A prospective phase 1/2 nonrandomized clinical trial suggests that single-fraction stereotactic body radiotherapy may be a feasible and well-tolerated treatment strategy for carefully selected patients with localized prostate cancer.
The study, known as the ONE-SHOT trial, evaluated whether prostate SBRT could be safely and effectively delivered in just one fraction of 19 Gy. Standard prostate SBRT is most commonly delivered in 5 fractions, but there has been increasing interest in further reducing treatment duration while maintaining disease control and limiting toxicity.
Why This Study Matters
Ultrahypofractionated radiotherapy has become an established option for localized prostate cancer, with 5- to 7-fraction regimens supported by randomized phase 3 evidence.
The idea of reducing treatment to a single fraction is attractive for several reasons. It may improve patient convenience, reduce treatment visits, limit interfraction uncertainty from prostate motion and anatomical variation, and improve resource use in radiation oncology departments.
However, single high-dose prostate radiotherapy has remained controversial. Previous single-fraction HDR brachytherapy studies showed disappointing long-term disease control in some series, raising questions about whether one fraction is biologically and clinically enough.
The ONE-SHOT trial was designed to test this question using modern SBRT, urethra-sparing planning, real-time motion tracking, and prospective radiotherapy quality assurance.
Study Design
The trial was a multicenter, single-arm, prospective phase 1/2 study conducted across 5 academic centers in Europe and the United States.
It included 45 men with localized low- or intermediate-risk prostate cancer. Eligible patients had ISUP grade group 1 or 2 disease, PSA of 15 ng/mL or less, no significant transitional zone involvement, no extracapsular extension, prostate volume of 70 cc or less, and limited baseline urinary symptoms.
Among the 45 recruited patients, 43 were treated per protocol. The median age was 72 years.
Treatment Approach
All patients were treated with a single 19 Gy fraction of prostate SBRT.
Treatment was delivered using volumetric modulated arc therapy with flattening filter-free beams. Real-time image-guided radiotherapy was performed using the Calypso electromagnetic tracking system, with transponders implanted before simulation.
The clinical target volume included the whole prostate, with or without the proximal seminal vesicles depending on risk. A planning target volume margin of 5 mm was used, reduced to 3 mm posteriorly.
A key feature of the protocol was urethra sparing. The prescribed dose to the planning target volume was 19 Gy, while the urethral planning organ-at-risk volume was limited to 17 Gy.
All treatment plans underwent centralized prospective radiotherapy quality assurance before treatment.
Main Results
After a median follow-up of 55.3 months, the estimated 3-year biochemical relapse-free survival was 92.9%, meeting the study’s predefined primary endpoint.
The observed 5-year biochemical relapse-free survival was 88.0%, suggesting continued disease control, although longer follow-up is still needed.
PSA levels decreased from a mean of 6.8 ng/mL at baseline to 1.1 ng/mL at 18 months and 0.7 ng/mL at 3 years. A PSA bounce was observed in 51% of patients during follow-up, which is an important point for clinicians interpreting post-SBRT PSA kinetics.
Safety and Tolerability
Treatment was generally well tolerated.
At 3 years, grade 2 genitourinary adverse events were reported in 4 patients, or 9.8%. Grade 2 gastrointestinal adverse events were reported in 2 patients, or 4.9%.
Only one grade 3 event was reported, a case of proctitis at month 12.
Acute urinary symptoms were most common shortly after treatment, especially at day 5, and largely improved by week 12 and month 6. A second mild flare of urinary and gastrointestinal symptoms had been previously observed around 12 to 18 months, but by 3 years, gastrointestinal symptoms showed more pronounced recovery and genitourinary symptoms showed partial recovery.
Erectile dysfunction increased over time. Grade 2 or higher erectile dysfunction rose from 21.4% at baseline to 38.4% at 3 years, in a population with a median age of 72 years.
Quality of Life Findings
Quality-of-life outcomes supported the overall tolerability of the approach.
Using Expanded Prostate Cancer Index Composite scores, a significant minimally clinically important change was observed in 14% of patients for genitourinary scores and 28% for sexual scores.
The impact on gastrointestinal bother scores was minimal.
These findings suggest that single-fraction prostate SBRT can be delivered with limited bowel toxicity when strict planning constraints, urethral sparing, real-time motion control, and rigorous quality assurance are used.
How This Compares With Current Practice
Five-fraction SBRT remains the reference standard for localized prostate cancer.
The authors emphasize that comparisons between this single-fraction approach and standard 5-fraction regimens should be made cautiously, given the single-arm design, small sample size, and limited long-term follow-up.
Still, the toxicity profile appears broadly consistent with outcomes from established multifraction SBRT studies. The low rates of grade 2 or higher urinary and gastrointestinal toxicity may be related to several technical features of the trial, including urethra sparing, electromagnetic tracking, intrafraction motion control, and centralized prospective RTQA.
Limitations
The main limitations are the single-arm nonrandomized design, small cohort size, and inclusion of some patients with low-risk disease, which may limit generalizability.
The trial was powered for 3-year biochemical relapse-free survival, but this remains a surrogate endpoint. Longer follow-up beyond 5 years will be essential to confirm durable tumor control and better understand late toxicity.
The authors also note that the role of single-fraction SBRT should not yet be considered definitive. Larger studies and longer observation are needed before this approach can be positioned alongside standard 5-fraction SBRT.
Clinical Takeaway
The ONE-SHOT trial shows that single-fraction 19 Gy urethra-sparing prostate SBRT can achieve encouraging 3-year biochemical control with a favorable safety profile in carefully selected patients with localized low- or intermediate-risk prostate cancer.
The results support further investigation of one-fraction prostate SBRT as a potential curative treatment option.
For now, the message is promising but cautious: one treatment may be feasible, but longer follow-up and larger studies are needed before single-fraction SBRT can become a routine standard for localized prostate cancer.
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