Acute toxicity and quality of life with stereotactic body radiotherapy versus conventional fractionated intensity-modulated radiotherapy to the prostate and pelvis in high-risk prostate cancer (SRAM): A randomized phase II trial.

Abstract

Stereotactic body radiotherapy (SBRT) to the prostate and pelvis in high-risk prostate cancer (HR-PC) may shorten treatment, but acute toxicity and quality-of-life (QoL) outcomes compared with conventional fractionated intensity-modulated radiotherapy (IMRT) remain uncertain. We report acute toxicity and early QoL outcomes from a randomized phase II trial. Between 2019 and 2024, 121 patients with node-negative HR-PC were randomized to SBRT (40 Gy in five weekly fractions to prostate, 36.25 Gy to seminal vesicles, 25 Gy to pelvis) or IMRT (76 Gy in 38 daily fractions: 50 Gy to prostate and pelvis, followed by 26 Gy prostate boost), with androgen deprivation therapy (18-24 months). The primary endpoint was acute grade ≥ 2 gastrointestinal (GI) or genitourinary (GU) toxicity occurring during radiotherapy or within 120 days after treatment completion (CTCAE v4.0). Secondary endpoints included patient-reported outcomes (Expanded Prostate Cancer Index Composite, International Prostate Symptom Score [IPSS]). Baseline characteristics were balanced (median age, 72 years; 49.6% prostate-specific antigen ≥ 20 ng/mL; 69% Gleason ≥ 8). Acute grade ≥ 2 GI toxicity occurred in 8.3% with SBRT versus 39.0% with IMRT (p < 0.0001); grade ≥ 2 GU toxicity in 23.3% versus 36.1%, respectively (p = 0.126). Grade 3 diarrhea occurred in one patient with IMRT; no grade ≥ 3 GU events were observed. At 1 month, bowel QoL declined more with IMRT (-10.4) than SBRT (-1.9; p = 0.0008), as did urinary domain decline (-11.3 vs -7.5). At 1 week, IPSS and QoL worsened less with SBRT than with IMRT (+4.55 vs +7.49, p = 0.062; QoL p = 0.029). Once-weekly SBRT to the prostate and pelvis significantly reduced acute GI toxicity and provided comparable GU safety relative to IMRT, with supportive early patient-reported outcomes. These findings extend SBRT evidence to the pelvis-inclusive setting in HR-PC and support phase III trials.