Session Item

Radiation-induced cystitis (RC) may arise when pelvic tumors, such as prostate cancer, are treated with radiotherapy (RT). The modeling of RT-induced urinary toxicity represents a complex topic, which is attracting increasing interest in radiotherapy. A thorough understanding of the mechanisms underlying RC is still largely lacking, and in vivo preclinical research has a decisive role in improving the knowledge concerning the causes and, hence, the possible solutions in order to at least limit its clinical impact.

To resemble this condition, we set up a rat animal model, which allowed us to follow the radiation-cystitis development over time. 

We employed a range of techniques to monitor the RC cystitis, i.e. ultrasound imaging system, used to measure the bladder wall thickness, cystometry, to assess the bladder compliance and immunohistochemistry (IHC) to investigate structural alteration, vascularization and fibrosis. The anti-androgen Degarelix was used to mitigate the inflammatory radiation effect since experimental models previously developed at our Institute had highlighted both the anti-inflammatory and antifibrotic effects of an antiandrogen in a rat model of bladder damage.

Radiation induced bladder wall thickness increased over time and it was especially relevant after high doses RT (Figure 1) in the range of 35-40 Gy (single fraction). We then evaluated the RT-induced functional impairment of bladder compliance by monitoring the urodynamic parameters (Figure 2): at late time points (6-8 months), when fibrosis developed and the bladder capacity was reduced, a progressive reduction of micturition volume and a parallel increase of micturition events over time after RT were observed. In addition, preliminary structural assessment performed to confirm the observed functional impairment, revealed an increased vascularization (increased amount of CD31 positive vessels) and fibrosis (increased collagen I deposition). The Degarelix pretreatment prevented both the radiation-induced impairment of urodynamic parameters and structural alteration. Specifically, it increased the mean volume voided per micturition, the micturition interval and reduced the frequency, when compared to the same parameters observed in the RT-only treated animals. Moreover, it counteracted the neovascularization and the fibrosis processes.

Overall our data demonstrated that it is possible to set up and optimize a rat model of RC, resembling the disease in human beings, which allows to monitor its onset and development. The pretreatment of the animals with Degarelix thwarted the radiation-induced functional and structural alteration of the bladder, highlighting the potential of this approach to be exported to patients.

Figure 1

Figure 2