The MIRAGE trial has demonstrated that MRI-guided stereotactic body radiotherapy (SBRT) significantly reduces both short-term and long-term toxicity in prostate cancer treatment compared to standard CT-guided SBRT. The study, led by Amar U. Kishan, MD, compared aggressive margin reduction using MRI-guidance with standard CT-guidance, showing a notable decrease in urinary and bowel toxicity.
Trial Design and Results
The MIRAGE trial (NCT04384770) was a randomized study comparing CT-guided SBRT to MRI-guided SBRT for prostate cancer. Patients in the CT-guided arm received SBRT with a 4mm margin, while the MRI-guided arm utilized a 2mm margin, leveraging the real-time imaging capabilities of MRI to precisely target the prostate while minimizing radiation exposure to surrounding tissues.
The primary endpoint, acute physician-reported urinary toxicity within 90 days, was significantly reduced in the MRI-guided arm. Specifically, grade 2 or greater acute genitourinary (GU) toxicity decreased from 43.4% in the CT-guided arm to 24.4% in the MRI-guided arm. Acute gastrointestinal (GI) toxicity also saw a significant reduction, dropping from 10.5% to 0% with MRI-guidance, as published in JAMA Oncology.
Long-Term Outcomes
Two-year follow-up data, presented in a subsequent manuscript, reinforced the benefits of MRI-guided SBRT. Physician-scored GU toxicity grade 2 or greater at 2 years was 51% with CT-guided SBRT and 27% with MRI-guided SBRT. Similarly, GI toxicity grade 2 or greater was 9.4% with CT-guided SBRT, reducing to 1.4% with MRI-guided SBRT.
Patient-reported outcomes also favored MRI-guided SBRT. The odds of experiencing a clinically significant decrease in bowel function (2x the minimal clinically important difference) were approximately 60% lower with MRI-guided radiation. Furthermore, among patients with evaluable sexual health scores, there was a 63% decreased odds of significant decline in sexual functioning with MRI-guided SBRT.
Implications for Clinical Practice
Dr. Kishan noted that the MIRAGE trial provides data supporting the reduction of margins from 4mm to 2mm, facilitated by MRI guidance, to decrease both short-term and long-term toxicity. This could lead to increased adoption of MRI-guided radiation. He also suggested that technological advancements might allow for similar margin reductions even with CT-guided SBRT.
"One implication would be if there is an uptake in MRI-guided radiation, that would allow a seamless move from larger margins to smaller margins," Dr. Kishan stated. "Thinking a little bit more broadly, perhaps there may be technological advances, even in the CT-guided, that allow us going from a 4 mm to 2 mm without MRI-guided; that's possible as well."
The trial also suggests a link between early and late toxicity, indicating that minimizing short-term toxicity can improve long-term patient quality of life. This challenges the notion that short-term toxicity is not meaningful because it eventually resolves.
Study Limitations
The MIRAGE trial was a single-center study conducted during the COVID-19 pandemic, which imposed limitations on patient questionnaires and follow-up. The primary endpoint focused on physician-scored toxicity due to practicality and the ability to assess it remotely. The trial was not powered to detect differences in long-term toxicity, but the two-year follow-up data provides valuable insights into the sustained benefits of MRI-guided SBRT.
Future Directions
While MRI-guided linear accelerators are currently less common and more expensive than CT-guided systems, the results of the MIRAGE trial may drive further research into margin reduction techniques for both MRI-guided and CT-guided SBRT. The ultimate goal is to improve patient outcomes and quality of life by minimizing treatment-related toxicity.
