MRI-Guided Radiotherapy Significantly Reduces Genitourinary, Gastrointestinal AEs in Prostate Cancer

Amar U. Kishan, MD

Patients who received MRI-guided stereotactic body radiotherapy (SBRT) for prostate cancer had fewer acute moderate physician-scored genitourinary and gastrointestinal toxic effects, and smaller decrements in patient-reported urinary and bowel function compared with those who received computed tomography (CT)-guided SBRT, according to findings from the phase 3 MIRAGE trial (NCT04384770).

Lead author Amar U. Kishan, MD, and investigators at the University of California, Los Angeles (UCLA) conducted a prespecified interim analysis on October 1, 2021, after 100 patients (51 in the CT arm and 49 in the MRI arm) were evaluable for the primary end point, incidence of acute (≤90 days after SBRT) grade 2 or greater genitourinary toxic effects. MRI-guided SBRT delivered using the MRIdian LINAC was associated with an absolute reduction of 19.0% for acute grade 2 or higher genitourinary toxic effects and 10.5% for gastrointestinal effects. Furthermore, there were no grade 3 genitourinary toxic effects or grade 2 or greater gastrointestinal toxic events in the MRI arm.

“With prostate cancer, we know that cure rates are very high,” Kishan, vice chair of Clinical and Translational Research and chief of the Genitourinary Oncology Service for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center, said in an interview with OncLive^®.

“One of the primary focuses of research interests globally, and within my institution as well, is to try to reduce the side effects of the treatment. People are living a long time after their diagnosis and treatment, which is great, but we want to make sure they're living without toxicity. Steps like this, reducing the margins with a more accurate treatment to try to drop toxicity, I think are steps in the right direction.”

Kishan said that the prostate does not show up clearly on traditional CT scan or X-ray, and the organ can shift, so physicians have traditionally used metallic markers to track the prostate as it moves. To account for that imprecision, physicians treat a 4 mm margin around the tumor. However, that also means healthy tissues receive radiation, which can cause adverse effects.

He added that MRI provides better anatomical detail of the prostate in real time, allowing physicians to use a smaller margin and spare healthy tissue.

“When you're treating prostate cancer with any form of external radiation, you need to account for the fact that there are some uncertainties and radiation delivery,” he said. “We always design radiation plans to precisely target the prostate, but we need to account for the fact that the prostate is a moving target, and it sometimes isn’t easily imaged on CT or X ray.”

Until recently, physicians weren’t able to use a linear accelerator (LINACs) within an MRI machine because of magnetic interference. Now, with MRI-guided LINACs, they can deliver treatment while the patient is inside the MRI bore and get a more accurate picture of the organ.

“Maybe most importantly, [the MRI-guided LINAC] has what’s called a ‘cine’ MRI that is getting an MRI image 4 times per second and stitching that together to make kind of a real time monitoring of the prostate,” Kishan said. “If the prostate moves too much, the beam will actually automatically turn off. That allows us to be confident that we can hit the prostate but not need a 4 mm margin, but rather a 2 mm margin.”

Investigators assigned patients with histologically confirmed, clinically localized prostate adenocarcinoma to CT-guided SBRT (n = 77) or MRI-guided SBRT (n = 79). Investigators found that the incidence of acute grade 2 or greater genitourinary toxic effects was significantly lower with MRI (24.4%; 95% CI, 15.4%-35.4%) vs CT (43.4%; 95% CI, 32.1%-55.3%; P = .01). The same was true for 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), respectively.

Kishan et al enrolled 156 adult men treated at UCLA into this nonblinded, single-center, phase 3 randomized clinical trial from May 2020 to October 2021. All patients were assigned to SBRT using a computer-generated randomization list with permuted blocks of 6. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions. Investigators stratified randomization by the baseline International Prostate Symptom Score (IPSS; ≤15 or >15) and prostate gland volume (≤50 cc or >50 cc) as determined by a diagnostic MRI.

The median patient age the CT arm was 71 years (interquartile range [IQR], 67-77) and 79 years (IQR, 68-75) in the MRI arm.

Overall, 29 (19%) patients had favorable risk disease, 69 (44%) had placement of a rectal hydrogel spacer, 37 (24%) received nodal radiation, 41 (26%) received a simultaneous integrated boost to the dominant lesion, and 106 (68%) received hormonal therapy. There were no significant differences between arms for any of these parameters.

Secondary outcomes included acute gastrointestinal grade 2 or greater toxicities and changes in IPSS and Expanded Prostate Cancer Index Composite-26 (EPIC-26). Clinically relevant decrement in EPIC-26 domains was defined as greater than 18 points for the urinary incontinence, 14 for urinary irritative or obstructive, 12 for bowel, and 24 for sexual domains. Investigators determined that a 15-point or greater increase in IPSS was clinically relevant.

MRI guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8%) vs 19.4% for CT-guided SBRT (P = .01). MRI also significantly reduced percentage of patients with a clinically significant decrease in EPIC-26 bowel scores, 25.0% vs 50.0%; P = .001) at 1 month. However, the differences were not significant at 3 months (1.4% vs 4.1%, respectively; P = .30)

The percentages of patients experiencing a clinically significant decrease in EPIC-26 urinary incontinence and a large increase in IPSS were significantly lower with MRI guidance at 1 month. The same was true for patients a clinically significant decrement in EPIC-26 bowel scores. Investigators hypothesized that the toxicity benefits were most like due to the significantly reduced planning target volume margins achieved with MRI.

Reference

Kishan AU, Ma TM, Lamb JM, et al. Magnetic resonance imaging–guided vs computed tomography–guided stereotactic body radiotherapy for prostate cancer: the MIRAGE randomized clinical trial. JAMA Oncol. Published online January 12, 2023. doi:10.1001/jamaoncol.2022.6558