Biliary tract cancers (BTCs) are a rare cancer that make up 3% of all adult cancers, with 11,980 new patient cases and 4,310 deaths in 2021 in the United States, although this number does not include intrahepatic cholangiocarcinomas (1, 2). BTCs most commonly present as gallbladder cancer (GBC), but also include extrahepatic cholangiocarcinoma (ECC), intrahepatic cholangiocarcinoma (ICC). The incidence of GBC is higher among women, who have increased susceptibility to the primary GBC risk factors (i.e., gallstone disease and chronic cholecystitis), as well as among individuals residing in Chile, Japan, and northern India (3). A recent 2019 analysis of worldwide trends in mortality from ICC and ECC showed that ICC incidence and mortality have increased in recent years (4). GBC makes up approximately two-thirds of BTCs and remains the most aggressive of the BTCs with the shortest median survival duration (5).

Patients affected by BTCs are usually diagnosed at late stages of disease due to the rapid onset and asymptomatic nature of early disease, or potential misdiagnosis as biliary colic; late diagnosis often results in poor prognosis (6). Surgery remains essential for a curative approach, although data from the SEER registry indicates that the overall 5-year-survival is estimated to be 10% across all patients (7). The postoperative median overall survival estimated to be 18-30 months is based on the BILCAP clinical trial with adjuvant capecitabine now being the standard of care, and patients with positive lymph node status and resection margins were reported to have a worse prognosis (8, 9). National Comprehensive Cancer Network (NCCN) guidelines recommend multimodality therapy for all patients diagnosed with node-positive resected cholangiocarcinoma, specifically systemic chemotherapy with or without targeted radiation (10, 11). Both chemotherapy and chemoradiation have been associated with improved survival outcomes in BTC patients with lymph node-positive disease (12). Furthermore, methods to improve BTC treatment such as tumor genetic profiling have increased over the last decade and led to the approval of IDH1 and FGFR2 inhibitors (13–15). On the other hand, however, addition of certain emerging therapies such as anti-EGFR monoclonal antibodies to existing therapeutic regimens and immunotherapy have not significantly improved overall and progression-free survival (16).

Since cholangiocarcinoma remains such a challenge to the field of oncology due to its poor prognosis and difficult course of treatment, equal access to and receipt of proper treatment is of paramount importance. Although racial disparities in the diagnosis, incidence, and time to treatment of hepatobiliary cancers have been investigated in recent years, there is still limited data on the association of racial and ethnic category in the receipt of NCCN-concordant treatment for resected high-risk BTCs (17). Based on the recently reported disparities in receipt of surgery, quality of lymph node clearance post-resection, and unequal improvements in overall survival and incidence rates of BTCs, our aim was to investigate the associations between race, ethnicity, and socioeconomic factors on the receipt of treatment aligned to NCCN guidelines for high-risk BTC using the National Cancer Database (NCDB). For the purposes of this study, the term concordance indicates the extent to which patients received a treatment that was recommended by NCCN guidelines.

Our analysis of the NCDB database is the first to reveal that Hispanics are less likely to receive NCCN guideline-concordant treatment for high-risk BTC. Consistent with more recent literature, not receiving adjuvant therapy for high-risk BTC correlates with worse outcomes (8, 18). Overall, 29.7% of patients did not receive treatment in accordance to NCCN guidelines, with Hispanic patients (36.1%) having the highest proportion of non-concordant care — approximately a 20% increase above White patients. On multivariate analysis, Hispanic ethnicity remained significantly related to receiving treatment that was non-concordant with NCCN guidelines.

It should be noted that the term “adherence” indicates the extent to which patients voluntarily followed through with NCCN guideline-concordant treatment prescribed by their health care providers. This is in contrast to the term “compliance,” which suggests that the patient is passively following the practitioner’s orders and implies lack of partnership between provider and patient in determining the patient’s treatment plan (19). We are currently unable to determine if concordance to NCCN guidelines or lack thereof is due to factors associated with clinician, the patient, or both, as adherence is a very complex and multifaceted issue that is beyond the scope of this study. Potential factors that may influence NCCN-concordant treatment for BTCs may involve clinician bias, healthcare provider opinion on eligibility of patients to receive NCCN recommended treatment, hesitancy toward chemotherapy treatment, and logistical abilities of the healthcare system as well as the patient and their loved ones to maintain a prescribed treatment regimen.

There is existing evidence of racial and ethnic and socioeconomic disparities in the treatment of other hepatobiliary cancers. In a recent evaluation of GBC patients from the 2000–2013 SEER registry, Black patients were less likely to receive surgery when compared to White patients. Furthermore, Hispanic patients were less likely to have optimal lymph node clearance post-resection when compared to White patients (20). In another evaluation of the 2001–2012 SEER database, overall survival in GBC has improved in all racial and ethnic groups, except for Hispanic and Black patients. Hispanic individuals also exhibit the highest incidence rates of gallbladder cancer, and incidence rates in Black individuals are on the rise (21). Additionally, a recent study analyzing 13,965 patients from the NCDB concluded that the odds of CCA in admitted patients were higher for the Hispanic population (22). The study also noted that Hispanic patients did not display different propensity-matched odds of inpatient mortality, morbidity, hospital length of stay, or resource utilization compared to non-Hispanic patients. In a study analyzing the Nationwide Inpatient Sample database between 2005-2014, patients that received surgery for intrahepatic cholangiocarcinoma were typically White, in a younger age cohort, privately insured, less burdened by comorbidities, and more likely to be treated in hospitals located in urban rather than rural geographical areas (23). Furthermore, a recent study identified 12,095 patients with cholangiocarcinoma through the NCDB, concluding that Black patients had lower odds of receiving surgery when compared to White patients (odds ratio [OR] 0.66l; P <.001). The same study also concluded that there were no racial and ethnic or socioeconomic differences in receipt of multimodality therapy once patients accessed surgical care, however (17). A study using 1995-2014 SEER registry showed that although Black patients had a lower incidence of intrahepatic CCA (iCCA), these patients had higher mortality than their White counterparts. This study also highlighted a higher incidence of iCCA amongst Hispanic patients as well as worse all-cause mortality and iCCA specific mortality in Hispanic patients compared to non-Hispanic patients (24). However, our study provides additional findings regarding ethnic disparities in the Hispanic population that have not yet been mentioned in the literature. These differences are likely due to our focused inclusion criteria for analysis in the NCDB, which specifically included BTC patients who underwent surgery and were found to have metastatic lymph nodes or positive surgical margins from 2004 to 2014.

Hispanic persons may receive less appropriate care for several reasons. Notably, our data revealed that Hispanic patients were less likely to be insured (with approximately 85% coverage rather than 95% in other races/ethnicities), less likely to be treated at an academic facility, and had additional comorbidities when compared to White patients. These findings are significant in the context of available disparities research in other gastrointestinal cancers. The significance of insurance coverage was also shown in a previous study for HCC which noted that insurance status had the most profound effect on the likelihood of surgical treatment in patients with HCC (25). In a study investigating pancreatic adenocarcinoma, uninsured patients and patients with Medicaid insurance were less likely to receive adequate treatment and surgery than patients with private insurance, although in our study we did not find any significant association with insurance status (26). Another study investigating colorectal cancer revealed that underinsured individuals also have increased comorbidities and are less likely to have access to quality care as a result (27).

Although the current study lacks the ability to provide concrete solutions to the issues presented, we introduce the discovered disparities with optimism, as identification of an issue is the first step to improvement. The findings of this study could provide a basis for future disparities research to be conducted, with the end goal being equity in clinical evaluation and treatment of patients with BTC regardless of race, ethnicity, Charlson-Deyo Comorbidity Index, or socioeconomic factors. Potential first steps to alleviating this problem in healthcare would be a study evaluating the deductive reasoning process oncologists utilize when prescribing treatments for patients diagnosed with BTCs. Another potential approach to addressing the presented disparities would be a study evaluating the potential implicit biases and attitudes toward race, ethnicity, socioeconomic factors, and comorbidities in oncologists involved in the diagnosis and treatment of BTCs. This study does not capture the complexity of decision-making and the role of patient versus provider in lack of concordance to NCCN guidelines. Future studies are needed to explore these issues by evaluating factors influencing both providers and patients.

The limitations of our study mainly involve pre-existing limitations in the NCDB database. While the NCDB database represents more than 70% of newly diagnosed cancer cases nationwide (including over 34 million historical records), 30% of patient data is still missing. Second, the NCDB database lacked information regarding the functional status of patients and severity of co-morbidities, which are important factors in deciding whether to recommend adjuvant chemotherapy. Furthermore, utilizing a retrospective database automatically integrated selection bias into our study. The patients included in the NCDB have already overcome several barriers to healthcare access; thus, the dataset provided by NCDB inherently excluded patients who did not have the resources or opportunity to be treated at a participating cancer center. Additionally, distance to cancer centers and transportation are not captured in the NCDB but may play an important role in treatment location. It is also of paramount importance to acknowledge that this study was unable to capture the multitude of additional factors that contribute to disparities. Finally, the current study is not able to understand the absolute root cause of these racial disparities, and as a result we are unable to offer tangible solutions that will benefit Hispanic and Black patients.

In summary, this study revealed that Hispanic patients with high-risk BTC were significantly more likely to receive non-concordant care when compared to White patients in regards to NCCN guidelines. These findings are consistent with recent studies revealing additional disparities in Hispanic and Black persons related to the diagnosis, incidence, and time to treatment of hepatobiliary cancers. The findings of this study could help identify high-risk BTC patients who are most likely to not receive adjuvant treatment as recommended by NCCN guidelines, and more importantly, patients who are at an increased risk of suffering from higher rates of morbidity and mortality due to unequal access to and receipt of cancer treatment. Additional research is needed to confirm and understand the observed disparities and guide targeted interventions, with the ultimate goal of eliminating disparities in healthcare.

The datasets presented in this article are not readily available because the data that support the findings of this study are available from the American College of Surgeons—Commission on Cancer. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the authors with the permission of the American College of Surgeons—Commission on Cancer. Requests to access the datasets should be directed to https://www.facs.org/quality-programs/cancer/ncdb.

LH—investigation, methodology, writing—original draft, and writing—review and editing. AH—investigation, methodology, writing—original draft, and writing—review and editing. GC—conceptualization, formal analysis, investigation, methodology, writing—original draft, and writing—review and editing. AA—formal analysis, writing—original draft, and writing—review and editing. T-YT—writing—review and editing. LO—writing—review and editing. NP — formal analysis, methodology, and writing—review and editing. DB—writing—review and editing. JS—writing—review and editing. AM—writing—review and editing. ES—writing—review and editing. MH—writing—review and editing. JB-S—conceptualization, formal analysis, investigation, methodology, writing—original draft, and writing—review and editing. RL—conceptualization, formal analysis, funding acquisition, investigation, methodology, project administration, resources, supervision, writing—original draft, and writing—review and editing. All authors contributed to the article and approved the submitted version.

This work was supported by University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center.

The published content and conclusions are the responsibility of the authors and does not represent the views of The American College of Surgeons and the American Cancer Society.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.