Purpose: The Hydrogel Spacer Prospective Randomized Pivotal Trial achieved mean rectoprostatic spacing of 12.6 mm resulting in lowering of rectal V70 from 12.4% (without spacer) to 3.3% (with spacer) in patients with glands up to 80 cm3 . The value of this approach in patients with larger glands is inadequately established. This study assesses the feasibility and dosimetric outcomes of perirectal spacing in patients with prostate cancer with larger glands (\u3e80 cm3 ). Methods and Materials: Between January 2017 and December 2019, 33 patients with prostate glands \u3e80 cm3 (mean 108.1 cm3 ; range, 81.1-186.6 cm3 ) were treated, 15 with glands \u3e80 to 100 cm3 and 18 \u3e100 cm3 . Median follow-up was 10 months (range, 3-26). The median international prostate symptom score was 9 (range, 1-18). Hydrogel was placed under local anesthesia in all cases. Treatment modality included intensity modulated radiation therapy in 15 and proton therapy (PT) in 18 patients. Treatment targeted the prostate plus seminal vesicles in 21 patients and 12 also had elective nodal irradiation. Conventional fractionation (CF) to 78 Gy in 39 fractions was used in 16 and moderate hypofractionation (HF) to 70 Gy in 28 fractions in 17 patients. Results: In the CF group, mean rectum (r) V75, 70, 60, 50 was 0.87%, 2.25%, 5.61%, and 10.5%, respectively. For glands \u3e80 to 100 cm3 and \u3e100 cm3 , rV70 was 2.55% and 2%, respectively. In HF patients, mean rV65, 63, 60, and 50 was 1.67%, 2.3%, 3.4%, and 8.6%. For glands \u3e80 to 100 cm3 and \u3e100 cm3 , rV63 was 2% and 2.56%, respectively. Overall, the mean midgland rectoprostatic hydrogel separation was 9.3 mm (range, 4.7-19.4 mm). All patients tolerated treatment well; no acute grade 2 or higher adverse gastrointestinal events were observed. Conclusions: Hydrogel placement is feasible in prostate glands larger than 80 cm3 with favorable dosimetric outcomes
