The Impact of Depression and Anxiety on Adult Cancer Patients’ Health-Related Quality of Life

Background: Cancer patients are at high risk for mental illness and, in turn, poorer health-related quality of life. This study used nationally representative United States (US) data to examine nuances of the impact of depression and/or anxiety on HRQoL in different cancer groups (e.g., cancer only, cancer and depression, cancer and anxiety, cancer and both conditions). Methods: Adult patients aged 18 years and older with a cancer diagnosis were identified from the Medical Expenditure Panel Survey data for 2012–2016. HRQoL was measured using the SF-12 Physical and Mental Component Summary (PCS & MCS) scores. Multivariate linear regressions were used, controlling for a multitude of factors. Results: Around 12% of the 1712 identified patients with cancer had depression, 13% had anxiety, and 8.4% had both depression and anxiety. Patients with comorbid depression and anxiety had the lowest mean scores of both PCS and MCS compared to patients in other groups. In addition, cancer patients with either depression and/or anxiety were more likely to have lower MCS scores compared to those with cancer only (depression: β = −6.554; anxiety: β = −3.916; both conditions: β = −11.759, p < 0.001). Interestingly, patients with comorbid depression and anxiety were more likely to have higher PCS scores compared to those with cancer only. Conclusions: The psychological burden of cancer is immense, with a substantial impact on patients’ HRQoL. Routine screening for depression and anxiety, especially for women and those with low poverty status and comorbidities, should be conducted by healthcare providers to identify those with high odds of having a lower HRQoL. Additionally, early psychiatric interventions, such as psychotherapy and prescription drugs, may positively impact patients’ mental well-being and HRQoL.


Introduction
Cancer is one of the leading causes of morbidity and mortality worldwide [1]. Early diagnosis and treatment of cancer have resulted in higher survival rates for most types of cancer [2]. In the United States (US), the most common types of newly diagnosed cancer cases in 2019 for women were breast cancer (30%), followed by lung and bronchus cancer (13%). For men, prostate cancer was the most commonly reported type (20%), followed by lung and bronchus cancer (13%) [2]. Cancer diagnosis and treatment are associated with a significant negative psychological impact leading, in many cases, to depression and anxiety. It has been estimated that 8-25% of patients with cancer have depression, and 17% have anxiety [3,4]. However, depression and anxiety are often under-diagnosed and under-treated among cancer patients due to overlapping symptoms with cancer-related fatigue and pain [5].
Undiagnosed and untreated anxiety and depression in patients with cancer can worsen health outcomes and potentially increase cancer-related morbidity and mortality [6,7]. For instance, depression and anxiety among patients with cancer are associated with higher healthcare costs and utilization [8][9][10] and lower adherence to cancer treatment [11,12]. A retrospective analysis of administrative data of 5055 patients with cancer in the US reported that patients with depression have significantly more annual non-mental-health provider healthcare visits, emergency department visits, and hospital readmissions compared to cancer patients without depression [9]. Moreover, depression and anxiety among patients with cancer are also associated with poor health-related quality of life (HRQoL) [13,14]. Among the different domains of HRQoL, the mental and physical domains are believed to be predominately impacted by illnesses such as cancer [15]. Poor HRQoL can negatively affect cancer survival rates. For example, in a cohort of older women with breast cancer, patients' HRQoL scores were significantly associated with their 10-year risk of mortality [16]. In a cohort of colorectal cancer, patients' HRQoL, depression, and anxiety scores increased the risk of dying the following year by 22%, 7.2%, and 12%, respectively [17].
Multiple studies have investigated the impact of depression and/or anxiety on HRQoL among patients with breast [18], colorectal [19], lung [20], thyroid [21], and head and neck cancer [22]. These studies suggested that both depression and anxiety are related to worse HRQoL. While these studies contributed to the body of knowledge about the impact of depression and/or anxiety on HRQoL among adults with cancer, none of them compared the impact of depression and/or anxiety on HRQoL using national US data across different groups of cancer patients (e.g., cancer only, cancer and depression, cancer and anxiety, cancer and both conditions). Furthermore, socioeconomic factors, access to care, physical activity, smoking, and medical comorbidities are believed to affect the HRQoL of adults with cancer [15]. Therefore, this study aimed to examine the impact of depression and/or anxiety on HRQoL among different groups of cancer patients (i.e., cancer only, cancer and depression, cancer and anxiety, cancer and both conditions) using nationally representative US data and controlling for a multitude of potential confounders that could impact the HRQoL for adults with cancer. Due to the high rates of comorbid depression and anxiety in patients with cancer, it is crucial to evaluate how these mental health conditions contribute to their health-related quality of life.

Study Design and Data
A cross-sectional study was conducted using the Medical Expenditure Panel Survey (MEPS) data. Three alternate years of data (2012, 2014, and 2016) were used based on the recommendations of MEPS to avoid duplicate observations of the same participant (as a result of longitudinal follow-up of MEPS), and multiple years of data were pooled to increase the sample size. The Agency for Healthcare Research and Quality (AHRQ), which is responsible for the MEPS database, makes MEPS data publicly available online for researchers, and data are anonymous. The MEPS is a nationally representative survey of the noninstitutionalized US civilian population with ages ranging from 18 to 64 years old. The MEPS provides information on sociodemographic factors, health insurance, health conditions, medication use, and other health services.

Study Population
Adults aged 18-64 years diagnosed with cancer using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) clinical diagnoses codes and who were alive during the calendar years were included in the study. The study included adult patients with all types of cancer, such as breast, prostate, colon, rectum, lung, pancreas, lymphomas, etc. The MEPS assessed HRQoL using the Short-Form 12 Version 2 (SF-12V2); physical and mental domains of HRQoL were assessed using the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the questionnaire [23]. The PCS and MCS were included in the analysis as continuous variables, with higher scores representing better physical and mental HRQoL, respectively.

Independent Variables
The key independent variable was cancer group; adults with cancer were categorized into four mutually exclusive cancer groups (e.g., cancer only, cancer and anxiety, cancer and depression, or cancer and both conditions). In addition, this study identified individuals with depression and anxiety from the MEPS file using the clinical classification codes (651 for anxiety, 657 for depression) and the ICD-9-CM codes of 296, 300, and 311 for depression. These conditions were first reported by households, recorded by qualified coders, and then converted into clinical classification codes by MEPS researchers. Other independent variables included sociodemographic characteristics (i.e., gender, age in years, race/ethnicity, marital status, region of residence, education level), employment status, poverty status, health insurance (public, private, and uninsured), and medication insurance. Poverty status was defined using family income relative to the federal poverty line (FPL) and classified as poor (<100% FPL), near poor (100% to <200% FPL), middle income (200% to <400% FPL), and high income (≥400% FPL). Physical activity level, smoking status, perceived physical health, and comorbid chronic health conditions were also included as potential confounders. For the purpose of this study, comorbidity refers to one or more other health conditions among persons with an index disease (e.g., cancer) [24].

Statistical Analyses
Descriptive statistics were conducted to describe the study population. Chi-square tests were used to identify the differences in the level of depression or anxiety or both in each independent variable category. Mean differences in HRQoL by cancer group were identified using ANOVA. Multivariable linear regressions were used to examine the association between cancer groups and HRQoL after adjusting in the regression model for age, gender, race/ethnicity, marital status, region of residence, education level, employment status, poverty, health insurance, medication insurance, physical activity, smoking, perceived physical health, and comorbid chronic health conditions. All estimates in the statistical analyses integrated MEPS person-level weights and variance adjustment weights (strata and primary sampling unit) that permit estimates to be nationally representative and account for the MEPS's complex survey design. SAS 9.4 (SAS Institute Inc., Cary, NC, USA) was used to analyze the data. A p-value of less than 0.05 was considered statistically significant.

Cancer Groups and Health-Related Quality of Life
There was a significant difference in HRQoL (PCS and MCS scores) among cancer groups ( Table 2). For example, the lowest mean PCS was observed in cancer patients with both depression and anxiety (mean = 37.9, SE = 1.30) compared to other groups (44.8 for cancer and depression, 48.2 for cancer and anxiety, and 53.2 for cancer only).  Table 3 displays the adjusted relationship among cancer groups and HRQoL. A significantly lower HRQoL was found in cancer patients with depression (MCS: β = −6.554, p < 0.001), anxiety (MCS: β = −3.916, p < 0.001), and both depression and anxiety (MCS: β = −11.759, p < 0.001) compared to those with cancer only after adjusting for age, gender, race, marital status, education level, employment status, poverty, insurance, and comorbidities.

Discussion
This study examined the impact of depression and anxiety on HRQoL among adults with cancer. The study found that about 12% of patients with cancer had depression, 13% had anxiety, and 8.4% had both depression and anxiety. The prevalence rates of both depression and anxiety are similar to the published rates reported in the existing literature and were associated with poor quality of life [3,4].
Our study found a higher rate of depression among women compared to men, unemployed cancer patients compared to employed patients, and patients with comorbidities compared to those without comorbidities. Therefore, special attention should be paid to patients with multiple comorbidities, patients who are unemployed, and female patients to detect early signs of depression and/or anxiety and manage them accordingly.
The HRQoL was measured and compared among four cancer groups (i.e., cancer only, cancer and depression, cancer and anxiety, and cancer and both conditions). The current findings show that neither anxiety nor depression is associated with the physical health domain of HQRoL, and this is consistent with a study of patients with different types and stages of cancer [13]. The study findings also indicate that depression and anxiety are each associated with the mental health domain of HRQoL in patients with cancer. Comparisons of cancer groups suggested that cancer groups with no depression or anxiety had better HRQoL than those with depression only, anxiety only, or comorbid depression and anxiety. Additionally, patients with cancer and comorbid depression and anxiety had worse HRQoL in the mental health domain than cancer patients with either depression or anxiety or without these conditions. This finding indicates the additive effects on HRQoL for adults with cancer with comorbid depression and anxiety. Furthermore, Brown et al., in their study of 405 adult oncology patients, also showed that comorbid anxiety and depression have additive effects on the mental health domains of HRQoL [13].
Our study findings are in line with other internationalg findings from published studies of patients with breast [18], colorectal [19], lung [20], thyroid [21], and head and neck cancer [22]; however, this is the only study that used nationally representative data to evaluate the impact of depression and anxiety (separately and as comorbid conditions) on HRQoL. Previous studies used self-reported scales to measure depression and anxiety; however, this study used clinical diagnostic codes. We also adjusted for comprehensive factors that could affect the association between depression and/or anxiety and HRQoL.
These findings support the need for comprehensive cancer care that includes mental health care and the identification of patients who may benefit from early mental health treatment or social support. Studies have shown that one-third of patients with cancer and depression do not receive any treatment for depression [25,26]. Although anxiety and depression are very common among patients with cancer and have negative health consequences, they are manageable chronic conditions [27]. Therefore, early diagnosis and treatment of depression and anxiety can reduce cancer symptoms and side effects from treatment and improve HRQoL generally. Furthermore, social support has been found to be associated with improvements in anxiety and depression and HRQoL among patients with cancer [28]. This finding supports the need for comprehensive cancer care that includes mental health care and the identification of patients who may benefit from early mental health treatment or social support.

Study Strengths and Limitations
This is the first study that compared the HRQoL among four cancer groups (i.e., cancer only, cancer and depression, cancer and anxiety, and cancer and both conditions). This study used a reliable and valid assessment tool to evaluate the impact of depression and/or anxiety on the HRQoL of patients with cancer. Moreover, this study controlled for comprehensive factors such as sociodemographic characteristics, physical activity, smoking, health insurance coverage, and comorbid chronic health conditions. In addition, using a nationally representative sample of adults with cancer enabled us to obtain accurate estimates of the prevalence rates of depression and/or anxiety among cancer patients. However, the results of this study should be taken in the context of some limitations. Cancer-related factors that may impact the HRQoL, such as stage at cancer diagnosis, cancer treatment, pain, and fatigue symptoms, are unavailable in the MEPS and, therefore, were not adjusted in the analysis. Moreover, the severity of depression and anxiety that may affect the HRQoL of adults with cancer is not available in the MEPS and, hence, was not adjusted for in the regression analysis. Depression and anxiety may be under-recognized, and the prevalence rate of these mental conditions may have been underestimated. Additionally, it was difficult to evaluate the causal relationship due to this study's cross-sectional design. Finally, the study's findings cannot be generalized to the elderly (aged 65 years and older) as this study included adults only (18-64 years old).

Clinical Implications
Findings from this study suggest that routine screening for depression and anxiety, especially for women and those with poor poverty status and comorbidities, needs to be performed by oncologists and other healthcare providers to identify those with a depression and anxiety diagnosis and, therefore, high odds of having lower HRQoL andpoorer long-term outcomes. In addition, based on the Pan-Canadian and the American Society of Clinical Oncology (ASCO) guidelines, it is recommended that a periodic assessment of depression and anxiety symptoms be performed for all patients with cancer over the course of care [29]. Depression and anxiety may hinder the management of cancer [30]; therefore, healthcare providers should not delay treating depression and anxiety because early detection and treatment can improve HRQoL and other cancer-related health outcomes [31]. Finally, coordinated care between healthcare providers and the provision of patient-centered information are important elements of patient care and may also improve HRQoL and ameliorate anxiety and depression in patients with cancer [32].

Conclusions
The results of this study suggest that depression and anxiety are associated with lower HRQoL among patients with cancer. Underestimating the consequences of these psychological distresses may negatively affect cancer health outcomes. Therefore, early assessment and treatment of depression and anxiety by oncologists and other healthcare providers for patients with cancer-especially women, those with poor poverty status, and those with comorbidities-are recommended to alleviate anxiety and depression and, thereby, improve the HRQoL of patients with cancer and other cancer-related health outcomes. Institutional Review Board Statement: Ethical review and approval were waived for this study as this study used a secondary database, "the Medical Expenditure Panel Survey (MEPS) database", a publicly available database; as such, ethics approval was waived.
Informed Consent Statement: Patient consent was waived due to for this study as this study used a secondary database, "the Medical Expenditure Panel Survey (MEPS) database", a publicly available database; as such, consent to participate was waived.

Data Availability Statement:
The dataset used in this article is available from MEPS database and is openly made available for researchers at the following website: https://meps.ahrq.gov/data_stats/ download_data_files.jsp (accessed on 26 December 2021). The Agency for Healthcare Research and Quality makes MEPS data publicly available online for researchers, and data are anonymous.

Conflicts of Interest:
The author declares that there is no conflict of interest regarding the publication of this paper.

Abbreviations
HRQoL Health-Related Quality of Life US United States SF- 12 12-Item Short-Form Health Survey MCS Mental Health Component Score PCS Physical Health Component Score Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.