Abstract
Background/Aim: In patients irradiated for high-risk prostate cancer, bladder volumes should be ≥200 ml to reduce the risk of radiation cystitis. A prospective trial evaluates a reminder app to increase bladder filling during irradiation without pelvic lymph nodes (LN). This retrospective study investigates whether patients irradiated with LN can also be included in that trial.
Patients and Methods: Forty patients irradiated with (N=17, group A) or without (N=23, group B) pelvic LN and presenting with a pre-irradiation bladder volume <200 ml were analyzed regarding fractions with a bladder volume <200 ml.
Results: Mean numbers of fractions with a volume <200 ml in the entire cohort, group A, and group B were 29.0±7.0, 28.8±7.6, and 29.2±6.6, respectively. The difference between groups A and B was not significant (p=0.978).
Conclusion: Irradiation of pelvic LN had no significant impact on the number of fractions for bladder volumes <200 ml. Patients irradiated with LN may be included in the prospective trial.
Introduction
Many patients with high-risk prostate cancer receive conventionally fractionated definitive radiotherapy with doses per fraction of 2.0 Gy and total doses up to 80 Gy (1). This treatment is often associated with urinary discomfort caused by radiation cystitis. Previous studies have shown that the occurrence of cystitis is inversely correlated with bladder volume before or during the radiotherapy course (2-4). The risk of this treatment-related side effect was particularly increased if the bladder volume was less than 180 or 200 ml (2-4). Therefore, radiation oncologists should strive for a minimum bladder volume of 200 ml at the time of the planning computed tomography (CT-simulation) and as many treatment sessions (radiation fractions) as achievable. One idea to improve the bladder filling status is the implementation of drinking protocols (5-10). However, adhering to a drinking protocol often requires considerable discipline from patients. This has led to the development of a mobile application (reminder app). This app reminds the patients on each treatment day of drinking 300 ml of water 45 min prior to the start of their radiation session. The potential benefit of the reminder app is currently investigated in two phase 2 trials (11, 12). One of these trials focuses on high-risk patients treated with definitive irradiation to the prostate and the seminal vesicles (12). However, in many patients with high-risk prostate cancer, the treatment volume also includes pelvic lymph nodes (LN). The question has arisen whether these patients should be included in our trial as well. Therefore, the present retrospective study was performed in patients receiving conventionally fractionated radiotherapy for high-risk prostate cancer. It includes both patients irradiated at prostate and seminal vesicles alone and patients additionally irradiated at the pelvic LN. The study investigates the impact of the treatment volume (with vs. without pelvic LN) and seven other patient- and tumor-related characteristics on the number of radiation fractions with a bladder volume <200 ml. The outcomes of this study are mandatory for a planned amendment of our ongoing prospective trial (10).
Patients and Methods
Data of 40 patients irradiated for high-risk prostate cancer between 2021 and 2025 were retrospectively analyzed. In 17 of these patients, the treatment volume included the pelvic LN (group A), and 23 previously reported patients (group B) were irradiated without pelvic LN (13). The current version of this retrospective study was approved via an additional amendment by the leading Ethics Committee at the University of Lübeck under the file number 2024-447_4.
Inclusion criteria included histologically confirmed high-risk prostate cancer, treatment with external-beam radiotherapy with or without pelvic LN (no surgery, no brachytherapy), and a pre-treatment bladder volume <200 ml. To be rated as high-risk cancer, patients were required to have a prostate-specific antigen (PSA) level >20 ng/ml, and/or a Gleason score ≥8, and/or a primary tumor stage of T2c or higher (1). Due to the high-risk situation, all patients received antihormonal therapy before and/or during and/or following the course of radiotherapy. Total doses of conventionally fractionated (dose per fraction=2.0 Gy) irradiation ranged between 74 Gy and 80 Gy (median dose=78 Gy). Like in previous studies, statistical analyses considered the initial 35 fractions (treatment sessions) (13, 14). At each session, the volume of the urinary bladder was determined using the current cone-beam computed tomography. Of the resulting bladder volumes, the mean [plus/minus standard deviations (±SD)] and median [plus interquartile ranges (Q1-Q3)] numbers of treatment sessions with a bladder volume <200 ml were calculated. In addition, eight possible risk factors for inappropriate filling of the urinary bladder (<200 ml) during the radiotherapy course were evaluated. These factors included irradiation of pelvic LN, age, Karnofsky performance score, body-mass index, prostate volume prior to irradiation, pre-treatment PSA level, Gleason score, and stage of the primary tumor (Table I). As done in the previous studies, standard methods of descriptive statistics were used and performed with SAS 9.4 software (SAS Institute Inc., Cary, NC, USA) (13, 14). Wilcoxon-two-sample tests were performed to evaluate associations between possible risk factors and treatment sessions with a bladder volume <200 ml. After Bonferroni adjustment for multiple tests, associations were considered being significant in case of a p-value <0.0064.
Distribution of possible risk factors in the entire cohort.
Results
The mean numbers of fractions (±SD) with a volume <200 ml in the entire cohort, group A, and group B were 29.0±7.0, 28.8±7.6, and 29.2±6.6, respectively (Table II). The corresponding median numbers (plus Q1-Q3) were 32.0 (25.5-34.5), 32.0 (27.0-34.0), and 32.0 (24.0-35.0), respectively (Table II). The difference between group A and group B was not significant (p=0.978, Table II and Figure 1). Moreover, none of the other investigated potential risk factors was significantly associated with mean and numbers of radiotherapy fractions with a bladder volume <200 ml (Table II).
Mean and median numbers of radiotherapy sessions with a bladder volume <200 ml.
Comparison of group A (irradiation with pelvic LN) and group B (irradiation without pelvic LN) with respect to the number of fractions with a bladder volume <200 ml.
Discussion
Definitive conventionally fractionated radiotherapy with total doses up to 80 Gy is a standard approach for high-risk prostate cancer. This treatment can be associated with urinary toxicity, particularly if the bladder volume is comparably small (2-4). In 2006, Pinkawa et al. investigated 80 patients with prostate cancer irradiated with 70.2 Gy (dose per fraction=1.8 Gy) with respect to bowel and urinary function (4). Patients who initially had a bladder volume of >180 ml did not report pain on urination six weeks to six months (median 2 months) following radiotherapy compared to 24% of the patients with a bladder volume <180 ml. In 2019, Grün et al. presented a prospective study of 193 patients irradiated with median 80 Gy (range=74-84 Gy) who received a special training using a bio-feedback method to maintain the bladder volume at 200-300 ml at the CT-simulation and the radiotherapy sessions. It was possible to keep the bladder volume >180 ml, which was associated with less acute genitourinary toxicity (3). In the larger study of Pisani et al. (N=280) patients received 76 Gy (2.0 Gy per fraction) for low-risk prostate cancer and 78 Gy for intermediate-risk or high-risk tumors (2). In addition, in patients with positive pelvic LN or a risk >15% for LN-involvement the pelvic LN were irradiated with 45 Gy (1.8 Gy per fraction). In that study, a bladder volume <200 ml was significantly associated with increased acute urinary toxicity (2). Considering the results of these studies, bladder volumes should be at least 200 ml at the CT-simulation and during radiotherapy. To achieve this goal, the benefit of drinking protocols has been evaluated in several studies (5-10, 15-17). Since adherence to drinking protocols may be a challenge for some patients, a reminder app has been developed and is currently tested in two prospective trials (11, 12). One of these trials focuses on patients with high-risk prostate cancer (12). Until now, only patients irradiated at the prostate and the seminal vesicles alone, i.e., without treatment of the pelvic LN, can be included. Since many high-risk patients receive radiotherapy also to the pelvic LN, the current study protocol may not sufficiently reflect the clinical reality. Therefore, we consider to submit an amendment to the responsible Ethic Committee and open the trial also for patients additionally irradiated at the pelvic LN. Before this can be done, the present retrospective study is required. It should answer the question whether the mean and median numbers of radiation fractions with a bladder volume <200 ml differ between patients receiving radiotherapy of the prostate and the seminal vesicles alone (group B) and patients additionally irradiated at the pelvic LN (group A). According to its results, there is no significant difference between groups A and B with respect to mean and median numbers of radiation fractions with a bladder volume <200 ml during the course of radiotherapy. Moreover, the corresponding numbers in the entire cohort will lead to an update of the sample size required for the prospective trial (12). In addition to irradiation of the pelvic LN, seven characteristics were evaluated for associations with the numbers of radiation fractions with a bladder volume <200 ml (Table II). For none of these characteristics, a significant association was found. In our previous study, patients with a Karnofsky performance score of <90 had a greater number of fractions with suboptimal bladder filling (13). This finding was not confirmed in the present study including a larger number of patients. However, both studies are retrospective in nature and bear the risk of a hidden selection bias. Additional studies are required to properly define the prognostic role of the Karnofsky performance score. Possibly, our prospective trials will be helpful in this context.
In summary, the bladder filling status was not sufficient at the vast majority of the treatment sessions and, therefore, needs particular attention during radiotherapy of high-risk prostate cancer. Since suboptimal bladder filling occurred regardless of irradiation of the pelvic LN, both patients irradiated with and without pelvic LN may be included in the prospective trial. The sample size calculation of that trial needs to be updated.
Acknowledgements
This study is part of the project HeAT (Health Advancing Technologies for Elderly) and has been funded in parts by the European Regional Development Fund through the Interreg Deutschland-Danmark program.
Footnotes
Authors’ Contributions
The Authors contributed to the design of this additional study and/or collection of data. The data were analyzed by an external professional statistician. The article was drafted by D.R., and subsequently reviewed and approved by all Authors.
Conflicts of Interest
The Authors indicate that there are no conflicts of interest related to this study.
Artificial Intelligence (AI) Disclosure
No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.
- Received January 15, 2026.
- Revision received February 2, 2026.
- Accepted February 3, 2026.
- Copyright © 2026 The Author(s). Published by the International Institute of Anticancer Research.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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