title: Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial.
abstract: SpaceOAR, a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years.
  
  
  
  Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds.
  
  
  
  The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02).
  
  
  
  The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.
authors.affiliation: Texas Oncology, Texas Center for Proton Therapy, Irving, Texas. Electronic address: Daniel.Hamstra@gmail.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.affiliation: Associated Medical Professionals of NY, PLLC, Syracuse, New York.
authors.forename: Neil
authors.initials: N
authors.lastname: Mariados
authors.affiliation: 21st Century Oncology, Inc, Lakewood Ranch, East Bradenton, Florida.
authors.forename: John
authors.initials: J
authors.lastname: Sylvester
authors.affiliation: Western New York Urology Associates, LLC, Doing Business as Cancer Care of WNY, Cheektowaga, New York.
authors.forename: Dhiren
authors.initials: D
authors.lastname: Shah
authors.affiliation: The Urology Center of Colorado, Denver, Colorado.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Karsh
authors.affiliation: Chesapeake Urology Associates, Doing Business as Chesapeake Urology Research Associates (The Prostate Center), Owings Mills, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Hudes
authors.affiliation: Arizona Oncology Services Foundation, Phoenix, Arizona.
authors.forename: David
authors.initials: D
authors.lastname: Beyer
authors.affiliation: Urological Surgeons of Northern California Inc, Campbell, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Kurtzman
authors.affiliation: The Research Foundation of State University of New York/State University of New York Upstate Medical University, Syracuse, New York.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bogart
authors.affiliation: Peninsula Cancer Center, Poulsbo, Washington.
authors.forename: R Alex
authors.initials: RA
authors.lastname: Hsi
authors.affiliation: Urology Nevada, Reno, Nevada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kos
authors.affiliation: University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Rodney
authors.initials: R
authors.lastname: Ellis
authors.affiliation: Sutter Health Sacramento Sierra Region, Doing Business as Sutter Institute for Medical Research, Sacramento, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Logsdon
authors.affiliation: Advanced Radiation Centers of New York, Lake Success, New York.
authors.forename: Shawn
authors.initials: S
authors.lastname: Zimberg
authors.affiliation: Oregon Urology Institute, Springfield, Oregon.
authors.forename: Kevin
authors.initials: K
authors.lastname: Forsythe
authors.affiliation: University of Rochester, Rochester, New York.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CentraState Medical Center, Freehold, New Jersey.
authors.forename: Edward
authors.initials: E
authors.lastname: Soffen
authors.affiliation: Carolina Regional Cancer Center, LLC, 21st Century Oncology, Inc, Myrtle Beach, South Carolina.
authors.forename: Patrick
authors.initials: P
authors.lastname: Francke
authors.affiliation: 21st Century Oncology, Inc, Fort Meyers, Florida.
authors.forename: Constantine
authors.initials: C
authors.lastname: Mantz
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossi
authors.affiliation: The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Theodore
authors.initials: T
authors.lastname: DeWeese
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault-Newton
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Fischer-Valuck
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Anupama
authors.initials: A
authors.lastname: Chundury
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Hiram
authors.initials: H
authors.lastname: Gay
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Walter
authors.initials: W
authors.lastname: Bosch
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
mesh_terms: D000328:Adult; D000368:Aged; D015984:Causality; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000523:psychology / Q000532:radiotherapy*; D011788:Quality of Life / Q000523:psychology; D011832:Radiation Injuries / Q000453:epidemiology* / Q000517:prevention & control* / Q000523:psychology; D011835:Radiation Protection / Q000295:instrumentation / Q000706:statistics & numerical data*; D020266:Radiotherapy, Conformal / Q000379:methods / Q000523:psychology / Q000706:statistics & numerical data; D061089:Radiotherapy, Image-Guided / Q000523:psychology / Q000706:statistics & numerical data; D012002:Rectal Diseases / Q000453:epidemiology* / Q000517:prevention & control* / Q000523:psychology; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology