To Space or Not to Space: The EPIC Question for Prostate Stereotactic Radiation Therapy With or Without Hydrogel Rectal Spacer.

Abstract

After prostate radiation therapy (RT), bowel, urinary, and sexual side effects and quality of life (QOL) declines are common. Phase 3 trials of rectal spacers (RSs) using ≥20 fractions found clinical and dose benefits and reduced QOL declines. However, the role of RS in stereotactic body radiation therapy (SBRT) is undefined. A prospective single-institution registry of prostate SBRT from 2012 to 2023 was analyzed by RS use (n = 290) versus no-RS (n = 1815). QOL scores were collected via Expanded Prostate Cancer Index Composite-26 at baseline and up to 5 years post-RT. Treatment used computed tomography and magnetic resonance imaging fusion and 3 to 6 fiducials for real-time tracking with Robotic SBRT (CyberKnife, Accuray Inc). Clinical target volume included prostate plus proximal seminal vesicles. Planning target volume margins were 5 mm except 3 mm posteriorly (35-36.25 Gy was delivered in 5 fractions). The primary endpoint was QOL trend over time by RS versus no-RS as evaluated by linear mixed-effects models that accounted for within-subject variability by controlling for key clinical and demographic characteristics. Clinically important change analyses were conducted using established minimally important difference (MID) thresholds to compare proportion of patients in each group with meaningful QOL declines at each timepoint. There were no differences in age, prostate specific antigen, or prostate volume between groups. RS was associated with more recent treatment (p < .001), intermediate- and high-risk disease (96% vs 85%; p < .001), androgen deprivation therapy use (52% vs 39%; p < .001), and Caucasian patients (63% vs 55%; p < .001). Baseline EPIC scores were similar. Declines in EPIC scores post-SBRT were small, approaching baseline after 6 months and remaining stable to 5 years. There were no clinically significant differences in QOL trend over time by RS vs no-RS. For the 2-month post-RT timepoint alone, the RS group had more favorable QOL with 1×MID and/or 2×MID thresholds met for urinary irritation, bowel, and vitality domains. No durable clinically significant QOL differences occurred between RS groups even in the baseline sexual domain EPIC ≥60/no androgen deprivation therapy subgroup. SBRT produced only modest, largely transient QOL declines that resolved by ∼6 months. RS did not confer a durable clinically meaningful QOL improvement; an isolated 2×MID signal at 2 months favored RS in select domains, but this was transient, and nondurable.