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Recent advances in radiation therapy have shown promising cancer control for high-risk (HR) prostate cancer (PCa) patients undergoing stereotactic body radiotherapy (SBRT) plus supplemental pelvic intensity-modulated radiation therapy (IMRT). Unfortunately, radiation dose escalation increases the probability of late gastrointestinal (GI) toxicities. High radiation dose to the anterior rectal wall is likely responsible for this increase. This study investigates the impact of rectal spacer utilization on the incidence of GI toxicities following prostate SBRT with supplemental pelvic IMRT. Between February 2016 to June 2023 81 HR PCa patients were treated with prostate SBRT (19.5 Gy in 3 fractions) followed by supplemental pelvic IMRT (37.5 Gy – 45 Gy in 15-25 fractions). Rectal spacer (SpaceOAR/SpaceOAR Vue) placement was at the discretion of the treating physicians and occurred at the time of required fiducial placement. Posterior extracapsular extension (ECE) was a contraindication to spacer placement. Toxicity assessments were prospectively graded at three-month intervals for one year, followed by six-month interval for a year and then yearly, adhering to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE V4). Cumulative incidence was determined at 3 years follow up. The median follow-up was 25 months. Twenty patients underwent rectal spacer placement while 61 did not. There were no adverse events or treatment delays related to spacer placement. In patients without rectal spacer placement, the cumulative rate of G2 GI toxicity was 34%, and G3 GI toxicity was 2%. In the rectal spacer placement group, the cumulative rate of G2 GI toxicity was 5% and no G3 GI toxicity was observed. This study highlights the role of well-placed rectal spacers in reducing the incidence of GI toxicities in men undergoing SBRT with supplemental pelvic IMRT. Limitations of this study include that patient with more advanced disease were excluded from spacer placement. Future studies should look at randomization of subjects. [ABSTRACT FROM AUTHOR]