Accumulated bladder wall dose and urinary toxicity 133 Introduction Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with low- and intermediate-risk prostate cancer. With this form of extreme hypofractionation, patients are commonly treated with five fractions of 7.25 Gy over the course of 1-2.5 weeks.1 Oncological outcomes after SBRT are excellent, with 7-year biochemical failure-free survival rate of 93.7%.1 Severe toxicity rates after prostate SBRT are low, with £ 1% combined genitourinary (GU) and gastrointestinal (GI) grade ³ 3 toxicity.1 However, physician-reported incidences of acute grade 2 GU toxicity ranged between 21-28% in phase-3 trials comparing conventional treatment with SBRT.2,3 Also, patient-reported outcome measures (PROMs), such as the International Prostate Symptom Score (IPSS) questionnaire, have shown clinically relevant side acute effects in a significant number of patients.3–7 The introduction of magnetic resonance imaging (MRI)-guided linear accelerators (MR-Linac) has enabled intrafraction MR imaging and daily plan adaptation.8,9 While the potential clinical benefits of MRI-guided treatment have yet to be established, the incorporation of high-quality MR imaging provides more detailed anatomical information shortly before and during the treatment compared to conventional systems.10–12 With online plan adaptation, the treatment plan is adapted to fit the daily anatomy, thereby potentially increasing treatment effectiveness while also reducing radiation dose to organs-at-risk (OARs).9 Furthermore, the daily repeated imaging and re-planning allowmore accurate estimation of the actual delivered dose.13,14 Additionally, the use of high-quality MR imaging enables identification of soft-tissue substructures, such as the bladder wall.15 Currently, evidence on the relationship between the actual delivered dose to urinary structures and acute urinary toxicity after prostate cancer SBRT is scarce as many studies considered pre-treatment plan data only.16,17 The aim of the current study was to gain insight into the dose-effect relationship between the accumulated bladder and bladder wall dose and patient-reported acute urinary toxicity in prostate cancer patients treated with MRI-guided SBRT. Materials and methods Patients and treatment procedures For this study, prostate cancer patients treated with five fractions of 7.25 Gy on a 1.5 T MR-Linac (Unity, Elekta AB, Stockholm, Sweden) between March 2020 and May 2021, who provided informed consent for the use of their data within the prospective Utrecht Prostate Cohort (UPC) study (NCT04228211), were identified. In the UPC study, patients with primary localised prostate cancer are included before treatment and prospectively followed over time. After exclusion of 29 patients with missing baseline and/or follow-up IPSS data, 132 patients were included. 7
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