317 - Magnetic Resonance Imaging-Guided vs. Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: 2-Year Outcomes from the MIRAGE Randomized Clinical Trial

A. U. Kishan¹, J. M. Lamb¹, H. Wilhame², M. Casado¹, N. Chong¹, L. Zello¹, T. Jiang³, B. K. Neilsen⁴, Y. Yang⁵, J. P. Neylon⁶, D. Low¹, L. Valle¹, V. Basehart¹, T. M. Ma¹, M. Cao¹, and M. L. Steinberg¹; ¹Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, ²UCLA, Los Angeles, CA, ³University of California, Los Angeles, Los Angeles, CA, ⁴University of Nebraska Medical Center, Omaah, NE, ⁵Department of Radiation Oncology, University of California, Los Angeles, CA, ⁶Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA

Purpose/Objective(s): Aggressive margin reduction using magnetic resonance imaging (MRI) guidance has been shown to reduce acute grade =2 genitourinary (GU) and gastrointestinal (GI) toxicity following prostate stereotactic body radiotherapy (SBRT). Herein we report 2-year patient-reported quality of life outcomes and physician-scored toxicity from a phase III randomized trial comparing MRI-guided SBRT versus CT-guided SBRT. Materials/

Methods: Patients were randomized to receive SBRT with CT- vs. MRI-guidance (NCT XXXX). Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Pre-specified secondary endpoints included patient-reported Expanded Prostate Cancer Index Composite-26 (EPIC-26) scores and Sexual Health Inventory for Men scores, as well as the cumulative incidence of late grade =2 GU and GI toxicity. The proportion of patients experiencing a decrement in any given QOL domain exceeding 2x the minimal clinically important difference (MCID) threshold for the domain at any time point from 6-24 months was compared using the Chi-square test. The 2xMCID thresholds were 14 points for urinary irritative, 12 points for bowel, and 10 points for SHIM. Times to first Grade 2 GU or GI toxicity were estimated using the Kaplan-Meier method and the log-rank test was used to compare the treatment groups.
Results: Between May 2020 and October 2021, 156 patients (n=77 CT and n=79 MRI) were randomized. 81% of patients had NCCN unfavorable intermediate-, high, or very high-risk disease, 44% had placement of a spacer and 27% had nodal radiation. Patients treated with MRI-guidance had significantly lower rates of 2XMCID in the urinary irritative (19.2% vs. 35.3%, p=0.03) and bowel (26% vs. 4%, p=0.04) domains. Among patients not receiving androgen deprivation therapy, patients treated with MRI guidance had significantly lower rates of 2XMCID in SHIM scores (22% vs. 53%, p=0.04). Cumulative rates of both grade =2 GU and GI toxicity were lower in the MRI-guidance arm (GU, 27% [95%CI 41-63%] vs. 51% [41-63%], p=0.004 and GI, 1.4% [95%CI 0.2-9.6%] vs. 9% [4.6-19%], p=0.025 by log-rank comparing incidence functions).
Conclusion: Aggressive margin reduction with MRI-guidance significantly reduced urinary, bowel, and sexual QOL metric decrements as well late grade =2 GU and GI toxicity through 2-years of follow-up, maintaining benefits initially shown with acute toxicity. Longer-term follow-up will confirm whether these benefits persist and will allow comparison of oncological outcomes.