A prospective pilot study of urine microRNA as a biomarker of urinary radiation toxicity following MRI-guided prostate stereotactic body radiotherapy.

Introduction: Urinary toxicities are common following prostate radiotherapy and can impair quality of life. New biomarkers are needed that can predict the risk of urinary toxicity following MRI guided stereotactic body radiotherapy (MR-SBRT) to assist with selection of the most appropriate radiotherapy treatment approach. We aimed to identify urine miRNA biomarkers of radiation-induced urinary toxicities. Methods: Ten patients undergoing MR-SBRT were enrolled on a prospective biorepository protocol and urine specimens were collected before, at the final fraction and 2-4 months following radiotherapy. RNA was isolated and microRNA sequencing was performed followed by qPCR for confirmation of microRNA expression changes. Differences in microRNA expression were assessed with regard to timepoint, cancer risk category and urinary toxicity. Results: Both sequencing and qPCR showed that expressions of miR-26a-5p and miR-95-3p decrease during MR-SBRT and increase during early follow up. miR-204-3p and miR-192-5p changed differently in patients with and without urinary radiation toxicity. Expression of miR-375-3p was lower in patients with higher risk category (NCCN unfavorable intermediate to high risk or recurrent/metastatic) at all timepoints and decreased during and after MR-SBRT, especially in patients with a lower risk category (NCCN low to favorable intermediate risk) of prostate cancer. Discussion: Urine microRNA analysis is feasible and may identify biomarkers linked to radiation-induced urinary toxicity and prostate cancer severity. The findings of this pilot study are limited by the sample size and should be prospectively validated.