Associations between financial toxicity, health-related quality of life, and well-being in Indonesian patients with breast cancer

Patients with cancer worldwide often face considerable financial burdens [1]. The experienced financial challenges can adversely impact their financial well-being, which is the perceived ability to sustain living standards and achieve financial freedom [2]. The term ‘financial toxicity’ (FT) describes the impairment of financial well-being of patients due to cancer diagnosis and its associated care [3]. FT has been reported across many countries, regardless of income levels or healthcare systems [4, 5]. If unaddressed, FT can lead to treatment non-adherence, reduced health-related quality of life (HRQoL), and worse health and survival outcomes [6‐9].

In general, FT can be assessed both objectively and subjectively [10‐12]. Objective FT (OFT) is measured using quantifiable financial metrics (e.g., out-of-pocket expenditure amount or its ratio to household income) or questions on financial coping strategies (e.g., incurring loan and selling assets). Meanwhile, subjective FT (SFT) is the perceived distress arising from the financial burden of their diagnosis and treatment. The measurement of SFT is typically self-reported by the patients using patient-reported outcome measures, such as the COST: A FACIT Measure of Financial Toxicity (FACIT-COST) and Socioeconomic Well-Being Scale (SEWBS) [13, 14].

There is an increasing body of literature exploring the association between FT and HRQoL in patients and survivors of cancer [15, 16]. Significant correlations were found between high levels of both OFT and SFT and reduced overall HRQoL. Specifically, FT has shown associations with a number of HRQoL domains (e.g., social and mental health), measured using instruments such as the European Organization for Research and Treatment of Cancer of Life Questionnaire Core 30 (EORTC QLQ-C30), EQ-5D-5L, Functional Assessment of Cancer Therapy – General (FACT-G), Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and 12-Item Short-Form Health Survey (SF-12) [15, 16]. However, most FT studies have been performed in high-income and English-speaking countries [15, 16]. Further research is needed in low-and-middle-income countries (LMICs) to better understand FT in different cultures and socio-demographic settings [10, 17‐20].

While there has been a surge of FT studies examining its associations with HRQoL, very little is known about the relationship between FT and well-being. There are various definitions of well-being; for example, the World Health Organization defines the well-being construct as a broader spectrum of dimensions compared to HRQoL, which predominantly focuses on physical, psychological, and social domains of health [21‐24]. In an earlier study, SFT was associated with the environment domain of well-being, measured using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) instrument [25]. Evidence suggests that the world is moving toward universal health coverage to ensure access to health care without financial hardship [26]. However, FT persists as a major challenge in oncology care across many countries. A better understanding of the relationships between FT, HRQoL, and well-being may offer valuable insights into how financial challenges relate to various health and well-being domains, helping to shape health and social policies that support patients and their households.

Breast cancer is the most prevalent cancer worldwide, including in Indonesia [27]. Recent findings also suggest that FT in breast cancer occurs in more than twice as many patients in LMICs compared with their high-income counterparts [20]. Indonesia is a middle-income country where cancer is a major cause of mortality and the second costliest chronic disease financed by the country’s single-payer universal health system [28]. Despite the presence of a public health system, patients may face challenges such as underinsurance, which does not cover substantial non-healthcare, cancer-related costs (e.g., transportation to healthcare facilities and caregiver fees), and the uneven distribution of medical professionals and equipment [15].

Therefore, this study aims to investigate the associations between FT, HRQoL, and well-being outcomes in female patients with breast cancer in Indonesia. We hypothesize that FT is negatively associated with HRQoL and well-being.

This study was conducted in accordance with the Indonesian Health Research and Development Ethical Guidelines and Standards [29]. Ethics approval was granted by the Research Ethics Committee of the Hasan Sadikin General Hospital (LB.02.01/X.6.5/284/2023).

The EQ-5D-5L is a generic preference-accompanied measure of HRQoL consisting of two parts [32]. The first part is a descriptive system comprising five single-item dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item has five levels of responses: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems/unable to (5). An EQ-5D-5L health state profile may be described by a five-digit string. For example, ‘11111’ indicates no problems in all dimensions, and ‘22133’ indicates slight problems in the mobility and self-care dimensions, no problems in the usual activities dimension, and moderate problems in the pain/discomfort and anxiety/dimension dimensions. The descriptive system was scored by assigning an index value to each health state profile using the Indonesian EQ-5D-5L value set, with higher values indicating better HRQoL [33]. The second part of the EQ-5D-5L is the EQ visual analog scale (EQ VAS). In this part, patients were asked to indicate their health using a vertical scale which has a value of between 0 (‘the worst health you can imagine’) and 100 (‘the best health you can imagine’). The EQ-5D-5L descriptive system as well as EQ VAS have been widely validated in cancer populations [34‐37].

The EQ-HWB is a newly developed measure that goes beyond conventional measures of HRQoL to include carer- and social care-related quality of life [38]. Development of the measure drew on different theories of well-being including objective lists, preference satisfaction, and capabilities under the extra-welfarist paradigm of measuring social welfare [39]. There are two versions of the measure: a long 25-item form, and a short 9-item form (EQ-HWB-S), which is a subset of the long version [38]. The long form serves a profile measure, while the short form functions a self-classifier for economic evaluations. The items are answered using three different five-level response scales: difficulty, frequency, and severity. The EQ-HWB has earlier been used in cancer populations [40‐43], and was shown to perform well in item response theory and classical psychometric testing [38, 40]. In this study, the patients completed the 25-item EQ-HWB, from which the responses for the EQ-HWB-S were derived. For the EQ-HWB, a level summary score (LSS) was calculated by summing the responses from the 25 items, with higher scores indicating worse health and well-being. The theoretical LSS range of 25–125 was transformed to a scale of 0-100 for analysis. For the EQ-HWB-S, the index value was derived using the UK pilot value set, as no Indonesian value set was available [44]. Higher index values indicated better health and well-being.

The FACIT-COST is the most widely validated and used cancer-specific measure of SFT [13, 18, 45]. The latest version (v2) has 12 items with 0–4 response scale, from ‘not at all’ (= 0) to ‘very much’ (= 4). The items relate to financial adequacy, psychosocial reaction, anticipating future financial problems, and financial hardship on family, among others. The FACIT-COST total score was computed by summing items 1 through 11, with items 2, 3, 4, 5, 8, 9, and 10 scored in reverse. The theoretical score ranges between 0 and 44, with lower scores indicating worse SFT. Following a receiver operating characteristic analysis, a cut-off score of ≤ 17.5 was proposed to indicate high SFT [46].

To assess OFT, the patients were asked if they experienced one or more of the following financial coping strategies in treating breast cancer: (i) withdrawing savings or pension fund, (ii) selling assets such as vehicle, land, and gold/jewelry, (iii) incurring debt from a relative or financial institution, and (iv) closing business. These items were selected based on previous studies [47, 48], while also giving the option to respondents to specify other financial coping strategies using an open-ended ‘other’ response option.

This study aimed to examine the associations between FT, HRQoL, and well-being outcomes in patients with breast cancer. We demonstrated higher SFT to be associated with more problems in EQ-5D-5L pain/discomfort, anxiety/depression, EQ-HWB-S exhaustion, anxiety, sadness/depression, pain, EQ-HWB frustration, discomfort items, lower EQ-5D-5L index value, EQ VAS, EQ-HWB-S index value, and higher EQ-HWB LSS. Higher OFT was also related to more problems in the EQ-HWB-S exhaustion item.

The distress brought about by the financial challenges arising from cancer care was, to some extent, captured by the EQ-5D-5L, EQ VAS, and EQ-HWB. This could be attributed to increased negative emotions related to financial difficulties. Insufficient financial resources may hinder access to optimal healthcare, potentially leading to a diminished HRQoL and well-being [55, 56]. Alternatively, it is also possible that the association is bi-directional as shown by studies using HRQoL to predict SFT [15]. It can be argued that patients with worse HRQoL or well-being subjectively report higher FT due to their condition and possible productivity loss. Hence, complementing the measurement of SFT with OFT seems important for a more comprehensive description of FT by identifying financial metrics or activities of patients.

Our findings suggest that FT accounted for a greater proportion of the variances in well-being, compared to HRQoL. Higher FT could mean that patients may have to make sacrifices in terms of necessities and wants, which may be related to feelings of isolation and frustration. Well-being may better capture the dynamics of FT, as it may include domains broader than HRQoL, such as pursuits that individuals desire or find meaningful, and sense of connection with one’s environment.

Overall, our results align with the existing literature from other countries and neighboring regions. Previous studies conducted in the United States, Australia, and China, focusing on various cancer types such as gastrointestinal, gynecological, and lung, have investigated associations between the SFT (FACIT-COST) and HRQoL as measured by the EQ-5D; employing other diverse methods such as generalized linear model, latent class analysis, and correlations [52, 57‐60]. All the studies demonstrated SFT to be significantly related to lower HRQoL. Additionally, two studies, found SFT to be moderately correlated with well-being [25, 61]. Recent studies have also demonstrated significant associations between FT and EQ-5D-5L pain/discomfort and anxiety/depression domains with comparable association strengths [50‐52], suggesting that FT captures or represents a form of psychological distress, a burden commonly experienced by patients with cancer. Patients with higher symptom burden may experience greater financial strain due to non-medical costs related to symptom management and hospital visits, intensifying their psychological distress.

Our analysis did not reveal a statistically significant association between OFT and the outcome variable across most regression models, despite showing significance in the subgroup comparisons. This suggests that the OFT measurement may have benefitted from a more comprehensive approach, such as the currency amount of out-of-pocket health expenditure, as well as more detailed exploration of the financial coping strategies (e.g., loan amount or receipt from sale of assets). For example, two investigations from China and Malaysia found negative associations between both SFT and OFT with HRQoL [48, 62, 63]. Notably, these two studies consistently measured OFT using the healthcare cost-to-income ratio, while HRQoL was assessed using various instruments: EORTC QLQ-C30, EQ-5D-5L, and FACT-Lung. However, obtaining precise data on actual healthcare costs may present challenges, such as the patient not being completely in charge of their own finances. Recalling the accurate cost amount would also be challenging, particularly in the case of our sample, whose average disease duration since diagnosis was 2.45 years and nearly 100% had insurance coverage that mitigated direct medical expenses, including diagnostic tests, medications, surgeries, and physician fees.

Reflecting on our findings, some policy implications may be considered. While causality has not been established, our findings indicate a significant correlation between higher FT and diminished HRQoL and well-being. Health and social policymakers may consider interventions aimed at alleviating FT. Firstly, it may be important to screen for FT in patients and their families. Through proper identification of those at risk, necessary mitigation strategies can be implemented. One of the most adopted FT interventions involves financial navigation programs aimed at supporting patients and families with managing the financial hardships of their treatment [64‐66]. In the most extreme cases of poverty, extending coverage to include non-medical, cancer-related costs (e.g., transportation and accommodation for outpatients residing at a distance from healthcare facilities) may be an approach. The income-earning capacities of patients should also be protected from disruptions due to cancer [67], such as through employment reintegration programs to facilitate their return to work [68].

This study has some limitations. First, the data were collected from a single center in one country focusing on females with breast cancer. There are also less developed areas in Indonesia with higher poverty rate and lower access to healthcare. Therefore, the results may not be generalized to other types of cancer, male patients, or more resource-poor settings. Second, we solely focused on patients and did not include their caregivers or core family members. In the Indonesian context, men are still predominantly perceived as providers. Our sample primarily consisted of female homemakers and thus, FT may not have been comprehensively captured without the perspectives of the income provider. Third, nearly all patients had insurance coverage that may have led to some socio-demographic covariates not being significantly associated with the outcome variables and excluded from the regressions. However, this could also be attributed to limited response variability. Fourth, our measurement of SFT had its drawbacks. The FACIT-COST was developed in the United States and another measure may be more suited to capture financial well-being in the Indonesian context. However, it is the most widely used cancer-specific measure for SFT, allowing for comparability with previous studies. Fifth, the pilot UK value set was used for calculating the EQ-HWB-S index values, which does not fully reflect the preferences of the Indonesian population. Finally, our study design did not allow us to explore causality, which could be examined in future studies along with potential mediating factors, such as social support.

This is the first study to identify associations between FT, HRQoL, and well-being outcomes in patients with breast cancer, and the first in the FT literature to use the recently developed EQ-HWB instrument to measure health and well-being. Our findings provide additional insight into the burden of cancer and its link to the HRQoL and well-being of patients in a middle-income country context, highlighting the importance of establishing health and social policies aimed at measuring and alleviating FT.