Abstract
Background/Aim: Organ-sparing treatment is increasingly used for bladder cancer, particularly for patients with significant comorbidities or advanced age. The upcoming treatment can cause distress and sleep disturbances. This study investigated pre-radiotherapy sleep disturbances in these patients. Patients and Methods: Twenty-two patients with bladder cancer scheduled for local or loco-regional radiotherapy were retrospectively evaluated. Sixteen characteristics were analyzed for sleep disturbances including age, sex, performance score, comorbidities, previous malignancy, distress score, emotional problems, physical problems, treatment situation, treatment intent, current primary tumor and nodal stage, distant metastasis, treatment volume, concurrent chemotherapy, and Coronavirus Disease 2019 pandemic. Results: Eleven patients (50.0%) reported sleep disturbances that were significantly associated with distress scores ≥5 (p=0.035). Trends were found for age ≤75 years (p=0.183), ≥2 emotional problems (p=0.183), ≥5 physical problems (p=0.064), and distant metastasis (p=0.090). Conclusion: Half of the patients reported pre-radiotherapy sleep disturbances. Risk factors facilitate identification of patients requiring psychological support.
When compared to other solid malignancies, cancers of the urinary bladder are comparably rare (1). Radical cystectomy is considered the standard approach in many institutions but can be associated with major complications including perioperative death (2-4). Therefore, bladder-sparing treatment approaches including radio-chemotherapy or radiotherapy and transurethral resection have become more popular, particularly for patients with significant comorbidities, worse performance status or advanced age (5-8). However, also multimodal bladder-sparing treatment can be quite burdensome for the patients, which may cause significant emotional distress associated with sleep disturbances. Moreover, to be scheduled for radiation therapy may aggravate the distress due to the fear of radiation exposure and high-tech machines. This idea is supported by a study performed in patients with breast or prostate cancer treated with local or loco-regional radiotherapy (9). In that study, the more pronounce sleep disturbances were reported by the patients before or during the initial phase of their course of radiotherapy. However, to our knowledge, no data have been reported so far regarding pre-treatment sleep disturbances in patients with bladder cancer assigned to a multimodal bladder-sparing treatment approach. The present study aimed to provide data for this group of patients by evaluating the prevalence of sleep disturbances prior to a radio-chemotherapy course and potential risk factors for such sleep disturbances. These data will likely contribute to the identification of patients who need psycho-oncological support before the start of their radiochemotherapy treatment.
Patients and Methods
Twenty-two patients with bladder cancer scheduled for local or loco-regional radiochemotherapy were retrospectively evaluated for pre-treatment sleep disturbances. All patients completed the National Comprehensive Cancer Network (NCCN) Distress Thermometer (10, 11). The study was approved by the local Ethics Committee (University of Lübeck, reference 21-284).
Volumetric modulated arc radiotherapy was delivered to the bladder (plus margins) in 11 patients, and to the bladder and locoregional lymph nodes (plus margins) in the other eleven patients. Planned total doses ranged between 50.0 Gy and 64.8 Gy with daily fractions of 1.8 Gy or 2.0 Gy given on five consecutive days per week. Finally, two patients received 64.8 Gy, 11 patients 59.4 Gy, one patient 50.4 Gy, one patient 48.6 Gy, and one patient 43.2 Gy in 1.8 Gy-fractions. In addition, two patients received 45.0 Gy and one patient 50.0 Gy in 2.5-Gy fractions, one patient 54.0 Gy in 2.0-Gy fractions, and one patient a cumulative dose of 53.0 Gy using two subsequent simultaneous integrated boost (SIB) concepts. One patient scheduled for 59.4 Gy in 1.8 Gy-fractions refused treatment after the informed consent discussion. Concurrent chemotherapy was planned to include two courses of cisplatin (25 mg/m2/d1-5 or 20 mg/m2/d1-6). Finally, fifteen patients received chemotherapy, eight with cisplatin (switched to carboplatin or mitomycin C after one course due to toxicity in one patient each), two patients with carboplatin, two patients with mitomycin, two patients with paclitaxel, and one patient (who had synchronous gastric cancer) with capecitabine. One patient scheduled for radiochemotherapy refused treatment after the informed consent discussion.
Sixteen characteristics (summarized in Table I) were analyzed for associations with sleep disturbances before the start of irradiation including age (≤75 vs. ≥76 years); sex (female vs. male); Karnofsky performance score (≤80 vs. ≥90); Charlson comorbidity index (≤6 vs. ≥7); history of previous malignancy (no vs. yes); distress score (0-4 vs. ≥5); numbers of emotional (0-1 vs. ≥2) or physical (0-4 vs. ≥5) problems according to the NCCN Distress Thermometer (10, 11); treatment situation (primary situation vs. recurrence); treatment intent (curative vs. palliative); current primary tumor stage (Ta-1 vs. T2-4); current nodal stage (N0 vs. N+); distant metastasis (no vs. yes); treatment volume of irradiation (without vs. with loco-regional lymph nodes); concurrent chemotherapy (no vs. yes), and timely connection to the COVID-19 pandemic (before vs. during).
Characteristics evaluated for potential associations with sleep disturbances prior to irradiation.
Potential associations between sleep disturbances prior to irradiation and the 16 investigated characteristics were evaluated with the Fisher’s exact test. p-Values <0.05 were considered indicating statistical significance and p-values <0.20 a trend.
Results
Eleven patients reported sleep disturbances prior to planned radiochemotherapy, which represented a prevalence of 50.0%. The occurrence of sleep disturbances was significantly associated with distress scores ≥5 (p=0.035) (Table II). In addition, trends for associations with pre-radiotherapy sleep disturbances were found for age ≤75 years (p=0.183), ≥2 emotional problems (p=0.183), ≥5 physical problems (p=0.064), and distant metastasis (p=0.090) (Table II). In contrast to these characteristics, the COVID-19 pandemic was not significantly associated and showed no trend for an association with sleep disturbances (p>0.999).
Associations between characteristics and sleep disturbances prior to irradiation.
Discussion
Many patients with cancer of the urinary bladder receive local or loco-regional radiotherapy with or without concurrent chemotherapy as part of a bladder-preserving multimodal treatment (12-17). Anticipation of radiochemotherapy or radiotherapy can be associated with sleep disturbances as a consequence of emotional distress and fears. In a prospective study of 56 patients who underwent radiotherapy for early-stage breast or prostate cancer, the patients reported more pronounced sleep disturbances prior to the start and during the first part of their course of radiotherapy (9). Since bladder cancer is significantly less common than breast or prostate cancer, no study is available so far that investigated pre-treatment sleep disturbances in patients irradiated for bladder cancer (1). Only one randomized study was found that analyzed the effect of individualized psychological intervention on post-operative sleep quality in patients undergoing surgery for bladder cancer (18). However, the prevalence of sleep problems was not stated. In the present small study, the prevalence of sleep disorders prior to planned radiochemotherapy was 50.0%, which was higher than that prior to radiotherapy or radiochemotherapy for other malignancies such as gynecological cancers, prostate cancer, rectal cancer, lung cancer, and anal cancer (19-23).
The second aim of the present study was the determination of risk factors for pre-treatment sleep disturbances in order to facilitate the identification of patients who may require psychological support already before the start of treatment. In our study, the occurrence of sleep disturbances was significantly associated with higher distress scores. In addition, trends were found for younger age, greater numbers of emotional problems, greater numbers of physical problems, and presence of distant metastasis. Since this is the first study particularly focusing on sleep disturbances prior to radiochemotherapy or radiotherapy for bladder cancer, our results cannot be directly compared to other studies.
However, when considering the results of previous studies investigating risk factors for sleep disturbances prior to radiotherapy in patients with other pelvic malignancies, some consistency can be observed (19-21). In a previous study of 62 patients with gynecological cancers, pre-radiotherapy sleep disturbances were significantly associated with greater numbers of physical problems, and a trend was found for greater numbers of emotional problems (19). Moreover, in a study of 42 patients with rectal or anal cancers, pre-radiotherapy sleep disturbances showed significant associations with higher distress scores and with greater numbers of physical problems or emotional problems (20). In a study of 48 patients scheduled for radiotherapy of prostate cancer, higher distress scores and greater numbers of physical problems were significantly associated with pre-radiotherapy sleep disturbances (21). Moreover, higher distress scores and greater numbers of emotional or physical problems were previously shown in patients irradiated for lung cancer and breast cancer (23, 24). Younger age did not prove to be a significant risk factor for pre-treatment sleep disturbances in patients with pelvic malignancies (19-21) but was significantly associated with the occurrence of pre-radiotherapy sleep disturbances in previous studies investigating patients irradiated for breast cancer (24) or head-and-neck cancers (25). In addition to these previously identified risk factors for sleep disturbances prior to a planned course of radiotherapy, presence of distant metastasis showed a trend in the present study. This finding can be explained by the fact that presence of metastasis represents a very advanced stage of a malignant disease, often associated with poor prognoses. Therefore, these patients likely experience a higher degree of emotional burden, which can lead to sleep disturbances. Despite the consistency with some results of previous studies, limitations of the present study, namely the retrospective nature and limited sample size, must be considered when interpreting its findings.
In summary, half of the patients reported pre-treatment sleep disturbances, which demonstrates the importance of this symptom. The risk factors for pre-treatment sleep disturbances found in this study can facilitate the identification of patients who require psychological support at an early stage, i.e., prior to the start of their course of radiochemotherapy or radiotherapy.
Acknowledgements
As part of the project NorDigHealth, this study was funded by the European Regional Development Fund through the Interreg Deutschland-Danmark program.
Footnotes
Authors’ Contributions
D.R., S.K., S.E.S., T.W.K., S.T. and T.B. participated in the design of the study. D.R. and S.K. provided the data that were analyzed by D.R. The article was drafted by D.R. and S.E.S; it was reviewed and approved by all Authors.
Conflicts of Interest
On behalf of all Authors, the corresponding Author states that there are no conflicts of interest related to this study.
- Received June 30, 2022.
- Revision received July 23, 2022.
- Accepted July 25, 2022.
- Copyright © 2022 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
