Financial toxicity and employment status in cancer survivors. A systematic literature review

Background Financial toxicity has traditionally been attributed to the rising costs of cancer care. As ability to work impacts one’s financial situation, limited employment and reduced income may also contribute to financial toxicity. We examined evidence of the association between financial toxicity and employment status in cancer survivors. Methods A systematic literature review was performed via PubMed, Web of Science, CINAHL, and PsycINFO with search terms including “Cancer,” “Financial toxicity,” and “Employment” on September 25, 2019. Results Thirty-one papers met eligibility criteria. Thirteen studies were rated as having high quality, 16 as adequate, and two as low. Being actively treated for cancer had serious negative consequences on employment and medical expenditures. Unemployment, changed or reduced employment, lost days at work, poor work ability, and changes to employment were associated with a higher risk of financial toxicity. Patients who were younger, non-white, unmarried, of low education, living with dependents, residing in non-metropolitan service areas, with lower income, and of low socioeconomic status were more at risk of financial toxicity. Other variables associated with financial toxicity included having a mortgage/personal loan, higher out of pocket costs and household bills, limited health insurance, more severely ill, on active treatment, and lower functioning or quality of life. Conclusion Cancer negatively affects employment, and these changes are significant contributors to financial toxicity. Researchers, healthcare professionals, and patients themselves should all cooperate to tackle these complex issues.


Introduction
Financial toxicity refers to the financial burden or financial hardship experienced by cancer survivors because of cancer and its treatment [1][2][3]. The problem of financial toxicity is increasing since the costs of care are increasing with newer treatments, the prevalence of cancer is growing rapidly, and many survivors live with cancer as a chronic disease. Depending on the country and thus the healthcare system, financial toxicity prevalence varies widely, but studies have shown consistently that its presence is associated with lower quality of life, poorer adherence to or delay of care, and early mortality [4][5][6][7].
High costs of cancer care are a recognized cause of financial toxicity through medical costs (such as cost of new treatments), non-medical costs (e.g., travel costs to hospitals), or indirect costs (e.g., lost wages as a result of time off work for cancer treatment) [5]. Even if healthcare is available to everyone via universal health insurance coverage, patients have outof-pocket expenses (OOP) in relation to their disease and its treatment. Since many cancer survivors are known to experience long-term side effects and symptoms of cancer and its treatment, these costs can continue even years after diagnosis [8].
To date, a number of systematic reviews have examined financial toxicity in cancer survivors [2,9,10]. A recent review summarized 45 studies and concluded that 47-49% of cancer survivors reported some degree of financial distress [9]. Another recent review examined 25 studies from nine countries with the majority from the USA and showed that up to 73% of patients reported financial toxicity [2]. Predictors of financial toxicity included younger age, female gender, a more recent diagnosis, and use of adjuvant therapies [2]. A review that focused on the relationship between financial toxicity and symptom burden concluded that a clear association exists between financial toxicity and psychological symptoms like depression [10].
While the focus on financial toxicity has historically been on the costs of cancer care, especially in light of the significant rise in the cost of cancer medicine [11], limitations in or inability to work is also likely to contribute to financial toxicity [2,9]. Both income and changes in work participation have been associated with financial toxicity [2]. Similarly, reduced income and missed days of work due to illness are associated with financial hardship [9]. Data on employment after cancer show that as many as 40% of employed cancer survivors do not return to work after cancer diagnosis [12], and inability to work is associated with greater financial hardship and reduced quality of life [6]. Those more likely to return to work after diagnosis are individuals with a higher educational level, male gender, and younger age at diagnosis; those that underwent less invasive surgery, experienced fewer physical symptoms, and had a lower length of sick leave; and those with provision of workplace accommodations such as flexible hours or rehabilitation services, lower length of sick leave and continuity of care [13]. This significant overlap between predictors of financial toxicity and predictors of unemployment after cancer raises the question of how employment status and financial toxicity after cancer are related, taking into account a possibility of confounding.
To address this question, the primary aim of this systematic literature review was to examine the relationship between financial toxicity and employment in cancer survivors and any variables that may affect this relationship.

Search strategy
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14]. A computerized search of the literature through the search engines PubMed, Web of Science, CINAHL, and PsycINFO was performed on September 25, 2019. The search terms captured concepts of "financial toxicity," "employment," and "cancer." Boolean operators and keywords were used with Medical Subject Headings (MeSH) where possible. Separate searches were conducted for each database. All search results were imported in EndNote, which was used to remove duplicates. Reference lists of all identified publications were checked to retrieve other relevant publications not identified by means of the computerized search.

Inclusion and exclusion criteria
Studies that met the following criteria were included: (1) if the objective was to describe financial toxicity and employment in adult cancer survivors, (2) if the publication described a quantitative study, (3) if the publication was an original article (e.g., no poster abstracts, editorials, reviews, and letters to the editor), (4) if they were published or in press in peerreview journals, and (5) if they were written in English. Studies were excluded for the following reasons: (1) if they included participants under the age of 18; (2) if they focused solely on spouses, caregivers, family of cancer survivors, or health professionals; or (3) if they included patients with other diseases besides cancer as well.

Screening
Articles were reviewed by title and abstract according to the pre-specified inclusion and exclusion criteria. Then full-text papers were reviewed to confirm eligibility. Results of the search were discussed, and any discrepancies were clarified until consensus was reached. A flowchart of this selection procedure is shown in Fig. 1.

Quality assessment
The methodological quality of all included articles was assessed according to predefined criteria using a 13-item standardized checklist. The checklist was a slightly adapted version of an established criteria list for systematic reviews [15,16]. The criteria are presented in Table 1.
Each item of an article that matched our criteria received one point. Zero points were assigned if an item did not meet our criteria, was described insufficiently, or not at all. The highest possible score was 13. Studies scoring ≥ 75% of the A description is included of at least two socio-demographic variables 31 4 A description is included of at least two clinical variables 30 5 Inclusion and/or exclusion criteria are described 28 6 Participation rates for patient groups are described and are > 70% 10 7 Information is given about the degree of selection of sample (e.g., whether there is a selective response) 9 Study design 8 The study size is consisting of at least 50 participants (arbitrarily chosen) 31 9.
The collection of data is prospectively gathered 8 10. The process of data collection is described (e.g. interview or self-report) 30 Results 11. The results are compared between two groups or more (e.g., comparison with healthy population and differences in financial toxicity between those with or without work), and/or results are compared between at least two time points (e.g., pre-versus post-treatment) 30 12. Statistical proof for the main findings is reported 30 13. Relationship between financial toxicity and employment status is described 23  maximum attainable score (≥ 10 points) were, arbitrarily, considered to be of "high quality." Studies scoring between 50 and 75% (7-9 points) were rated as "adequate quality." Studies scoring lower than 50% (i.e., < 7 points) of the maximum attainable score were considered to be of "low quality."

Quality of studies
The quality of 13 studies included in the review was arbitrarily rated as high, while 16 studies were rated as adequate quality and two as having a low quality ( Table 2). The primary limitations of the studies were the lack of information about the degree of selection of the sample (e.g., whether there is a selective response), the cross-sectional research designs, and the lack of a validated financial toxicity measure and/or lack of objectively assessed financial toxicity.

Financial toxicity and employment among cancer survivors versus a normative population
Four studies were identified that compared employment between those with a cancer diagnosis and those who have not had cancer [8,20,24,37]. The results of 3 cross-sectional American studies showed that, among those < 64 years of age, being actively treated for cancer decreased the probability of employment [20], and increased employment disability [8], the number of missed workdays per year [8,20,37], the number of days spend in bed [8,37], and the mean annual medical expenditures [8,20,37], compared with those not having cancer. A longitudinal Australian study compared financial strain between cancer survivors and the general population and concluded that although financial strain was higher in survivors compared with controls 6 months after diagnosis, it eased and was comparable with the general population at 12 months post-diagnosis [24].

The relationship between financial toxicity and employment
The effect of cancer on financial toxicity and employment among cancer survivors was examined in all studies. The quantitative results are summarized in Table 2. Increased financial toxicity was associated with both unemployment, changed or reduced employment, lost days at work, or poor work ability in almost all included studies [8, 18-22, 24-30, 32-34, 38, 40, 42, 43, 45, 46]. However, a single study from Ireland identified employed individuals at greater risk for financial toxicity since they are more likely to experience a drop in income due to cancer [41]. Measures of financial toxicity varied strongly in these studies.
Examining only those studies that measured the impact of unemployment or ceasing work on financial toxicity identified twelve studies [18,21,24,29,30,33,38,40,[45][46][47]. Half of the studies examining the impact of unemployment or ceasing work on financial toxicity have been conducted in the USA [24,29,30,38,[45][46][47], only two conducted in Australia [23,24], and one in Germany [18], the Netherlands [33], Iran [21], and Japan [40]. Across cancer types, those who were unemployed or ceased employment experienced greater financial toxicity [18,21,24,29,33,40,45,46], objective financial burden (e.g., large decrease in income, selling/second mortgage on home, withdrawing money from retirement accounts, or bankruptcy) [29,38,48], or expenses [30] than patients who remained employed following their diagnosis. In contrast, an Irish study among breast and prostate cancer survivors reported that those who were not working had a significantly lower risk of cancer-related financial stress compared with those working (relative risk = 0.71, 95%CI 0.58-0.86) [41]. A study from the USA including a mixed group of cancer survivors concluded that survivors employed at diagnosis who took extended leave or switched to part-time work were more likely to report financial hardship (49%) compared with those employed that did not make changes (20%) and those who were not employed at diagnosis (17%) [43]. One study reported that unemployment was significantly associated with financial hardship while retirement was associated with decreased odds of financial hardship [46].

Employment factors associated with financial toxicity
Studies analyzing employment factors associated with financial toxicity showed that those experiencing less financial toxicity had the following characteristics: paid leave [17], those who returned completely to work [21], not working [41], retired [41], privately insured [41], and those with higher household savings. Also, a higher age at diagnosis [40], being white [36,43], a longer time since diagnosis [23,38,43], a lower disease stage [35], and a higher educational level [33,39,40] decreased the chance of financial toxicity.

Discussion
This literature review identified a modest number of studies examining the relationship between financial toxicity and employment indicating relative scarcity of data on this subject. In general, cancer survivors can lose their job, they may have limitations in the amount or kind of work, they can experience job lock (not being able to take promotions or switch jobs) due to concerns of changing healthcare insurance, and they can experience higher cost-sharing when insured (especially in the USA) which can all contribute to financial toxicity. More research in this area is warranted since data varies between countries according to differences in healthcare and health insurance systems.
Unemployment, changed or reduced employment, lost days at work, or poor workability and changes to employment were associated with a higher risk of financial toxicity. However, a single study identified employment as a risk factor for financial toxicity among breast and prostate cancer survivors in Ireland [41]. This finding may reflect differences in health and social care systems [41]. In Ireland, the healthcare system consists of both private and public systems with an income limit determining acceptability for public services [50]. Those that are above the income limit are not accepted for public services and therefore pay for private healthcare. People with private care had higher costs compared with those in the public system, which suggests that employed individuals may be more susceptible to greater healthcare costs and therefore financial strain.
The relationship between negative work changes, and financial toxicity can be partly explained by the link between employment and health insurance. In some countries, like the USA, health insurance is often closely linked with employment. Therefore, losing one's job because of cancer entails losing one's health insurance. These two factors combined are a major risk factor for financial toxicity. However, some studies showed a negative association between work changes and financial toxicity in the setting of the universal healthcare coverage [24,33]. This suggests that the association of employment and financial toxicity is not only a function of health care insurance but of social security systems as well. However, health insurance has an important role since those with private health insurance and paid leave often experienced a lower risk of financial toxicity while those with public insurance, those uninsured, those with poor insurance coverage, and those with a lack of substantial prescription drug coverage reported a higher risk of financial toxicity.
Differences between countries in employment and financial toxicity can also be caused by "return to work after cancer" policies. Return to work is influenced by social security systems, especially the length of paid sick leave. Furthermore, differences in legislation, incentives, and possibilities of an employer to provide employees with return to work programs differ among countries.
Besides negative work changes, being younger, non-white, unmarried, of lower education status, and residing with dependents or in non-metropolitan service areas were predictive of a higher risk of financial toxicity. Other factors associated with a higher risk of financial toxicity were having lower incomes, low socioeconomic status, a mortgage/personal loans, higher OOP costs and household bills, non-optimal health insurance, lower functioning and quality of life, and being more severely ill or on active treatment. This is not surprising since financial toxicity is a burden often affecting those most disadvantaged. These people often have fewer financial reserves or support on which to draw in times of unexpected financial strain. Also, these factors are often negatively associated with employment as well and therefore may have a compound effect on the likelihood of financial toxicity. Addressing financial toxicity may assist in addressing issues of access to care, equity of care, and may have significant impact on outcomes.
Only four studies compared survivors with a normative population. Three cross-sectional studies from the USA concluded that being actively treated for cancer had serious negative consequences regarding employment and medical expenditure. However, one longitudinal Australian study reported differences in financial strain at 6 months but no differences at 12 months after diagnosis. Time since diagnosis is thus an important is variable to consider but not all studies take this into consideration.
This systematic review has several strengths including a broad search of multiple keywords and search terms across various databases. The quality of most of the studies, as rated by a wellvalidated tool, was moderate to high. There were also a number of limitations to our study, which should be considered. We specifically targeted studies of adult cancer survivors excluding parents, siblings, caregivers, and spouses of cancer survivors. This has restricted the extent to which household financial toxicity can be examined and its relation to employment, although the impacts of financial toxicity are seen to extend to the parents, spouses, and caregivers of survivors [42]. Also, we did not include fully qualitative studies. In addition, we only focused on English language literature. Moreover, most studies were from a selected number of countries which limit generalizability across other countries or healthcare systems. Despite these limitations, this review is the first to explore the relationship between financial toxicity and employment among cancer survivors.
cThis review demonstrates the relative paucity of studies in the area of financial toxicity and employment and highlights a need for further research into the variables that are associated with the relationship between financial toxicity and employment to inform development of interventions to reduce financial toxicity because of employment change. For instance, the variation by cancer type, treatment type(s), duration of treatment(s), healthcare provider, and the role of community, state, and federal policy factors associated with financial hardship are still unclear. Further research should have a longitudinal design in order to focus on how the relationship between financial toxicity and employment changes over time. In addition, the use of a control group is warranted since financial problems can also occur due to other causes then cancer. In addition, the use of a validated financial toxicity measure and the use of a standard definition of financial toxicity will probably lead to results that can be more easily compared between studies.
In clinical practice, healthcare professionals should screen for financial toxicity during the disease trajectory. If financial toxicity is detected, directing patients to financial resources and advocating with an insurance company on behalf of the patient are possible actions one could take. Also, financial toxicity should be discussed with patients after diagnosis and regularly thereafter because it can influence treatment adherence and thus treatment efficacy. This is especially relevant in countries without universal healthcare coverage like the USA. In addition, healthcare professionals should have attention for the value of certain treatments in relation to their costs, and they should be prepared to discuss these tradeoffs with patients. This also implies that healthcare professionals' should be informed on the OOP costs related to treatment. Finally, to decrease financial toxicity, patient should have basic knowledge on health insurance, potential costs of treatment, and available resources as well.
In conclusion, this review shows that financial toxicity is common after a cancer diagnosis but varies strongly between countries since it depends much upon the healthcare system. Researchers, healthcare professionals, health and safety officers in the work place, and patients themselves should all cooperate to tackle these complex issues.

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
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