Background: Despite improvements in irradiation techniques, pelvic radiotherapy is responsible for acute and late adverse events in the bladder, defined as radiation cystitis (CysR). The early symptoms of bladder lesions secondary to pelvic irradiation are likely to occur during treatment or after radiotherapy in approximately 50% of irradiated patients. Acute radiation-related injuries are the first step of the fibrosis process. Fibrosis causes loss of bladder function and has a significant impact on the quality of life of the patients.The pathophysiology of CysR is not well understood, in particular because of the risks of complications caused by accessing the bladder tissue after irradiation, thereby limiting our ability to investigate this process and develop treatments. The main objective of our study is to assess the correlation of biologic biomarkers with the intensity of acute CysR and the quality of life of patients, evaluated with the digital telemonitoring platform Cureety. Methods: Patients with intermediate-risk localized prostate cancer and eligible for localized radiotherapy will be included. Inflammatory biomarkers will be analyzed on urine and blood samples before the initiation of radiotherapy, at week 4, 12 and 48 of irradiation, by quantitative methods such as the Multiplex Luminex assay, cytometry in flow and enzyme-linked immunosorbent assay ELISA. We will also characterize the gut and urinary microbiota in stool and urine samples using 16S rRNA sequencing technology. This is in order to assess the impact of the fecal and urinary microbiota in acute CysR. Between sample collection visits, patients will answer various questionnaires relating to the symptoms of radiation cystitis (IPSS), adverse events and quality of life (FACT-P), using the digital telemonitoring platform Cureety. Upon receipt of the questionnaires, an artificial intelligence algorithm will process the information and classify the patients according to the severity of symptoms and adverse reactions reported in accordance with CTCAE / IPSS. This will ultimately allow us to correlate urinary, blood and fecal biomarker levels with the severity of acute CysR symptoms and the quality of life reported by the patients. Conclusion: This prospective study is the first to explore the overexpression of inflammatory proteins in fluid biopsies from patients with symptoms of acute CysR. In addition, the 1-year post-treatment follow-up will allow us to predict which patients are at risk for late CysR and to stratify these patients towards radioprotective treatment. The results of this study will allow us to develop strategies to limit radiation damage to the bladder and improve the quality of life of patients. Clinical trial information: 2021A0319635.