Abstract
Background/Aim: Upcoming radiotherapy for prostate cancer may lead to emotional distress. This study aimed to identify the prevalence and risk factors in a retrospective cohort of 102 patients. Patients and Methods: Thirteen characteristics were evaluated for six emotional problems. To account for multiple comparisons, Bonferroni correction was used; p-values <0.0038 were significant (alpha level <0.05). Results: Prevalence of worry, fears, sadness, depression, nervousness, and loss of interest in usual activities was 25%, 27%, 11%, 11%, 18%, and 5%, respectively. A greater number of physical problems was significantly associated with worry (p=0.0037) and fears (p<0.0001) and showed trends regarding sadness (p=0.011) and depression (p=0.011). Trends were also found for associations between younger age and worry (p=0.021), advanced primary tumor stage and fears (p=0.025), patient’s history of another malignancy and nervousness (p=0.035), and between external-beam radiotherapy alone and fears (p=0.042) or nervousness (p=0.037). Conclusion: Although the prevalence of emotional distress was comparably low, patients with risk factors may benefit from early psychological support.
Prostate cancer is the most common type of non-skin cancer among men in the United States and Europe, and the fourth most frequently diagnosed cancer worldwide (1). Many of these patients receive radiation therapy, either in the form of external-beam radiotherapy (EBRT) alone, brachytherapy alone, or a combination of both (2). In case of high risk or lymph node positive disease, radiotherapy often includes the elective pelvic lymph nodes. Prostate radiotherapy can be associated with significant acute and late toxicities and emotional distress (3-6). It is clinically relevant to identify patients who are at risk of experiencing emotional distress prior to or during prostate radiotherapy. These patients may benefit from early psychological support to guide them through the course of treatment. In this study, the prevalence of emotional distress and potential risk factors were evaluated in prostate cancer patients assigned to EBRT with or without a high-dose rate (HDR) brachytherapy boost.
Patients and Methods
One-hundred-and-two patients who received local or loco-regional radiotherapy for prostate cancer were retrospectively reviewed for six emotional problems including worry, fears, sadness, depression, nervousness, and loss of interest in usual activities (7). Each emotional problem was categorized as present or absent. The study achieved approval from the Ethics Committee at the University of Lübeck (2022-412). The patients had completed the National Comprehensive Cancer Network Distress Thermometer during the consent discussion regarding the planned radiotherapy (7).
Radiotherapy consisted of EBRT alone (n=76) or EBRT plus an HDR brachytherapy boost (n=26). Eleven of these 76 patients were scheduled for additional irradiation of loco-regional lymph nodes or pelvic lesions. Patients treated with EBRT alone were planned to receive total doses of 74-80 Gy (5×2 Gy per week) for definitive and 64-72 Gy (5×2 Gy per week) for adjuvant treatment, depending on tumor stage. Patients suitable for and agreeing to a brachytherapy boost were scheduled for 50 Gy of EBRT (5×2 Gy per week) plus two weekly fractions of 15 Gy of HDR brachytherapy. Prior EBRT, 50 patients had already received hormonal treatment, mainly with bicalutamide and/or leuprorelin-acetate.
For each of the six emotional problems stated above, 13 patient- and tumor-related characteristics were evaluated for potential associations. These characteristics included the relation to the COVID-19 pandemic (before vs. during), number of physical problems indicated by the patients when completing the distress thermometer (0-1 vs. ≥2), age at the start of EBRT (≤71 vs. ≥72 years, median=71 years), Karnofsky performance score (KPS ≤90 vs. 100), primary tumor stage represented by T-category (1-2 vs. 3-4), Gleason score (≤7 vs. 8-9), pre-radiotherapy prostate-specific antigen (PSA) level (<10 vs. ≥10 ng/ml), surgery (prostatectomy) prior to radiotherapy (no vs. yes), hormone therapy prior to radiotherapy (no vs. yes), brachytherapy boost in addition to EBRT (no vs. yes), treatment volume (without lymph nodes/pelvic lesions vs. with lymph nodes/pelvic lesions), patient’s own history of another malignancy (no vs. yes), and family history of malignancy (no vs. yes).
Potential associations between these characteristics and the six emotional problems were analyzed using the Chi-square test or, if the number of patients in a subgroup was <5, the Fisher’s exact test. Separate analyses were performed for each emotional problem. To account for multiple comparisons, the Bonferroni correction was used. p-Values <0.0038 were considered significant and represented an alpha level <0.05. In addition, p-values <0.05 were considered indicating a trend.
Results
The prevalence of the six emotional problems, namely worry, fears, sadness, depression, nervousness, and loss of interest in usual activities, was 25%, 27%, 11%, 11%, 18%, and 5%, respectively. A number of physical problems ≥2 was significantly associated with worry (p=0.0037) and fears (p<0.0001) and showed trends for associations with sadness (p=0.011) and depression (p=0.011). Moreover, trends were found for associations between age ≤71 years and worry (p=0.021), between tumor stage T3-4 and fears (p=0.025), between patient’s own history of another malignancy and nervousness (p=0.035), and between EBRT alone (i.e., without a brachytherapy boost) and fears (p=0.042) or nervousness (p=0.037). The complete results regarding the six emotional problems are summarized in Table I, Table II, Table III, Table IV, Table V, and Table VI.
Associations of the investigated characteristics and worry.
Associations of the investigated characteristics and fears.
Associations of the investigated characteristics and sadness.
Associations of the investigated characteristics and depression.
Associations of the investigated characteristics and nervousness.
Associations of the investigated characteristics and loss of interest in usual activities.
Discussion
Radiotherapy of prostate cancer can be associated with significant genitourinary and gastro-intestinal toxicity. In patients scheduled for radiotherapy, the risk of experiencing such complications may lead to emotional distress, which can be assessed with the National Comprehensive Cancer Network Distress Thermometer (7). This instrument includes six emotional problems, namely worry, fears, sadness, depression, nervousness, and loss of interest in usual activities. In the present study, the prevalence of these problems ranged between 5% and 27%. These rates are similar to those found in other settings of patients with prostate cancer. In a retrospective study of 861 men who received EBRT, brachytherapy, or radical prostatectomy during the last seven years, the prevalence of anxiety and depression was 25% and 17%, respectively (8). In another study that investigated the value of the distress thermometer to predict global distress in prostate cancer patients, less than 20% of the patients reported scores of ≥4, the cut-off score for significant distress (9). Moreover, pre-treatment sleep disorders, which can be a consequence of emotional distress, were previously reported in 21% of patients assigned to local or loco-regional radiotherapy for prostate cancer (10). The prevalence of emotional distress in the present study was lower than that in a previous study of breast cancer patients, where frequencies ranged between 15% and 46% for the six emotional problems (11). These findings were supported by the study of Stapleton et al., where the average distress of prostate cancer patients was significantly lower compared to breast cancer patients (12).
In our study, the prevalence of worry and fears was significantly associated with a greater number of physical problems including genitourinary and gastrointestinal disorders. In addition, the number of physical problems showed trends for associations with sadness and depression. These results are consistent with those of previous studies in other settings of prostate cancer. In a study using the data of 1,148 prostate cancer patients from a previous prospective study who had received surgery (63%) or radiation therapy (37%), patients with more impaired urinary, bowel, and sexual function reported greater emotional distress at different time points (13). In a study that analyzed the baseline data of a randomized trial including different treatments for prostate cancer, problems related to physical and daily living were significantly associated with global distress (p<0.0005) (9). In a prospective non-randomized study comparing different types of primary treatment for prostate cancer, psychological distress, depression, and anxiety were associated with urinary disorders and worsening of sexual function (14). Moreover, in a retrospective study of 253 patients treated with radical prostatectomy and 87 patients receiving EBRT for localized prostate cancer, patients tending to experience moderate to high distress had worse urinary or gastro-intestinal disorders (15). The results from previous studies were further supported by a review article considering 18 original and other review articles (16).
In addition to the impact of the number of physical problems on the development of emotional distress, the present study revealed trends for younger age, higher T-category, patient’s history of another malignancy, and treatment with EBRT alone (without an HDR brachytherapy boost). Younger age was previously identified as risk factor for anxiety in long-term survivors after radical prostatectomy (17). Moreover, in the study of Lotfi-Jam et al. distressed patients were non-significantly younger than non-distressed patients (9). Mean age was 66.6 vs. 67.7 years (p=0.24), and 61.5% vs. 68.7% of the patients were 65 years or older (9). A higher T-category represents a more advanced tumor stage associated with a higher risk of a recurrence of prostate cancer. The fact that the fear of a recurrence is a significant burden for prostate cancer patients requiring psychosocial care has been described in several studies (18-20). Moreover, an advanced tumor stage requires higher doses of radiotherapy associated with an increased risk of acute and late toxicity, which likely results in higher levels of emotional distress. An association between advanced tumor stage and emotional distress prior to a course of radiotherapy was found also in a previous study of breast cancer patients (11). Similar to the fear of a recurrence, a history of another malignancy may contribute to the level of emotional distress. In the previous study of breast cancer patients, a trend was found between a positive own or family history of breast cancer or ductal carcinoma in situ and the prevalence of emotional problems (11). Another result of the present study was a trend between EBRT without an HDR brachytherapy boost and a higher prevalence of emotional problems. This finding may be explained by the fact that HDR brachytherapy is safe and associated with less toxicity than EBRT alone (3, 21). For example, in the study of Noda et al. no patient experienced grade ≥2 genitourinary toxicity, and no patient developed grade 3 late gastro-intestinal toxicity after EBRT plus an HDR brachytherapy boost (21). However, although the results of the present study agree with those of previous studies or, if novel, can be sufficiently explained, the retrospective design and the risk of a hidden selection bias need to be considered when interpreting the results.
In summary, the prevalence of six relevant emotional problems was determined, which was lower than that in previous studies of breast cancer patients. Despite the comparably low prevalence, a considerable number of prostate cancer patients have risk factors of emotional distress. In the present study, a greater number of physical problems, younger, advanced primary tumor stage, patient’s history of another malignancy, and EBRT alone were identified as risk factors of emotional distress. Patients with these risk factors may benefit from early psychological support.
Footnotes
Authors’ Contributions
All Authors participated in the design of the study. A. A.-S. and D.R. provided the data that were analyzed by D.R. The article was drafted, reviewed and finally 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 February 17, 2023.
- Revision received February 28, 2023.
- Accepted March 1, 2023.
- Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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).
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