Presentation Authors: Bernadette M.M. Zwaans*, Royal Oak, MI, Heinz E. Nicholai, Santiago, Chile, Klaudia Stangel-Wójcikiewicz, Krakow, Poland, Michael B. Chancellor, Laura E. Lamb, Royal Oak, MI
Introduction: Radiation cystitis (RC) is a debilitating side effect from radiation therapy that develops in approximately 10% of pelvic cancer survivors who received radiation therapy. Histologically, radiation therapy causes bladder inflammation, fibrosis and vascular damage. We previously reported elevated angiogenic growth factors in the urine of RC patients, hereby indicating ongoing vascular damage in these patients. Here, we investigated the effect of radiation therapy on fibrotic factors (e.g. MMP's and TIMP's) in the urine. We hypothesize that radiation-induced fibrosis in the bladder is detectable in the urine through altered protein levels of fibrotic factors. Together with our angiogenic growth factor panel, these fibrotic factors can serve as an individualized diagnostic tool for early diagnosis of RC prior to the onset of symptoms.
Methods: Urine samples were collected from prostate cancer survivors with a history of external beam therapy. Urine of healthy men and of prostate cancer survivors that did not receive radiation therapy were used as normal control samples. Levels of fibrotic factors in the urine were measured using Luminex Multiplex assay (Millipore).
Results: 76 prostate cancer survivors with a history of radiation therapy provided a urine sample and filled out a survey on urinary symptoms. Urine samples were tested for a panel of fibrotic factors. MMP-9, MMP-10, TIMP-1, TIMP-2, PAI-1 and Cathepsin-D were detectable in human urine samples and were elevated when compared to RC status, frequency, IC/BPS symptom score, and/or the presence of hematuria.
Conclusions: RC can develop in pelvic cancer survivors and is characterized in part by bladder fibrosis and vascular damage/hemorrhaging. RC is diagnosed by ruling out other conditions and through invasive procedures (e.g. cystoscopy). Our studies indicate radiation-induced changes in fibrotic factors that are detectable in the urine. These factors could be useful biomarkers in the era of personalized medicine for early non-invasive detection of radiation cystitis.
Source of Funding: This project was in part supported by the U Can-Cer Vive Foundation and the NIDDK K01 career development award (DK114334).