Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.
To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.
This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality.
For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%.
Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01).
The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT.
ClinicalTrials.gov Identifier: NCT04189913.
JAMA oncology. 2023 Feb 09 [Epub ahead of print]
Neil F Mariados, Peter F Orio, Zvi Schiffman, Thanh John Van, Alexander Engelman, Rizwan Nurani, Steven M Kurtzman, Escarlata Lopez, Michael Chao, Thomas P Boike, Alvaro A Martinez, Glen Gejerman, John Lederer, John E Sylvester, Gregory Bell, Douglas Rivera, Neal Shore, Katie Miller, Boris Sinayuk, Michael L Steinberg, Daniel A Low, Amar U Kishan, Martin T King
Cancer Care of Western New York, Buffalo, New York., Brigham and Women's Hospital, Boston, Massachusetts., Houston Metro Urology, Houston, Texas., Florida Urology Partners, Tampa, Florida., Western Radiation Oncology, Campbell, California., Vithas La Milagrosa Hospital, Calle de Modesto Lafuente, Madrid, Spain., Ringwood Private Hospital, East Victoria, Australia., GenesisCare, Troy, Michigan., New Jersey Urology, Saddle Brook, New Jersey., The Cancer Center of Hawaii, Honolulu., GenesisCare, Lakewood Ranch, Florida., Austin Cancer Center, Austin, Texas., Carolina Urologic Research Center, Myrtle Beach, South Carolina., M Squared Associates, New York, New York., Rhode Island Medical Imaging, Warwick, Rhode Island., University of California, Los Angeles.