Not just a MIRAGE: The benefit of MRI-guided radiotherapy for prostate cancer

Nearly 290,000 American men will be diagnosed with prostate cancer in 2023. The vast majority will be diagnosed with clinically localized disease. Active surveillance may be right for some, with others considering curative treatment options such as surgery or radiotherapy. Recent clinical trial data have cemented stereotactic body radiotherapy (SBRT), where high doses of radiation are delivered with high precision in generally five or fewer treatments, as a curative option for most men with localized prostate cancer. Because cure rates are so high, the major concern for patients with a new diagnosis of prostate cancer are the post-treatment side effects and impact to their quality of life. 

Side Effects and the “Margin Problem”

With respect to radiotherapy of any kind, including SBRT, the major side effects impacts can be categorized into one of three domains: urinary, bowel, and sexual.These domains can be impacted because the prostate is near the bladder, urethra, rectum, and neurovascular structures that are related to normal urinary, bowel, and sexual function. The goal is to treat the cancer with enough dose to kill it, while limiting the dose to the surrounding healthy organs. To account for motion, conventional radiation requires a margin, or additional boundary, to be placed around the prostate to ensure the cancer is targeted. The larger this margin, the higher the risk of side effects. If too small of a boundary is used, the cancer could be missed. For over a decade, the standard SBRT margins ranged from 4-5 mm, meaning the radiation dose would be intentionally delivered to cover not just the prostate, but a ring around the prostate measuring 4-5 mm in all directions.

MRIdian MRI-guided Radiation Therapy

MRIdian MRI-guided radiation therapy offers several theoretical advantages in the context of prostate SBRT, where high accuracy and precision are required.  First, MRIdian allows direct visualization of the prostate using an on-board MRI. This can help in aligning the treatment and bypasses the need to insert markers into the prostate. Second, it can monitor the position of the prostate with extremely high frequency (up to four times a second) and can automatically pause radiation delivery if the prostate moves out of a preset boundary. Together, these advantages ultimately allow for smaller margins while ensuring coverage of the prostate.

MIRAGE Trial

A logical question to ask is: if we can treat the prostate with tighter margins, would we improve outcomes for patients? Fortunately, we have the answer to this as a result of the MIRAGE trial. This was a single-center trial run at UCLA from May 2020 to October 2021, enrolling 156 patients. This trial was designed to evaluate whether acute moderate grade or greater genitourinary (GU) toxicity, or side effects, (i.e., grade ≥2) would be reduced as a result of treating with 2 millimeter (mm) margins (with the MRIdian) versus 4 mm margins (with a CT-based platform). As published earlier this year, the primary analysis demonstrates that aggressive margin reduction with MRI guidance accomplishes this goal. Specifically, reducing the margins from 4 mm with CT-guidance to 2 mm with MRI-guidance leads to significantly reduced physician-scored and patient-reported urinary and bowel toxicity. 

Why is the fact that this is a randomized trial important? It should be emphasized that randomized trials – which provide the highest level of evidence in support of medical interventions – are very rare, particularly in the context of new machines and technology. This is not the case with using an MRI-guided device to reduce margins – the MIRAGE trial provides evidence in the context of a randomized trial.

Based on the positive results of the MIRAGE trial, we have changed our practice to offer MRI-guided SBRT as our preferred institutional standard of care. We are excited to investigate further technological improvements, such as adaptive therapy, in future scientific studies and clinical trials.

Amar Kishan is an associate professor of radiation and urology at the University of California, Los Angeles. He also serves as the Vice Chair of Clinical and Translational Research within the department of radiation oncology. He is responsible for running a clinical service focused on treating patients with genitourinary malignancies, as well as leading a robust clinical and translational research program designed to improve post-treatment quality of life and treatment efficacy for patients with prostate cancer. He has received grant funding from the Department of Defense, the American Society for Radiation Oncology, the Prostate Cancer Foundation, the National Institutes of Health, and Kure-It. He has also received research support from ViewRay, Inc. (outside the scope of the MIRAGE trial), as well as honoraria from ViewRay, Inc.

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