Stereotactic body radiotherapy (SBRT), most commonly delivered in 5 fractions, is an established treatment option for patients with localized prostate cancer. While efforts to further reduce treatment to fewer than 5 fractions are ongoing, the efficacy and tolerability of single high-dose SBRT remain to be established.
To determine in men with localized prostate cancer whether a single-fraction SBRT can be a valid treatment option in terms of biochemical disease control and safety.
This multicenter, single-arm, prospective, phase 1/2 nonrandomized clinical trial included men with localized prostate cancer at low or intermediate risk, with International Society of Urological Pathology grade group 1 or 2, and without significant tumor in the transitional zone. Participants were recruited between 2017 and 2022 in 5 academic centers in Europe and the US. Data were analyzed between February and May 2026.
Participants were treated with a 19-Gy single-fraction prostate SBRT with urethra-sparing and intrafraction motion control.
The primary end point was biochemical relapse-free survival (bRFS) at 3 years (expected value of 96% included in the 95% CI). Secondary end points included occurrence of genitourinary (GU), gastrointestinal (GI), and sexual adverse events (AEs) and quality of life (QOL) assessment.
Among the 45 patients recruited (median age, 72 [range, 60-82] years), 43 were treated per protocol. After a median follow-up of 55.3 (IQR, 49.9-60.7) months, the estimated 3-year bRFS was 92.9% (95% CI, 85.4%-100%), meeting the primary end point. At 3 years, grade 2 GU and GI AEs were observed in 4 (9.8%) and 2 (4.9%) participants, respectively, with only a grade-3 proctitis observed in 1 patient at month 12. Grade 2 or higher erectile dysfunction increased from 9 of 42 patients (21.4%) at baseline to 15 of 39 (38.4%) at 3 years. A significant minimally clinically important change in Expanded Prostate Cancer Index Composite scores was observed in 6 (14%) and 12 (28%) participants for GU and sexual scores, respectively. The impact in GI bother scores was minimal.
In this multicenter phase 1/2 trial, a single-fraction 19-Gy urethra-sparing SBRT met the primary end point, achieving a 3-year bRFS of 92.9%, with grade 2 GU and GI AEs remaining below 10% and 5%, respectively, at 3 years. Longer follow-up is warranted to assess long-term disease control.
ClinicalTrials.gov Identifier: NCT03294889.
JAMA oncology. 2026 Jun 18 [Epub ahead of print]
Thomas Zilli, Ciro Franzese, Matthias Guckenberger, Niccolò Giaj-Levra, Nicolas Mach, Verane Achard, Nicolas Vial, Andrew McDonald, Filippo Alongi, Marta Scorsetti, Guillaume Constantin, Aurelie Bertaut, Raymond Miralbell
Radiation Oncology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy., Department of Radiation Oncology, University Hospital Zürich, University of Zürich, Zürich, Switzerland., Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don-Calabria, Negrar, Italy., Faculty of Medicine, Geneva University, Geneva, Switzerland., Radiation Oncology, University of Alabama at Birmingham O'Neal Comprehensive Cancer Center, Birmingham, Alabama., Methodology and biostatistics unit, Centre Georges François Leclerc, Dijon, France.