The bladder wall has three well-defined layers including the mucosa (urothelium, basement membrane, and lamina propria), the muscularis propria, and the adventitia/serosa.

Human urothelium is considered a transitional epithelial tissue that its cellular differentiation increased from basal cells at basement membrane to surface cells of superficial or apical layer [38]. Surface cells known as umbrella cells are joined to each other with tight cell membrane junctions. The apical surface of umbrella cells is almost entirely covered by rigid plaques (known as the asymmetric unit membrane or AUM) consisting of a group of transmembrane proteins called uroplakins (UP), i.e., UPIa, UPIb, UPII, and UPIII [39–42].

Between these particles, UPIII is a main subunit of urothelial plaques that play a key role in urothelial structure [43].

The urothelium also contains a luminal negatively charged glycosaminoglycan (GAG) called a mucous layer that covers the umbrella cells on top of the apical membrane [44].

GAGs can be in a non-sulfated form like hyaluronic acid (HA) or a sulfated form like heparan sulfate and heparin, chondroitin sulfate (CS), dermatan sulfate, and keratan sulfate [45].

Tight junctions between umbrella cells, the urothelial plaques, and the glycosaminoglycan (GAG) layer make an efficient barrier against electrolyte and nonelectrolyte urine concentrations in bladder mucosa [46, 47].

Data on underlying mechanisms of acute radiation effects in the urinary bladder are limited. The urothelium barrier of the bladder is affected by radiation. Decrease in the number of umbrella cells [48], loss of the superficial UPIII layer [48], and GAG layer damage [49, 50] have been reported in patients with radiation cystitis. However, due to slow cell turnover rate of bladder epithelium (in the range of 42–350 days) [46, 51], gross tissue breakdown does not occur in early radiation cystitis [48].

Following the urothelium barrier impairment, urine substances infiltrate the bladder wall and produce more injuries by induction of the inflammatory response, mast cell proliferation, activation, degranulation and histamine release, vasodilatation, and also erythematous swelling [48]. Urine ion content, histamine, and other inflammatory substances irritate nerve terminals within the bladder wall [52]. This damaged barrier is also susceptible to secondary infection that could produce more injury [53].

Molecular responses including increased synthesis of intercellular adhesion molecules (ICAM1) [54] and prostaglandin [55] resulted in increased inflammatory reactions and detrusor muscle edema and decreased the bladder capacity. All these events finally produce overactive bladder symptoms.

The first symptoms of early radiation effects on the urinary bladder usually occur 4–6 weeks after treatment begins. They are usually mild and transient. It has been found that grade 2 or higher acute bladder toxicity may take an average of 6 weeks (range 2–21 weeks) after the completion of treatment to improve [55, 56], but 5–20% of patients may develop persistent late bladder damage from 6 months to 10 years after treatment [57]. The risk of late bladder damage depends on pre-radiation therapy genitourinary morbidity [4], smoking history (≥1 pack per day) [58], body mass index(>30 kg/m²) [58], any kind of procedure before radiation therapy [59], and a high dose per fraction [60] that go beyond the scope of this book.

The risk of acute bladder damage increases with pre-radiation therapy genitourinary morbidity score [4, 61].

Chemotherapy administered concurrently with radiation therapy has not been shown to significantly increase the risk of acute bladder complications [12, 34, 62], whereas use of hormonal therapy in prostate cancer has been associated with more acute genitourinary complications [4, 61].

Radiation total dose, maximum bladder dose, and higher volume of bladder exposed to radiation are associated with a higher risk of acute toxicity [29, 63, 64]. The treatment time and dose per fraction have not been reported to be related with acute bladder injury [56, 65].

Other clinical factors such as age, transurethral resection of the prostate before radiation therapy, diabetes mellitus, and smoking have not been reported to be associated with acute bladder toxicity [4, 56], although some of them as previously mentioned are related to late toxicity.

Radiation cystitis symptoms during the early reaction phase include frequency, nocturia, urgency, dysuria, and hematuria [66].

Bacterial infection may complicate the clinical picture.

Direct examination of the urothelium demonstrates mucosal edema, hyperemia, and inflammation.

Radiation Therapy Oncology Group (RTOG) radiation induced bladder morbidity scoring criteria presented in Table 16.1 [67].

Acute symptoms of radiation injury to the bladder are usually self-limited and manageable [68], but prevention of these symptoms is important because they are associated with a marked impact on quality of life and increased occurrence of late toxicities [56].

Generally, all patients with acute radiation cystitis symptoms should be encouraged to increase fluid intake. It can result in urine irritant dilution and prevent urinary tract infections [75].

Acute radiation cystitis often responds to symptomatic therapy. Anticholinergics have been the mainstay of management for storage symptoms such as frequency. Other treatment options include analgesics like phenazopyridine and alpha-1 blocker [66].