Online adaptive magnetic resonance-guided stereotactic body radiotherapy was associated with low rates of clinically significant toxicity and limited deterioration in quality of life among patients with localized prostate cancer, according to findings from a prospective study published in Clinical and Translational Radiation Oncology.
The study included 108 patients treated with online adaptive MR-guided stereotactic body radiotherapy (SBRT). At three months, grade 2 or higher genitourinary toxicity was reported in 3% of patients, while no grade 2 or higher gastrointestinal toxicity was observed. These rates remained low at six months.
Daily adaptive treatment was delivered with 2-mm margins and without the routine use of hydrogel rectal spacers or fiducial markers. No biochemical failures were recorded during 12 months of follow-up.
Can Daily Adaptation Make Prostate SBRT Safer?
SBRT is an established treatment option for localized prostate cancer. By delivering larger radiation doses over fewer sessions, it can shorten treatment duration while maintaining disease control comparable with conventionally fractionated or moderately hypofractionated radiotherapy.
However, prostate SBRT is technically demanding. The prostate can move both between and during treatment sessions, while changes in bladder and rectal filling can alter the position of the target and nearby organs. These challenges are particularly important because the prostate lies close to the rectum, bladder, and urethra.
Magnetic resonance-guided radiotherapy provides enhanced visualization of soft tissues, continuous motion monitoring, intrafraction gating, and the ability to modify the treatment plan according to the patient’s anatomy on each treatment day.
The prospective, single-center, non-randomized study led by Abrahams Ocanto and colleagues evaluated the feasibility, early safety, patient-reported outcomes, and short-term biochemical response of a fully online adaptive MR-guided SBRT approach.
Five Fractions Guided by the Anatomy of the Day
The study included consecutive men aged 18 years or older with histologically confirmed, non-metastatic prostate adenocarcinoma. Patients were treated between July 1, 2023, and July 1, 2025.
The median age was 74 years. Most patients had intermediate-risk disease, including 33% with favorable intermediate-risk and 29% with unfavorable intermediate-risk prostate cancer. Low-risk disease was reported in 24%, while 14% had high-risk disease. One patient had clinically node-positive pelvic disease without distant metastases.
Androgen deprivation therapy was administered to 38 patients, representing 35% of the study population.
All patients received treatment using a 0.35-T MR-Linac system. The prescribed dose was:
- 36.25 Gy in five fractions for low-risk disease
- 36.25–40 Gy in five fractions for intermediate-risk disease
- 40 Gy in five fractions for high- and very high-risk disease
Selected patients could also receive elective pelvic nodal irradiation of up to 25 Gy in five fractions, with a simultaneous integrated boost of up to 35 Gy to radiologically involved pelvic lymph nodes.
A uniform 2-mm expansion was used to create the prostate planning target volume. Treatment fractions were delivered on alternate days.
Before every fraction, a new MRI scan was obtained and the treatment plan was adapted to the patient’s anatomy that day. Continuous cine MRI was then acquired at four frames per second during radiation delivery. The beam was automatically interrupted when more than 5% of the prostate volume moved outside the predefined 2-mm gating boundary.
Fiducial markers and rectal spacers were not routinely used.
Genitourinary Symptoms Declined Rapidly After Treatment
At two weeks after treatment completion, grade 2 or higher genitourinary adverse events were observed in 22% of patients. By three months, this rate had fallen to 3% and remained at 3% at six months.
Grade 2 or higher gastrointestinal adverse events were reported in 1% of patients at two weeks. No grade 2 or higher gastrointestinal events were recorded at three or six months.
No grade 3 gastrointestinal adverse events occurred. One grade 3 genitourinary event, involving urinary retention, was observed at 12 months.
Any-grade genitourinary, gastrointestinal, and sexual adverse events were reported in 32%, 2%, and 8% of evaluable patients at three months. At six months, these rates had decreased to 9%, 1%, and 1%, respectively.
Overall, physician-reported adverse events were predominantly mild, transient, and improved over time.
Baseline Urinary Symptoms Identified a Higher-Risk Group
The investigators examined whether baseline clinical characteristics were associated with grade 2 or higher acute genitourinary toxicity.
A higher baseline International Prostate Symptom Score was associated with an increased risk of clinically significant genitourinary adverse events in the univariable analysis, with an odds ratio of 1.108.
The association remained significant after multivariable adjustment, with an odds ratio of 1.09.
Patients with prostate volumes greater than 50 cc had significantly larger planning target volumes. However, prostate volume was not independently associated with grade 2 or higher genitourinary adverse events. No correlation was identified between the radiation dose level and toxicity.
These findings suggest that baseline urinary symptom burden may be more informative than prostate size when evaluating the risk of early urinary toxicity.
Quality of Life Was Largely Preserved
Patient-reported outcomes were evaluated using the International Prostate Symptom Score, the Expanded Prostate Cancer Index Composite-26, and the EORTC QLQ-C30 questionnaire.
At six months, urinary symptom scores remained stable in 61% of evaluable patients. Minor changes were reported by 30%, while 9% experienced clinically relevant worsening.
Within the EPIC-26 urinary incontinence domain, scores remained stable in 79% of patients, while 21% reported mild worsening.
For urinary irritative or obstructive symptoms, 58% remained stable, 21% experienced mild worsening, and 21% experienced clinically relevant deterioration.
Bowel function remained stable in 75% of patients. Mild worsening was reported in 12.5%, while another 12.5% experienced clinically relevant deterioration.
In the sexual domain, 42% of patients remained stable, while the remaining patients reported either mild or clinically relevant worsening. The investigators noted that these results require cautious interpretation because 35% of participants received androgen deprivation therapy, which can independently affect sexual function.
Global quality of life also remained largely preserved. At six months, 53% of patients reported no relevant change and 47% reported mild changes.
Overall, no statistically significant difference was found between baseline and six-month patient-reported evaluations.
PSA Levels Continued to Fall During Follow-Up
The median prostate-specific antigen level was 8.56 ng/mL at diagnosis.
Median PSA subsequently decreased to:
- 1.37 ng/mL at three months
- 1.03 ng/mL at six months
- 0.76 ng/mL at 12 months
No biochemical failures were observed during the first year of follow-up.
While these early biochemical results are encouraging, the investigators emphasized that longer follow-up is required for a disease with a prolonged natural history.
Does Online Adaptation Add More Than Smaller Margins?
The phase III MIRAGE trial previously demonstrated lower rates of acute grade 2 or higher genitourinary and gastrointestinal toxicity with MR-guided SBRT compared with CT-guided SBRT. The benefit was largely attributed to the reduction of planning target volume margins from 4 mm to 2 mm, enabled by improved visualization and motion management.
However, MIRAGE did not incorporate daily online adaptive replanning.
In the current study, every patient was treated using a fully adaptive workflow with 2-mm margins. Despite the absence of routinely used rectal spacers, clinically significant gastrointestinal toxicity remained uncommon.
The authors cautioned against direct comparisons between separate studies. Nevertheless, the findings suggest that daily online adaptation may further optimize rectal sparing and could potentially reduce reliance on rectal displacement strategies in selected patients.
Prospective comparative research will be needed to determine whether online adaptation provides a clinical advantage beyond improved imaging, motion monitoring, and margin reduction alone.
Important Questions Remain Beyond the First Year
Several limitations were acknowledged.
The study was conducted at a single center and did not include a randomized comparison group, limiting the ability to establish whether the adaptive approach is superior to other image-guided strategies.
Follow-up was also relatively short. Late urinary and rectal complications can develop beyond the first year and therefore cannot yet be fully assessed.
Completion of patient-reported outcome questionnaires declined over time, potentially introducing response bias. Treatment dose and the use of androgen deprivation therapy were also individualized according to routine clinical practice, creating some heterogeneity within the cohort.
Despite these limitations, the prospective design, systematic documentation of physician-reported adverse events, and use of validated quality-of-life instruments strengthen the clinical relevance of the findings.
A Promising Early Safety Profile
Online adaptive MR-guided SBRT demonstrated a favorable early safety profile in patients with localized prostate cancer.
Clinically significant genitourinary toxicity declined substantially after the first weeks of treatment, gastrointestinal toxicity remained uncommon, and urinary, bowel, and global quality of life were largely preserved.
The ability to adapt treatment to daily anatomy, monitor prostate motion continuously, and interrupt radiation delivery when the target moves outside a narrow boundary offers a highly precise approach to five-fraction prostate radiotherapy.
Longer follow-up and comparative studies are now needed to establish whether daily online adaptation can improve long-term toxicity, quality of life, and oncological outcomes beyond the benefits already achieved through MR guidance and smaller treatment margins.
Written by Nare Hovhannisyan, MD
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