Radiation for
pelvic cancers can result in severe bladder damage and radiation
cystitis (RC), which is characterized by chronic
inflammation,
fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced
cystitis in cancer survivors using urine samples from
prostate cancer survivors with history of
radiation therapy. 94 urine samples were collected from
prostate cancer survivors with (n = 85) and without (n = 9) history of
radiation therapy. 15 patients with radiation history were officially diagnosed with radiation
cystitis. Levels of 47 different
proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation
cystitis diagnosis, symptom scores or
hematuria. Statistical analysis was performed using Welch's t-test. In
prostate cancer survivors with history of
radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and
VEGF-A were detected in patients that received a radiation
cystitis diagnosis. These
proteins were also increased in patients suffering from
hematuria or high symptom scores. No inflammatory
proteins were detected in the urine, except in patients with gross
hematuria and end stage radiation
cystitis. Active
fibrosis and vascular distress is detectable in the urine through elevated levels of associated
proteins.
Inflammation is only detected in urine of patients with end-stage radiation
cystitis disease. These results suggest that
fibrosis and vascular damage drive the development of radiation
cystitis and could lead to the development of more targeted treatments.