MRI-Guided SBRT for Prostate Cancer?

WASHINGTON — MRI-guided stereotactic body radiotherapy (SBRT) showed sustained benefits over CT-guided SBRT for prostate cancer, in a study.

Amar Kishan, MD, of UCLA Health, presented the 2-year outcomes of the MIRAGE randomized clinical trial at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting.

The MIRAGE trial, which enrolled 156 patients between May 2020 and October 2021, aimed to evaluate whether aggressive margin reduction using MRI guidance could reduce toxicity and improve quality-of-life (QOL) outcomes after prostate SBRT. In his presentation, Kishan emphasized that the study population predominantly consisted of patients with unfavorable intermediate-, high-, or very high-risk disease (81%), reflecting a more aggressive disease profile than many previous SBRT trials.

Study Rationale and Endpoints

Kishan explained in his talk that planning target volume (PTV) accounts for possible uncertainties in beam alignment, patient positioning, organ motion, and organ deformity.

“In the context of prostate SBRT, the biggest ingredient in the PTV is organ motion,” he said.

The trial compared a standard 4-mm PTV margin for CT-guided SBRT to a reduced 2-mm margin for MRI-guided SBRT. This reduction was made possible by the advanced capabilities of MRI-guided radiotherapy, including highly precise real-time motion management, improved pretreatment alignment, and reduced contouring uncertainty.

The primary endpoint of the study, presented during last year’s ASTRO meeting, showed a significant reduction in acute grade ≥ 2 genitourinary (GU) toxicity from 43.4% with CT guidance to 24.4% with MRI guidance. The current presentation focused on 2-year outcomes, including patient-reported QOL measures and physician-scored toxicity.

In an interview, David Miyamoto, MD, PhD, of Massachusetts General Hospital, Boston, offered his opinion on the rationale of the MIRAGE trial. He described the study as “interesting,” noting that it examines the toxicity and patient-reported QOL outcomes for a relatively new radiation treatment technology, MRI-guided SBRT, in comparison with a more established technique, CT-guided SBRT.

He emphasized that SBRT is one of several equally effective treatment options for localized clinically significant prostate cancer, including moderately hypofractionated external beam radiotherapy, brachytherapy, and radical prostatectomy.

MRI-Guided SBRT Shows Reduced Toxicity

The cumulative incidence of grade ≥ 2 GU toxicity was significantly lower in the MRI-guided SBRT arm than in the CT-guided SBRT arm (27% vs 51%; P = .004). Similarly, grade ≥ 2 gastrointestinal (GI) toxicity was lower in the MRI-guided SBRT group than in the CT-guided SBRT group (1.4% vs 9%; P = .025).

To contextualize these findings, Kishan compared them with historical benchmarks. During his presentation, he noted that the cumulative incidence of grade ≥ 2 GU toxicity at 2 years in the CT-guided arm (51%) was higher than the 32.3% reported in the PACE-B trial, while the MRI-guided arm showed a marked improvement at 27%. Similarly, for GI toxicity, the CT-guided arm (9%) was comparable with the PACE-B benchmark of 12.5%, while the MRI-guided arm showed a reduction to 1.4%.

Miyamoto commented on differences between SBRT doses used in the MIRAGE and PACE-B trials.

“The SBRT dose of 40 Gy in five fractions to the PTV used in this study is relatively high compared to other SBRT regimens reported recently, such as the PACE-B trial, which prescribed 36.25 Gy to the PTV and 40 Gy to the CTV. It is promising to see that the use of MRI-guided SBRT resulted in lower rates of toxicity despite the use of this higher-dose regimen,” he said.

MRI-Guided SBRT Provides Improved QOL

Patients treated with MRI guidance experienced significantly lower rates of clinically relevant decrements (defined as two times the minimal clinically important difference) in urinary irritative symptoms (19.2% vs 35.3%; P = .03) and bowel function (4% vs 26%; P = .04), compared with those treated with CT guidance.

In addition, among patients who were not treated with androgen deprivation therapy, those who received MRI-guided SBRT had significantly lower rates of clinically relevant decrements in Sexual Health Inventory for Men scores than those who received CT-guided SBRT (22% vs 53%; P = .04).

Kishan emphasized the clinical significance of these findings, in an interview.

“Thankfully, men with prostate cancer diagnosed at a localized stage have an excellent prognosis. Therefore, when treating this type of disease, we need to be very mindful of toxicity, as men will hopefully live for years after treatment with any of the possible side effects,” he said.

The finding of reduced sexual health decrements at 2 years with MRI-guided SBRT among men not receiving androgen deprivation therapy was described by Miyamoto as “intriguing,” but requiring additional long-term follow-up to confirm whether this benefit persists over time.

Potential Implications for Clinical Practice

When asked about the potential impact of the MIRAGE trial findings on clinical practice, Kishan said, “The results of this trial highlight the importance of accurate targeting and precision during radiotherapy for prostate cancer.”

He added that the ability to pursue aggressive margin reduction relied upon the use of an MRI-guided linear accelerator, and the feasibility of adopting this technique at other centers would depend on their ability to achieve similar margin reductions through precise prostate motion tracking.

Miyamoto identified the availability of the treatment machine and the potentially higher costs of treatment as the two main barriers to widespread adoption of MRI-guided SBRT.

Looking Ahead

In his presentation, Kishan outlined the study’s strengths, which include its randomized design, the inclusion of patients with more aggressive disease profiles, and high compliance with QOL assessments (83% or higher at the 24-month timepoint). He noted, however, that the trial was conducted at a single institution with expertise in MRI-guided radiotherapy and that larger multicenter studies with long-term follow-up are needed to confirm the benefits of MRI-guided SBRT in patients with prostate cancer.

Miyamoto echoed the importance of longer-term follow-up.

The findings of this study “provide early support for the potential role of MRI-guided SBRT in reducing the side effects of radiotherapy, although longer-term follow-up is necessary to confirm that these benefits persist over time,” he said in an interview.

He added that it will be crucial to follow the patients long-term to determine whether there is any difference in prostate cancer disease control outcomes.

In an interview, Kishan identified several areas for future research.

“One of the exciting areas we will be looking into next is whether there will be further benefits derived from making a daily change to the radiation plan based off of daily anatomical variations, which is called adaptive radiotherapy. We will also explore if alternatives to MRI-guided radiotherapy can reliably provide tighter planning margins,” he said.

Kishan concluded by emphasizing that the findings of the MIRAGE trial suggest that the benefits of MRI-guided SBRT extend well beyond the acute phase posttreatment.

“When we think of precision medicine, we often think of molecularly targeted drugs; however, physical precision — leveraging the very advanced technologies we now have — is an important aspect of precision medicine as well,” he said, during the interview.

Kishan reported financial relationships with the University of California, Los Angeles (employment), Varian Medical Systems (honoraria); Varian Medical Systems, Boston Scientific, Novartis, Lantheus, Janssen(consulting fees); Janssen, Department of Defense, National Institutes of Health, Lantheus, POINT Biopharma, and ASTRO (research funding). Miyamoto reported financial relationships with Massachusetts General Hospital (employment) and Cardiff Oncology (research funding).