*2.1. Acute Radiation Cystitis*

Acute radiation cystitis is defined as any adverse event occurring during or up to threemonths after the end of radiation therapy (the threshold of sixmonths was also proposed). Its incidence is estimated at nearly 50% following pelvic irradiation at full curative doses (e.g., prostate or locally advanced cervical cancer treatment). Clinical symptoms may include increased urinary urgency and frequency (pollakiuria), both during the day and at night, dysuria, but also cystalgia with bladder spasms, and hematuria, albeit rarely at this early stage. An international grade classification ranging from 1 to 5 can be used to assess the severity and impact on the quality of life (Figure 1) [3]. Acute radiation tissue injury to the bladder is caused primarily by damage to the bladder mucosa. It involves an acute inflammatory response and tissue edema. Urothelial regeneration thus comes to a halt, and the epithelium is desquamated with no regeneration, which results in urothelial lesions making the bladder vulnerable to trauma and infections [4]. These lesions are characterized by edema, hyperemia and inflammation of the mucous membrane. In most of the cases, the prognosis is favorable, as these reactions usually disappear spontaneously within fourto sixweeks after the completion of radiation therapy [4,5], but an interruption of radiation therapy may be considered in case of severe grade 3–4 symptoms. Such treatment disruptions may potentially lead to a decrease in tumor control because of an increase in overall treatment time and should, therefore, be discussed on an individual basis [6].

*Cells* **2021**, *10*, x FOR PEER REVIEW 3 of 20

**Figure 1.** Illustration of radiation cystitis (RC) and clinical management adapted with "Modeling and treatment of radiation cystitis [7], development of RC after radiotherapy (**A**), in the acute phase (infiltration of immune cells into the lamina propria (LP) and depletion of the urothelium (UE)), in latent phase (proliferation of fibroblasts with hematuria, dilation of vessels, bleeding, decrease in the detrusor muscle layer (D) and production of collagen in LP and extracellular matrix(ECM). (F: fibroblast, V: vessel, M: muscle cells, C: collagen fibers, I: immune cells) (**B**) Clinical management during **Figure 1.** Illustration of radiation cystitis (RC) and clinical management adapted with "Modeling and treatment of radiation cystitis [7], development of RC after radiotherapy (**A**), in the acute phase (infiltration of immune cells into the lamina propria (LP) and depletion of the urothelium (UE)), in latent phase (proliferation of fibroblasts with hematuria, dilation of vessels, bleeding, decrease in the detrusor muscle layer (D) and production of collagen in LP and extracellular matrix(ECM). (F: fibroblast, V: vessel, M: muscle cells, C: collagen fibers, I: immune cells) (**B**) Clinical management during the acute phase of CR. (**C**) Clinical management during the latent phase of CR. \* corresponds to cascade treatments of grades 2 to 4 according to CTCAE version 5 [3].
