In a study reported in JAMA Oncology, Mariados et al found that use of a hyaluronic acid rectal spacer reduced radiation exposure of the rectum—and reduced the incidence of grade ≥ 2 gastrointestinal (GI) toxicity—in patients receiving hypofractionated radiation therapy for prostate cancer.
Study Details
The trial included 201 patients from sites in the United States, Australia, and Spain with biopsy-proven T1 to T2 disease, Gleason score ≤ 7, and prostate-specific antigen level ≤ 20 ng/mL diagnosed within the prior 9 months. They were randomly assigned 2:1 between March 2020 and June 2021 to receive hypofractionated radiotherapy with (n = 136) or without (n = 65) use of the spacer. The spacer (9–12 cc) was injected between the Denonvilliers fascia and the anterior rectal wall. The planning target volume prescription dose was 60 Gy in 20 fractions.
For the primary outcome, it was hypothesized that the proportion of patients in the spacer group with a ≥ 25% reduction in the rectal volume receiving 54 Gy (V54) would exceed the minimally acceptable rate of 70% (significance level defined as P < .03). For the secondary outcome, it was hypothesized that the spacer group would have a noninferior rate of acute (within 3 months) grade ≥ 2 GI toxic effects vs the control group, with a margin of 10%.
Key Findings
For the primary outcome, 131 (98.5%, 95% confidence interval [CI] = 94.7%–99.8%) of 133 evaluable patients in the spacer group had a ≥ 25% reduction in rectum V54, significantly exceeding the minimally acceptable rate of 70% (P < .001). The mean reduction was 85.0% (standard deviation = 20.9%).
For the secondary outcome, 4 (2.9%) of 136 patients in the spacer group vs 9 (13.8%) of 65 patients in the control group had grade ≥ 2 GI toxic effects within 3 months (difference = −10.9%, 95% upper confidence limit = −3.5, P = .01); since the upper confidence limit was less than 0, use of the spacer was associated with a significant reduction in acute toxicity. The grade ≥ 2 GI toxic effects consisted of proctitis, constipation, diarrhea, and hemorrhoids in one patient each in the spacer group, and proctitis in four patients, diarrhea in three, hemorrhoids in two, and rectal hemorrhage in one in the control group, with one patient experiencing two adverse events.
The investigators concluded, “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 radiotherapy.”
Martin King, MD, of Brigham and Women's Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Palette Life Sciences. For full disclosures of the study authors, visit jamanetwork.com.
