A REminder App to Optimize Bladder FILLing in Patients with ProstAte Cancer Receiving HYPO-fractionated Radiotherapy

Prostate cancer is one of the most common solid malignancies worldwide. Many patients receive normo-fractionated (5 × 2.0 Gy per week) external beam radiotherapy (EBRT) alone with 74-80 Gy in 37-40 fractions over 7.5 to 8 weeks Since three randomized trials have demonstrated non-inferiority of moderately hypo-fractionated RT (HF-RT) when compared to normo-fractionated EBRT, the use of HF-RT has become more popular, particularly for patients with low or intermediate prostate cancer. Two of three randomized trials used 20 x 3.0 Gy for HF-RT. Radiotherapy of prostate cancer, irrespective of the type of fractionation, may be associated with significant acute urinary toxicity such as cystitis, particularly if the volume of the urinary bladder is small. Three studies showed that bladder volumes <200 ml or <180 ml, respectively, were associated with increased acute or late urinary toxicity. Therefore, it appears important to achieve bladder volumes >200 ml at as many radiation fractions as possible. In a very recent study of our group that investigated the bladder volumes at each of the 20 fractions in 76 patients receiving HF-RT alone with 20 x 3.0 Gy, the mean and median numbers of radiation fractions with bladder volumes <200 ml were 13.4 (SD, standard deviation = 6.7) and 16.0 (IQR, interquartile range 8.0 - 19.0) fractions, respectively. Whereas in the subgroup of 24 patients with pre-radiotherapy bladder volume of at least 200 ml the mean and median numbers of radiation fractions with bladder volumes <200 ml were only 7.9 (SD = 5.9) and 8.0 (IQR 3.5 - 11.0), respectively, the mean (16.0, SD = 5.5) and median (19.0, IQR 14.5 - 20.0) were significantly higher (p<0.001) in the subgroup of 52 patients with pre-radiotherapy bladder volumes <200 ml. Therefore, there is a medical need for improvement especially in the latter subgroup. Several studies investigated the role of drinking protocols. Patients were asked to drink a certain amount of water prior to the planning computed tomography (CT-simulation) and the radiotherapy sessions. Drinking a certain amount of water at a specific point in time may require considerable discipline from the mainly elderly or very elderly patients. These considerations led to the idea of developing a mobile application (app) that reminds the patients prior to each radiation session to drink a certain amount of water. The present study investigates the number of radiation fractions with bladder volumes <200 ml in a prospective cohort of patients treated with HF-RT using a such a reminder app. In addition, the study evaluates whether the use of the reminder app leads to a significant reduction of the proportion of fractions with bladder volumes <200 ml in patients receiving HF-RT when compared to a historical control group not supported by an app.

Endpoints: The primary endpoint is the number of radiation fractions with bladder volumes <200 ml at the end of radiotherapy. In addition, patient satisfaction with the reminder app and the impact of the reminder app on the use of health technology are evaluated.

General trial design and duration: This is a single-arm prospective study, which will investigate the effect of a reminder app on the number of radiation fractions with bladder volumes <200 ml during a course of HF-RT (20 x 3.0 Gy over 4 weeks) for definitive treatment of prostate cancer in comparison to a historical control group of 52 patients. The historical control group is considered appropriate for the comparison to the cohort of the present study, since all patients of the control group were treated very recently (2022-2024) with HF-RT alone in centers participating in the present study and received a Cone Beam Computed Tomography prior to each radiation fraction, which allowed assessment of the bladder volume as precisely as in the present study.

Recruitment of all 27 patients is planned to be completed within 20 months. The follow-up will end directly after the radiotherapy course, which is scheduled to take 4 weeks. This equals a total running time for the study of 21 months.

In accordance with the previous study assessing the number of fractions with bladder volumes <200 ml during a course of HF-RT for definitive treatment of prostate cancer, the following characteristics will be recorded to allow adequate comparison with the historical control group: Initial (pre-radiotherapy) bladder volume, body-mass index (BMI), age, prostate volume prior to radiotherapy, Karnofsky performance score (KPS), level of prostate-specific antigen (PSA), Gleason score, T-stage, risk group of prostate cancer, and antihormonal therapy.