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. 2023 Mar 1;9(3):365-373.
doi: 10.1001/jamaoncol.2022.6558.

Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial

Amar U Kishan  1   2 , Ting Martin Ma  1 , James M Lamb  1 , Maria Casado  1 , Holly Wilhalme  3 , Daniel A Low  1 , Ke Sheng  1 , Sahil Sharma  1 , Nicholas G Nickols  1   2 , Jonathan Pham  1 , Yingli Yang  1 , Yu Gao  1 , John Neylon  1 , Vincent Basehart  1 , Minsong Cao  1 , Michael L Steinberg  1
Affiliations

Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial

Amar U Kishan et al. JAMA Oncol. .

Abstract

Importance: Magnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial.

Objective: To determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance.

Design, setting, and participants: This phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up.

Interventions: Patients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions.

Main outcomes and measures: The primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes.

Results: Between May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month.

Conclusions and relevance: In this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist.

Trial registration: ClinicalTrials.gov Identifier: NCT04384770.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kishan reported receiving personal fees from ViewRay, Inc, Varian Medical Systems, and Boston Scientific; receiving speaking honoraria, consulting fees, and research support from Varian Medical Systems, ViewRay, Inc, and Intelligent Automation; receiving grants from Janssen and Point Biopharma; and receiving research funding from ViewRay, Inc, outside the submitted work and having equity in ViewRay, Inc. Dr Ma reported receiving personal fees from ViewRay, Inc, outside the submitted work. Dr Lamb reported receiving personal fees from ViewRay, Inc, outside the submitted work. Dr Low reported receiving personal fees from ViewRay, Inc, during the conduct of the study. Dr Nickols reported receiving grants from Janssen, Lantheus, and Bayer and receiving personal fees from OncoLinea outside the submitted work. Dr Yang reported receiving grants and consulting fees from ViewRay, Inc, outside the submitted work. Drs Gao, Neylon, and Cao reported receiving personal fees from ViewRay, Inc, outside the submitted work. Dr Steinberg reported receiving consulting fees from ViewRay, Inc, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram
CT indicates computed tomography; MRI, magnetic resonance imaging; SBRT, stereotactic body radiotherapy.
Figure 2.
Figure 2.. Rates of Acute Genitourinary (GU) and Gastrointestinal (GI) Toxic Effects
All toxic effects were scored based on the Common Terminology Criteria for Adverse Events, version 4.03 scale. CT indicates computed tomography; MRI, magnetic resonance imaging.
Figure 3.
Figure 3.. Short-term Changes in Patient-Reported Outcomes
A and C, Longitudinal changes in Expanded Prostate Cancer Index Composite-26 (EPIC-26) urinary incontinence and total bowel domain scores. P values were determined by the Mann-Whitney test. B and D, Thresholds were 15 or more points (increase) for International Prostate Symptom Score (IPSS) and 12 or more points (decrease) for EPIC-26 bowel domain scores. P values were determined by the χ2 test. CT indicates computed tomography; MRI, magnetic resonance imaging; SBRT, stereotactic body radiotherapy.
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References

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