 [44] | 9 [9–10] | 11.7 [10.6–13.0] | |
| $75,000–$99,999 | 2,842 [33] | 12 [11–12] | 12.9 [11.4–14.5] | |
| ≥$100,000 | 1,479 [17] | 13 [12–14] | 14.6 [12.5–17.0] | |
| Stage at diagnosis | <0.001 | |||
| Localized | 2,069 [24] | 30 [27–32] | 32.9 [30.5–35.4] | |
| Regional | 2,304 [27] | 13 [12–14] | 11.4 [10.0–13.0] | |
| Distant | 4,212 [49] | 6 [6–7] | 3.1 [2.5–3.8] |
CI, confidence interval; OS, overall survival.
Survival by stage at diagnosis
Survival outcomes varied by disease stage at presentation in our study. Patients with localized disease had the longest survival (mOS: 30 months; 95% CI: 27–32; 5-year OS: 32.9%), followed by those with regional disease (mOS: 13 months; 95% CI: 12–15; 5-year OS: 11.4%). Patients with distant disease had the poorest outcomes (mOS: 6 months; 95% CI: 5–6; 5-year OS: 3.1%) (P<0.001). The details of survival outcome by demographic and clinical subgroups are provided in Table 1. KM curves showing OS stratified by stage are presented in Figure 5.
Multivariate analysis
On Cox proportional hazards analysis, younger age (<55 years), female sex, localized disease, and higher income (≥$75,000) were independently associated with improved survival. Compared with Hispanic patients, NHW (HR: 0.873; 95% CI: 0.821–0.928; P<0.001) and NHAPI patients (HR: 0.855; 95% CI: 0.780–0.937; P<0.001) exhibited significantly lower mortality risk. No significant survival differences were observed among NHB (HR: 0.981; P=0.676) or NHAIAN patients (HR: 1.183; P=0.268). Patients in the highest income bracket (≥$100,000) had a significantly reduced mortality risk (HR: 0.855; 95% CI: 0.798–0.916; P<0.001) compared with those earning $50,000–$74,999. The details are provided in Table 2.
Table 2
| Variable | Category | HR (95% CI) | P value |
|---|---|---|---|
| Stage | Localized | 0.295 (0.276–0.315) | <0.001 |
| Regional | 0.572 (0.540–0.605) | <0.001 | |
| Distant (ref) | – | – | |
| Sex | Male | 1.253 (1.194–1.314) | <0.001 |
| Female (ref) | – | – | |
| Age group (years) | 35–44 | 0.953 (0.809–1.122) | 0.56 |
| 45–54 | 1.126 (0.971–1.307) | 0.12 | |
| 55–64 | 1.281 (1.109–1.480) | <0.001 | |
| 20–34 (ref) | – | – | |
| Race/ethnicity | Non-Hispanic American Indian/Alaska Native | 1.183 (0.879–1.592) | 0.27 |
| Non-Hispanic Asian/Pacific Islander | 0.855 (0.780–0.937) | <0.001 | |
| Non-Hispanic Black | 0.981 (0.897–1.073) | 0.68 | |
| Non-Hispanic White | 0.873 (0.821–0.928) | <0.001 | |
| Hispanic (ref) | – | – | |
| Income group | <$50,000 | 1.067 (0.965–1.180) | 0.21 |
| $75,000–$99,999 | 0.914 (0.864–0.966) | 0.001 | |
| ≥$100,000 | 0.855 (0.798–0.916) | <0.001 | |
| $50,000–$74,999 (ref) | – | – |
CI, confidence interval; HR, hazard ratio; ref, reference group.
Stage at diagnosis and disparities in ethnicity and income
Interestingly, stage at presentation varied significantly by ethnicity but not by income. Hispanic patients had the highest proportion of distant disease at presentation (51.9%), whereas non-Hispanic White patients had the highest proportion of localized disease (24.9%, P=0.003 Among patients with annual income <$50,000, 47.3% presented with distant disease, compared with 48.8% in the ≥$100,000 income group (P=0.263).
Discussion
This large, population-based analysis of iCCA patients under 65 years revealed significant disparities in survival by race, socioeconomic status, and sex, independent of disease stage. Age- and sex-related differences were consistent with prior literature (2,3,6).
Previous studies have reported the poorest outcomes among Hispanic patients with iCCA (4); however, a different pattern was observed in this younger cohort. Although Hispanic individuals had the highest proportion of distant-stage disease at diagnosis, the lowest survival was seen among NHB and NAIAN patients. These groups had comparable stage distributions to others but experienced worse survival even after adjustment for clinical factors, suggesting that systemic inequities beyond disease burden may contribute. Socioeconomic status also demonstrated an independent association with survival, with higher-income patients experiencing better outcomes despite no significant differences in stage at presentation. These findings implicate post-diagnostic barriers such as treatment delays, underinsurance, limited access to high-volume centers, and fragmented care as key drivers of survival disparities (7-10). Prior research has shown that Black and Hispanic patients with iCCA are significantly less likely to receive curative treatments such as surgery or liver directed therapies, which may further exacerbate these inequities (11).
In non-Medicare eligible populations, reliance on Medicaid or inconsistent private coverage can further exacerbate disparities in care through mechanisms such as prior authorization hurdles, restricted provider networks, and high out-of-pocket costs (4). These structural limitations are often compounded by low health insurance literacy, which influences care-seeking behavior. Research indicates that those with greater knowledge of insurance terms and processes are more likely to obtain both preventive and non-preventive care without delay (9). Improved understanding of coverage details including cost-sharing, network limitations, and benefits enhances patients’ ability to access timely care and reduces the likelihood of financial deterrents. As such, efforts to reduce disparities in access and outcomes should not only address policy-level barriers but also prioritize strategies to improve healthcare and insurance literacy across vulnerable populations.
This study has limitations inherent to its retrospective design and use of registry-based data. SEER lacks detailed treatment information, molecular profiles, comorbidity data, and patient-level insurance status, limiting our ability to adjust for important prognostic and access-related factors, especially in a population under 65 years not captured by SEER-Medicare. Previous studies have demonstrated survival differences based on treatment approaches, highlighting the need for further research to understand better how management strategies influence outcomes in patients under 65 years with iCCA. Additionally, SEER covers only about 34.6% of the U.S. population, which may limit national generalizability. Despite these constraints, the large, diverse sample enhances the relevance of our findings to younger patients with iCCA across the U.S.
Conclusions
Our findings highlight the presence of persistent survival disparities among younger iCCA patients, particularly affecting NHB and NHAIAN individuals and those from lower-income groups. These disparities remained significant even after accounting for stage at diagnosis, suggesting underlying systemic barriers to equitable care. Targeted interventions to address access, insurance-related delays, and care fragmentation are urgently needed to improve outcomes in these vulnerable populations.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-411/rc
Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-411/prf
Funding: This work was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-411/coif). M.M.J. serves as an unpaid editorial board member of Journal of Gastrointestinal Oncology from January 2025 to December 2026. A.D. and S.M. are employees of HCA Florida Oak Hill Hospital. The other 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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
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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