Effects of anxiety, depression, and fatigue on quality of life in early esophageal cancer patients following endoscopic submucosal dissection

Introduction

Esophageal cancer (EC) is among the most prevalent cancers of the upper digestive tract and was reported as the sixth most common cause of death due to malignant tumors worldwide (1). In China, EC has the sixth highest incidence rate among cancers, affecting an estimated 17.87 per 100,000 people, and a mortality rate of 13.68 per 100,000 people (2). EC has a poor prognosis, with a five-year survival rate of 20% (at most) (3). Surgical intervention can provide a relatively satisfying prognosis for patients with early or middle stage EC. However, esophagectomy for EC is often associated with a high incidence of complications that worsen the prognosis of patients (4).

The development of endoscopic submucosal dissection (ESD), which is now considered an acceptable treatment for early EC, has several advantages compared to esophagectomy including preservation of esophageal function, minimal invasiveness, less complications, lower cost, and shorter hospital stay (5). In addition, quality of life (QoL) following ESD is also considered as an important outcome for EC patients. Several studies have demonstrated that ESD provided a better postoperative QoL than surgery for early gastric and colorectal cancer patients (6,7). However, many EC patients may suffer from physical and psychosocial problems due to cancer symptoms and side effects of treatment, which may dramatically impact their QoL. Previous studies have mainly focused on the effects of physical problems on QoL in EC patients (8,9). Minimal attention has been given to the repercussions of emotional problems on the QoL of EC patients. Baudry et al. revealed that reducing the emotional distress of EC patients could improve their QoL either in the pre- or postoperative stage (10).

Patients enrolled in this study received surgical treatment. To our knowledge, there are no related studies investigating the effects of emotional factors on QoL in early EC patients. Hence, the present study was conducted to preliminarily investigate the QoL of early EC patients following ESD treatment and determine the effects of anxiety, depression, and fatigue on QoL. We present the following article in accordance with the STROBE reporting checklist (available at http://dx.doi.org/10.21037/apm-20-1632).

Methods

Patient selection

This was a prospective observational study to assess the QoL of early EC patients. Early EC patients admitted to the People’s Hospital of Rugao from December 2017 to January 2019 were enrolled in this study. Patients eligible for inclusion were older than 18 years of age, diagnosed as early EC (cT1aN0M0 or cT1bN0M0) by biopsy or imaging test, had no contraindications of ESD, received no previous surgical resection treatment and signed the written informed consent. Patients who refused to participate in the study or sign the written informed consent were excluded. The study was performed in compliance with the ethical principles outlined in the World Medical Association’s Declaration of Helsinki (as revised in 2103) and was approved by the ethics committee of the People’s Hospital of Rugao (No. 00201714).

Data collection

Demographic and clinical characteristics of patients were recorded following enrollment in the study. Recorded data included age, gender, education, marital status, employment status, capacity to pay for treatment, number of comorbidities, tumor stage, tumor location, tumor size, circumferential range, complete resection rate, and complications of ESD. All ESD procedures in this study were performed by skilled operators, in order to minimize the impacts of different operators on patients.

Assessment of QoL

QoL was assessed according to the European Organization for Research and Treatment of Cancer QoL (EORTC QLQ-C30) (11) within 3–6 months after the patients were discharged from hospital. EORTC QLQ-C30 is a self-report scale specifically designed for cancer patients, and includes 30 items that can be divided into five functional scales (physical function, role function, emotional function, cognitive function, and social function) and one global health status scale. The total score in each scale ranges from 0 to 100, with a higher score indicating better QoL of patients. In this study, a total score of 75 was set as a cut-off; so a score <75 represented a poor QoL, while a score >75 represented a satisfying QoL.

Assessment of anxiety, depression, and fatigue

The Beck Anxiety Scale (BAS) was used to measure the severity of anxiety symptoms in enrolled patients (12). The BAS is a self-report scale and generally consists of 21 items, with each item being scored from 0 to 3. Therefore, the total score of each patient ranges from 0 to 63 scores. In this case, a higher total score indicates more severe anxiety symptoms in patients. Our study defined anxiety symptoms as minimal if the total score was between 0 and 7, mild if between 8 and 15, moderate if between 16 and 25, and as severe if between 26 and 63.

The Beck Depression Scale (BDS) was then employed to assess the intensity of depression (13). Similar to the BAS, the BDS also contains 21 items, with each item being scored from 0 to 3 to obtain a total score ranging from 0 to 63. A total score of 0–9 indicated minimal depression, 10–18 indicated mild depression, 19–29 indicated moderate depression, and 30–63 indicated severe depression.

Fatigue was assessed according to the symptom subscale of the EORTC QLQ-C30. There were three items regarding physical strength in the symptom subscale, and each item could be scored from 0 to 3 scores. The total score of the three items were then transformed on a 0–100 scale. In this study, a total score of >75 represented a poor condition of physical strength.

Statistical analysis

Statistical analyses were performed using SPSS (version 22.0, SPSS Inc., Chicago, IL, USA). Categorical variables were reported as numbers and percentages, and continuous variables were reported as means ± standard deviations. Univariable and multivariable logistic regression models were constructed to determine the causes of three emotional problems, namely anxiety, depression, and fatigue. Furthermore, a linear regression model was employed to explore the impacts of the aforementioned emotional difficulties on the QoL of early EC patients undergoing ESD. Some demographic and clinical characteristics of patients were adjusted in both multivariable regression models to reduce the bias of these data on the results. For all analyses, a P value <0.05 was considered statistically significant.

Results

In total, there were 92 early EC patients admitted to the hospital from December 2017 to January 2019. Of this initial cohort, 13 patients refused to participate in this study. ESD procedures were uncompleted in three patients due to severe bleeding, and in one patient due to fibrosis. Finally, 75 early EC patients were enrolled in this study (as shown in Figure 1). Demographic and clinical characteristics of enrolled patients are summarized in Table 1. The majority of patients were elderly, with the 60–70 years old cohort accounting for 48% of all included patients. There were 41 male and 34 female patients. Most patients were not well educated and only 12 patients had attended high school or above. Approximately 75% of the patients had a partner and 32 patients were employed at the time. Most importantly, roughly one third of patients had insufficient financial capacity to pay for treatment, and half of the patients suffered from at least two comorbidities.

Figure 1 Flow chart showing the process of patient selection.

Table 1 Demographic and clinical characteristics of enrolled patients (n=75)
Full table

In terms of cancer characteristics, only early EC patients were enrolled in this study. Of the 75 included patients, 53 were diagnosed as T1aN0M0 and 22 as T1bN0M0. Most tumors (73.3%) were located in the middle of the esophagus. The tumor size was small (<20 mm) in 49 patients and relatively large (≥20 mm) in the remaining 26 patients. Tumors had invaded more than half of the circumference of the esophagus in 63 patients. 74 patients received a complete resection.

Emotional problems including anxiety, depression, and fatigue were assessed in all enrolled patients (Table 2). In general, 32 patients had symptoms of minimal anxiety, 21 patients had symptoms of mild anxiety, 15 patients had symptoms of moderate anxiety, and seven patients had symptoms of severe anxiety. With regards to depression, 39 patients had symptoms of minimal depression, 15 patients had symptoms of mild depression, 19 patients had symptoms of moderate depression, and two patients had symptoms of severe depression. Furthermore, 27 patients frequently felt fatigued.

Table 2 Prevalence of emotional problems in enrolled EC patients (n=75)
Full table

The causes of emotional distress in patients were analyzed using univariable and multivariable logistic regression models (as shown in Table 3). The multivariable logistic regression model revealed that older (≥60 years) or female patients were more likely to suffer from moderate or severe anxiety than younger or male patients (P=0.045 and 0.048, respectively). The financial capacity to pay for treatment had a significant impact on the triggering of anxiety symptoms in the enrolled patients (P<0.001). Similarly, age, gender, and capacity to pay also played key roles in depression symptoms. Moreover, higher education level and smaller tumor size may be able to relieve symptoms of depression to some extent (P=0.048 and 0.018, respectively). Fatigue was found to be related only to age and gender.

Table 3 Demographic and clinical characteristics were associated with emotional problems in early EC patients according to the logistic regression model
Full table

The QoL of early EC patients was then assessed according to EORTC QLQ-C30. The mean scores of five functional scales and one global health status scale are summarized in Table 4. The mean scores in enrolled patients were as follows: physical function was 88.1±12.9, role function was 85.5±16.8, emotional function was 77.9±12.5, cognitive function was 93.4±14.7, and social function was 91.0±17.2. The mean score of global health status was 76.9±15.2. Risk factors for reduced QoL were estimated according to univariable and multivariable linear regression models (shown in Table 5). Anxiety, depression, fatigue, age, gender, capacity to pay, and number of comorbidities were initially found to be significantly associated with QoL based on the results of the univariable linear regression analysis. However, after adjusting for confounding factors using a multivariable linear regression model, moderate or severe symptoms of anxiety, depression, and fatigue, older age, and insufficient capacity to pay for treatment were identified as independent risk factors for reduced QoL.

Table 4 Summary of EORTC QLQ-C30 in enrolled EC patients
Full table

Table 5 Univariable and multivariable linear regression model estimating independent risk factors for reduced QoL in early EC patients
Full table

Discussion

To our knowledge, this is the first study to investigate the effects of anxiety, depression, and fatigue on QoL in early EC patients receiving ESD treatment. This study enrolled 75 patients from December 2017 to January 2019, and demonstrated that some demographic characteristics of patients including capacity to pay for treatment, age, gender, education status, and tumor size may cause emotional distress. Additionally, the prevalence of emotional problems, such as anxiety, depression, and fatigue may reduce the QoL of early EC patients following ESD treatment.

The prevalence of anxiety (57.3%) and depression (48.0%) among the enrolled patients in the study were similar to previous studies involving cancer patients (10,14). We further investigated the causes of emotional problems. Several previous studies have reported that age and gender may be associated with the incidence of emotional distress in cancer patients (15,16). Mols et al. reported that older and male colorectal cancer patients had considerably fewer symptoms of anxiety, yet exhibited more symptoms of depression (15). Moreover, Weiss Wiesel et al. found that anxiety decreased with age in older cancer patients receiving chemotherapy, while depression remained constant with age (17). However, our study found that the severity of both anxiety and depression symptoms decreased in older and male patients, which might be explained by cultural differences between diverse countries. In addition, early EC posed a relatively low psychological burden on patients compared with colorectal cancer.

It is understandable that an inability to pay the cost of treatment acted as a key cause of emotional distress. Several studies have also highlighted the important role of financial difficulties in the development of emotional problems in cancer patients (18,19). Thus, measurements in the present study were taken to ensure that the rate of underdiagnosed psychiatric morbidities was reduced, especially for patients that are financially-burdened.

The most important finding of our study was the independent risk factors for reduced QoL in early EC patients. Depression was the major risk factor impacting QoL, especially functional status. Previous studies have shown that patients with depression typically experience a worse QoL compared with patients that do not suffer from depression (20,21). Our study obtained a similar result, indicating that the prevalence of depression significantly reduced the QoL score in early EC patients. Furthermore, we found that anxiety played a similar role to depression. The QoL of lung cancer patients was reported to be associated with both anxiety and depression (22). Bellali et al. proposed that early assessment of anxiety and depression may provide information and insight regarding vulnerable patients and guide the implementation of targeted treatment strategies (23). Fatigue is a common symptom in cancer patients and accounted for 36.0% in our study. Also, it itself was part of scale for assessing QoL. It has been shown that fatigue is associated with the presence of inflammation, as well as poor quality of sleep and QoL in patients with advanced cancer (24). The combination of multiple factors can induce fatigue in cancer patients. Our study demonstrated that fatigue was only related to age and gender considering the relatively low burden of cancer in the enrolled early EC patients.

Interestingly, the characteristics of the tumor had no significant relation to either emotional problems or QoL in early EC patients. In practice, most early EC patients do not require further chemotherapy after ESD treatment, and thus, ESD does not significantly increase the burden on patients. So, the reduced QoL in patients primarily resulted from emotional distress and financial difficulties.

Some limitations of this study should be noted. Firstly, only 75 early EC patients were enrolled in the study. This small sample size, coupled with the short study duration and single center study design hindered further analysis. Secondly, the majority of patients enrolled in this study were not well educated, which made it difficult to analyze the impact of education status on emotional problems and QoL. Thirdly, the incidence of esophageal stenosis after ESD may also be the main factor affecting the recovery and quality of life of patients. However, we didn’t record the degree of stenosis in enrolled patients during the period of follow up.

In conclusion, ESD is considered an acceptable treatment for early EC and can provide better QoL outcomes than surgical procedures. Our prospective study verified the incidence of anxiety, depression, and fatigue in early EC patients following ESD treatment, which could reduce the QoL of EC patients. This finding emphasizes the importance of psychosocial health in patients receiving ESD treatment and highlights the need to strengthen psychological counseling in clinical practice.

Acknowledgments

Funding: This work was supported by the National Natural Science Foundation of China (81700575).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at http://dx.doi.org/10.21037/apm-20-1632

Data Sharing Statement: Available at http://dx.doi.org/10.21037/apm-20-1632

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/apm-20-1632). The 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. The study was performed in compliance with the ethical principles outlined in the World Medical Association’s Declaration of Helsinki (as revised in 2013) and was approved by the ethics committee of the People’s Hospital of Rugao (No. 00201714). Informed consent was taken from all the patients.

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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(English Language Editor: A. Kassem)