PurposeTo evaluate the technical feasibility, acute and late genitourinary (GU) toxicity, and gastrointestinal toxicity after high-dose-rate (HDR) brachytherapy as monotherapy in one fraction with transperineal hyaluronic acid injection into the perirectal fat to displace the rectal wall away from the radiation sources to decrease rectal toxicity. Methods and MaterialsBetween April 2008 and January 2010, 40 consecutive patients were treated with favorable clinically localized prostate cancer; the median followup was 19 months (range, 8–32). No patients received external beam radiation, and 35% received hormone therapy before brachytherapy. All patients received one implant and one fraction of HDR. Fraction dose was 19Gy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, Version 4.0. ResultsAll patients tolerated the implantation procedure very well with minimal discomfort. No intraoperative or perioperative complications occurred. Acute toxicity Grade 2 or more was not observed in any patients. No chronic toxicity has been observed after treatment. Logistic regression showed that the late Grade 1 GU toxicity was associated with D90 (p=0.050). The 32-month actuarial biochemical control was 100% and 88%, respectively (p=0.06) for low- and intermediate-risk groups. ConclusionsThis is the first published report of the use of HDR brachytherapy as monotherapy in one fraction for patients with favorable-risk prostate cancer. This protocol is feasible and very well tolerated with low GU morbidity, no gastrointestinal toxicity, and the same level of low-dose-rate biochemical control at 32 months.