Financial toxicity in patients with newly diagnosed hepatocellular carcinoma: a cross-sectional study

Introduction

Financial toxicity (FT) in cancer refers to the economic burden and distress experienced by patients and their caregivers associated with cancer care access and use, ranging from costs that are more direct—such as the out-of-pocket expenses for diagnostics or therapeutics—to indirect, including those incurred from travelling to points of care or loss of income from time spent away from employment receiving or recovering from care (1,2). In a recent systematic review encompassing more than twenty thousand patients, FT was reported by nearly half of all patients with cancer (3), with similar estimates reported specifically in the United States (U.S.) (4). FT among patients with cancer has been associated with significantly worse outcomes, including higher medication non-adherence, poorer quality of life (QOL), and even greater mortality (5,6).

Significant variations in both objective costs and patient-reported FT exist across cancer types (7,8). However, only one study based out of China has, to our knowledge, examined FT specifically in hepatocellular carcinoma (HCC) and found approximately half of all patients experienced catastrophic financial burden, defined as yearly out-of-pocket expenses ≥40% of household annual income (9). However, no study to our knowledge has yet to evaluate patient-reported measures of FT in HCC. We thus sought to assess patient-reported FT via a validated survey instrument among patients with newly diagnosed HCC as well as identify patient-, disease-, and treatment-related factors associated with FT in HCC. We present this article in accordance with the SURGE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-287/rc).

Methods

All patients with newly diagnosed HCC and without prior treatment history were approached by a study team member for enrollment during their visit at a single multidisciplinary liver cancer clinic at Beth Israel Deaconess Medical Center—a tertiary care center in Massachusetts, U.S.—between January 2023 and November 2024. Eligibility criteria included ≥18 years of age and primary language being English, Spanish, or a Chinese dialect (Mandarin or Cantonese); patients were excluded if they had previously received HCC-directed treatments. Interpretation services were used for patients whose primary language was either Spanish or Chinese. No incentives for participation were provided.

The Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) (10), a validated survey instrument for evaluating financial distress among patients with cancer (range, 0–44; lower scores reflect worse financial wellness), was completed electronically by study participants during their initial visit. Baseline sociodemographic (age, sex, race, ethnicity, primary language, insurance status, employment status, marital status, highest education completed, household income, living arrangement, zip code) characteristics were self-reported by patients, while other clinical [performance status, Barcelona Clinic Liver Cancer stage, age-adjusted Charlson comorbidity index, albumin-bilirubin score, presence and etiology of chronic liver disease, Child-Pugh grade, Model for End-Stage Liver Disease (MELD)-Na score] and planned treatment (surgery, liver-directed therapy, systemic therapy, clinical trial enrollment) characteristics were evaluated by medical record review. Patients additionally completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-HCC18 (11), a validated tool for evaluating patient-reported QOL in HCC. Area Deprivation Indices (12,13), representing percentile rankings of neighborhoods by socioeconomic disadvantage with higher values reflecting greater disadvantage, were calculated using patients’ home zip codes. A time from diagnosis to initial multidisciplinary clinic assessment of ≥60 days was considered a significant delay (14).

Statistical analysis

Mean baseline COST-FACIT scores were compared using two-sided t-test for binary variables and one-way analysis of variance (ANOVA) for non-binary variables. Shapiro-Wilk test was performed to confirm normal distribution of baseline COST-FACIT scores (P=0.34). On exploratory analyses, COST-FACIT scores of 0–13, 14–25, and ≥26 were categorized as representing moderate-severe, mild, or no FT, respectively (15-18). Differences in patient, disease-, and treatment-related factors by degree of patient-reported FT were determined via Chi-squared or Fisher’s exact tests. For analyses comparing characteristics between responders vs. non-responders to the COST-FACIT survey, t-tests were performed for continuous variables and Chi-squared or Fisher’s exact tests for categorical variables. Missing data were excluded without imputation.

All research was conducted in accordance with both the Declarations of Helsinki and its subsequent amendments and Istanbul. Informed consent was obtained from each participant or each participant’s guardian and approval for this study was obtained from the study site’s institutional review board at Beth Israel Deaconess Medical Center (approval No. 2022P000755).

Results

Among the 50 patients enrolled, 38 (76%) completed the baseline COST-FACIT survey. Figure 1 illustrates the derivation of the study analytic sample. Comparisons between responders and non-responders of the survey are presented in Table S1. Excluding QOL which could not be compared as all 12 non-responders additionally did not respond to the EORTC QLQ-HCC18 survey, the only statistically significant difference was in the age-adjusted Charlson comorbidity index with median values of 5.5 and 3.5, respectively.

Figure 1 Derivation of study analytic sample. COST-FACIT, Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy.

Table 1 presents baseline characteristics of the study cohort. The median age was 68 years, over one-third were female, and the majority were of White race and non-Hispanic ethnicity. Additionally, all but 3 (7.9%) participants had documented public or private health insurance, 11% were unemployed, 47% were not married or partnered, 29% reported a household income of <$50,000, and 18% lived alone. All but three (7.9%) patients in our cohort had a prior history of chronic liver disease of one or more etiologies, with the most common causes being hepatitis C (37%), alcohol (37%), metabolic (29%), and hepatitis B (16%); 82% of participants had known cirrhosis (Table 2). With respect to planned treatment modalities, 82% were planned for liver-directed therapy, but only 13% and 24% for surgery and systemic therapy, respectively; only 8% were enrolled in a clinical trial (Table 3).

In our study cohort, the mean COST-FACIT score was 26 (standard deviation, 11) and 17 (45%) patients reported any degree of FT (i.e., COST-FACIT score <25). We found younger age (<65 vs. ≥65 years; mean, 21.2 vs. 28.6; P=0.04), Hispanic ethnicity (Hispanic vs. non-Hispanic ethnicity; mean, 16.1 vs. 27.3; P=0.05), non-English primary language (non-English vs. English; mean, 16.2 vs. 27.6; P=0.03), lack of employment (not employed vs. retired vs. employed; mean, 15.5 vs. 30.5 vs. 24.8; P=0.03), less completed education (high school or earlier vs. college or beyond; mean, 23.0 vs. 32.6; P=0.01), worse self-reported QOL (EORTC QLQ-HCC18 score > cohort median vs. ≤ cohort median; mean, 22.1 vs. 29.3; P=0.04), and no plan for surgical treatment (no plan vs. plan for surgical treatment; mean, 24.6 vs. 35.6; P=0.03) were associated with significantly worse COST-FACIT scores (Table 4). Although not statistically significant, lower household income (<$50,000 vs. $50,000–$99,999 vs. ≥$100,000; mean, 25.0 vs. 23.1 vs. 33.0; P=0.09) trended towards worse patient-reported FT.

On exploratory analyses limited by sample size categorizing COST-FACIT scores to represent moderate-severe, mild, or no FT based on previously reported ranges, non-English primary language was the only factor significantly associated with worse FT (P=0.03) (Table S2). When assessed as a binary outcome of no vs. any (i.e., mild or moderate-severe) FT, primary language was not significantly associated with FT (P=0.15) however less completed education (P=0.08) and no plan for surgery (P=0.053) trended towards significantly worse financial wellness.

Discussion

In this cross-sectional study of patients with newly diagnosed hepatocellular carcinoma presenting for initial multidisciplinary evaluation prior to cancer-directed treatment, we found nearly half of all patients endorsed FT, with younger age, Hispanic ethnicity, non-English primary language, lack of employment, less completed education, and no plan for surgical treatment being significantly associated with worse patient-reported FT. Greater FT was additionally associated with significantly worse patient-reported QOL. Although the study design limits the ability to make causal inferences, this is the first study to our knowledge to investigate patient-reported FT in HCC.

The literature surrounding HCC-associated FT has to date been limited to a single prior study. Among 131 patients with HCC in China, 66% of patients reported catastrophic HCC-related healthcare expenses prior to insurance reimbursement which improved to only 50% following reimbursement receipt (9). Although it is difficult to generalize these findings to the U.S. given the significant international differences in healthcare system structures, a recent scoping review comprised predominantly of U.S.-based studies similarly found that patients with chronic liver disease experience high rates of FT that translate to worse outcomes for both patients and their caregivers, including decreased care adherence and access as well as greater housing and food insecurity (19). Our findings indicating a high prevalence of FT among patients with HCC are in line with prior studies of FT in non-HCC cancers and additionally highlight key sociodemographic characteristics—including younger age, Hispanic ethnicity, non-English primary language, lack of employment, and lower educational attainment—associated with worse outcomes.

Although FT has been well-established to be associated with worse cancer outcomes, there is a clear paucity of studies outlining and evaluating appropriate interventions (20). Patient-provider engagement in comprehensive discussions about cancer care costs have been associated with a one-third decrease in out-of-pocket expenses without significant changes in receipt of required care, however only 10% of patients with cancer report having participated in such discussions (21). Importantly, patients largely report being open to conversations about cancer care costs (22,23) and emerging evidence indicates such conversations may even improve subjective financial wellness (24). Given recent survey data indicating 41% of oncology providers rarely or never address care-related costs with the most frequently cited barrier being lack of knowledge or resources (25), further efforts are needed to better equip physicians in facilitating these sensitive but critical discussions. At Beth Israel Deaconess Medical Center, patients noting FT are offered referrals to speak with a financial counselor. The role of financial counseling services in cancer care remains an important area of further exploration given that physicians are oftentimes not equipped to navigate these discussions and patients have been shown to prefer discussing financial concerns with care team members other than their physicians (26,27). Specific patient populations potentially at greater risk for FT—such as younger age, Hispanic ethnicity, non-English primary language, lack of employment, and lower educational attainment as we found in our study—may benefit from the development and evaluation of targeted interventions, such as incorporation of social work and other psychosocial specialists into routine oncologic care (28,29). On a macroscopic level, identifying and implementing changes in overarching policies and legislature related but not limited to healthcare access and managing exorbitant out-of-pocket costs disproportionate to patients’ financial resources are highly needed (30).

Strengths of this study include the diversity of the study cohort, with more than one-third being of female sex, almost half not married or partnered, almost one-third reporting a household income of <$50,000, and the inclusion of non-English-speaking patients whose primary language was Chinese or Spanish. We additionally examined a wide breadth of sociodemographic, disease, and planned treatment characteristics, allowing for broad hypothesis-generating analyses. Our study is not without limitations. We performed a single-site study of patients presenting to a multidisciplinary clinic at an academic tertiary care center and thus may not be generalizable to patients in other settings. Over 90% of our cohort additionally had documented public or private health insurance and thus our results may not extend to those without insurance coverage who would be a higher risk for experiencing FT. Furthermore, important psychosocial variables—such as presence and degree of caregiver burden as well as availability and receipt of external financial support—were not accounted for and limits the comprehensiveness of this analysis. The smaller size of the study cohort limits the ability to conduct multivariate analyses to assess for independent contributions of baseline characteristics to FT. Of the 50 patients enrolled in this study, 12 (24%) did not complete the COST-FACIT survey for unknown reasons. Although there is thus the potential for non-response bias, only the Charlson comorbidity index was statistically significantly different between responders and non-responders with values of 5.5 and 3.5, respectively; however, these likely do not reflect clinically significant differences given that they correspond to similar 10-year survival estimates of 95% and 92%, respectively, and thus likely approximate similar overall comorbidity burdens. Finally, as we measured FT prior to treatment initiation, our study does not inform on how it may change during the treatment course and into cancer survivorship. However, efforts are currently underway to longitudinally follow our study cohort to assess the course of patient-reported FT throughout treatment and its associations with treatment adherence and survival.

Conclusions

In conclusion, we found FT was reported by nearly half of all patients with newly diagnosed HCC even prior to treatment initiation, with patients who are younger, of Hispanic ethnicity, report a non-English primary language, are not employed, have completed less formal education, or are not planned for surgical treatment experiencing greater FT. Our findings underscore a need for further efforts to develop and integrate interventions targeting improving financial wellness among patients with HCC.

Acknowledgments

Findings from this work were previously presented at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium 2025.

Footnote

Reporting Checklist: The authors have completed the SURGE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-287/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-287/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-287/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-287/coif). A.J.B. reports institutional research funding from Geistlich Pharma, Agenus, Ipsen, Panova, Oncomatryx, AstraZeneca, Seagen, and Consulting or Advisory from Sirtex, Agenus. M.L.B.P. discloses research funding from NIH/NCI (K08CA248473) and institutional research funding from Nucana, Genentech, AstraZeneca, and Helsinn Therapeutics, as well as personal stock holdings in Lilly, Medtronic, P&G, Merck, and Agios. 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. All research was conducted in accordance with both the Declarations of Helsinki and its subsequent amendments and Istanbul. Informed consent was obtained from each participant or each participant’s guardian and approval for this study was obtained from the study site’s institutional review board at Beth Israel Deaconess Medical Center (approval No. 2022P000755).

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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