Persistent Bothersome Urinary Frequency Following Stereotactic Body Radiation Therapy (SBRT) for Clinically Localized Prostate Cancer: Rationale for Prophylactic β3-Adrenergic Agonist in Men with Elevated Baseline International Prostate Symptom Scores

Jennifer Zack¹Min Ji Koh¹Emily Lindbloom¹Timothy O'Connor¹Kelly Gaudian²Alan Zwart²Malika Danner²Deepak Kumar³Simeng Suy⁴Ryan Andrew Hankins⁵Sean Collins^4*

• ¹School of Medicine, Georgetown University, Washington, D.C., United States
• ²Department of Radiation Oncology, MedStar Georgetown University Hospital, Washington, United States
• ³Biotechnology Research Institute, North Carolina Central University, Durham, United States
• ⁴Department of Radiation Oncology, University of South Florida Morsani College of Medicine, Tampa, United States
• ⁵Department of Urology, MedStar Georgetown University Hospital, Washington, United States

Introduction: Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer has been associated with prolonged acute obstructive and irritative lower urinary tract symptoms (LUTS). Prophylactic alpha-adrenergic antagonists have been used therapeutically to prevent obstructive symptoms in patients undergoing prostate SBRT, however irritative symptoms may be better addressed with beta 3-adrenergic receptor agonists, which are shown to be safe and effective in men with overactive bladder (OAB). Objective: This study retrospectively examines the pattern of bothersome urinary frequency associated with SBRT to determine which patients would have potentially benefitted from prophylactic beta 3-adrenergic receptor agonist. Methods: Patients with clinically localized prostate cancer who underwent prostate SBRT (n=1676) were followed for 3 months post-treatment to evaluate for bothersome urinary frequency, which was assessed by question 4E on the EPIC-26. Answers to question 4E and tamsulosin usage were recorded at regular follow-ups to assess, and demographic factors as well as baseline prostate volume, alpha-adrenergic antagonist usage and IPSS score severity were used as modifiers. Results: Using the IPSS questionnaire to determine baseline LUTS, most patients reported moderate urinary symptoms (53%), followed by mild (34%) and severe (13%). Patients endorsed increased irritative LUTS at 1-month post-SBRT, with similar rates of frequency at 3 months compared to baseline. Patients with moderate and severe urinary symptoms per the baseline IPSS were more likely to endorse bothersome urinary frequency at one month post SBRT (EPIC-26 Q4E; OR 2.58 and 10.2 respectively) compared to those with mild symptoms. No significant differences were found in urinary frequency between patients who used and did not use an alpha antagonist at baseline. Conclusions: Bothersome post-SBRT urinary frequency persists 1-month post-SBRT. Baseline LUTS predicts bothersome post-treatment urinary frequency. Prophylactic alpha-adrenergic antagonists do not protect against bothersome acute urinary frequency. This paper makes the case urinary frequency may be better addressed with a prophylactic beta-3 agonist, like vibegron, which is designed to treat storage-related LUTS concerns.