MRI-guided vs. CT-guided SABR for prostate cancer: Results from the MIRAGE Phase III Clinical Trial

Research from the University of California has discovered that MRI-guided radiotherapy offers a ‘significant advantage’ over computed tomography (CT)-guided radiotherapy when used to treat patients with prostate cancer.

The first Phase III randomized clinical trial of its kind, the MIRAGE trial1 compared the two imaging modalities used for image-guided stereotactic ablative radiotherapy (SABR) for intact prostate cancer – CT imaging and MRI.

SABR is one of the most important advanced radiotherapy techniques currently available for treating tumours. This form of radiotherapy focuses beams of high-dose radiation at tumour sites with millimetric accuracy, with the aim of achieving local control in just a few short treatments.

This corresponds with the growing body of evidence that supports extreme hypofractionation2 – 5 fraction (5#) SABR for patients with low- to intermediate-risk (medium-risk) and selected high-risk localised prostate cancer.

Authored by Dr Amar Kishan at the University of California, Los Angeles, the Phase III MIRAGE trial highlighted the benefits of using MRI-guided treatment over CT-guided treatment in patients receiving the same radiation dose by SABR during prostate cancer treatment.

During the trial, 156 patients undergoing SABR for localised prostate cancer were randomly assigned to receive either CT-guided (on the TrueBeam or Novalis Tx) or MRI-guided treatment (on the MRIdian MR linac).

Planning margins of 4mm for the CT arm and 2mm for the MRI arm were positioned around the prostate and proximal seminal vesicles. A dose of 40 Gy was then delivered in 5#.

After 100 patients had reached 90 or more days since SABR had been first performed, a pre-specified interim futility analysis was conducted. Following this, a revised power calculation concluded that a conditional power of 89% could be maintained with a re-estimated sample size of 154 patients.

Therefore, despite originally aiming to recruit 300 patients, the MIRAGE trial was closed to accrual early.

For this trial, MR-based adaption was not used. Rectal spacers (44% received these across both arms) and elective nodal radiotherapy were also allowed at the physicians’ discretion.

The primary endpoint was measured as the incidence of acute (within 90 days of SABR) grade ≥2 genitourinary (GU) physician-reported toxicity.

Of the 154 patients (76 CT-arm; 78 MRI-arm) that were eligible for evaluation, the primary endpoint analysis showed that:

• Acute grade ≥2 GU toxicity was significantly reduced in men receiving MRI-guided SABR (19.0% absolute decrease: 43.4% vs. 24.4%, p = 0.01).
• Acute grade ≥2 gastrointestinal (GI) toxicity was also significantly reduced in men receiving MRI-guided SABR (10.5% absolute decrease: 10.5% vs. 0.0%, p = 0.003).
• The percentages of patients experiencing a clinically significant decrease in EPIC-26 urinary incontinence and bowel scores were significantly lower with MRI guidance at the 1-month time point (50.0% vs. 25.0%, p­ = 0.01). This means that men receiving MRI-guided SABR had less bowel upset and recovered more quickly.
• The percentages of patients experiencing a clinically significant increase in IPSS scores were significantly lower with MRI guidance at the 1-month time point (19.4% vs. 6.8%, p = 0.01). This suggests that patients receiving MRI-guided SABR had less toxicity and recovered more quickly.

The authors of this preliminary study theorised that the lack of statistical difference in patient-reported urinary and bowel function metrics at the three-month time point may be due to effective side effect management.

The MIRAGE trial builds on earlier evidence supporting MRIgRT for prostate cancer using the Phase II study led by Dr Anna Bruynzeel3. This Phase II study investigated early GI and GU toxicity after SABR using MRI guidance. Both clinician-reported and patient-reported outcomes were better than historical controls in this well-designed Phase II study.

Our Clinical Director of Urological Cancers, Dr Philip Camilleri, was delighted by the findings. He said:

“We are really excited with the outcomes of this study.

So far, we have treated more than 300 prostate patients at GenesisCare using MRI-guided SABR and have seen the impact it can have on improving patient quality of life first-hand. It’s fantastic to see that the MIRAGE trial provides further evidence to support this.” 

Our 5# SABR for prostate cancer service is an option available to patients which provides:

• A suitable alternative to surgery – this non-surgical treatment for prostate cancer is especially relevant for patients with co-morbidities in order to avoid a hospital stay or long waiting times.
• No increase in gastrointestinal or genitourinary side effects compared to 20 fractions.
• A reduction in treatment time and less interruption to the patient’s daily life.
• The additional benefit of a rectal spacer to help reduce damage to surrounding healthy tissues such as the bowel is offered at no extra cost.

GenesisCare is an established provider of specialist SABR treatment. A team of expert clinicians leads our service with extensive experience of this SABR modality for all tumour types, and they oversee a nationwide rapid access pathway.

We’re proud to be the first healthcare provider in the UK to introduce the MRIdian – an advanced MR linac.

The MRIdian combines a linear accelerator with a high-definition MRI scanner, allowing us to offer magnetic resonance image-guided stereotactic ablative radiotherapy (MRIgRT).

By capturing MR images of the target multiple times per second, the MRIdian provides real-time moving images that capture the anatomical positional changes that occur naturally within the body.

Uniquely, the MRIdian allows tracking of the target position in real-time, coupled with a gating facility that prevents beam delivery when the target is outside the treatment boundaries. This level of accuracy means that uncertainty is reduced, eliminating the need for large margins around the target; a functionality not included on other types of linacs.

MRI-guided radiotherapy improves conventional image-guided radiotherapy (IGRT) by providing improved soft tissue definition without additional radiation exposure through high-quality MR images. This world-class radiotherapy system is available at our centres in Oxford and Cromwell Hospital in London and can be accessed by patients throughout the UK.

The treatment planning system of the MRIdian is clear and intuitive, allowing clinicians to see as they treat – adjusting the beam to allow for movements and anatomical changes and making daily re-contouring of tumour and normal tissues straightforward.

The MRIdian uses a patented split-magnet MR design to prevent the radiation beam from being distorted by the magnetic field and ensure it remains at the optimum distance to deliver exceptionally sharp, high-dose-rate stereotactic ablative radiotherapy (SABR).

Find out more about MRI-guided radiotherapy, including case studies and how to refer.

For patients unsuitable for MRI-based imaging, conventional CT image-guided radiotherapy is offered across our network of centres in the UK with the inclusion of rectal spacers.

Rectal spacers are a game-changer in reducing the effects of toxicity to healthy tissues such as the bowel.

The spacer is inserted between the rectum and the prostate under local anaesthetic before radiotherapy treatment begins to temporarily move the anterior rectal wall further away from the prostate. This helps reduce the amount of radiation delivered to the rectum and limits toxicity, therefore reducing bowel, urinary and sexual function-related side effects.

If you wish to refer a patient for 5# SABR for primary prostate cancer on either a conventional linac or the MRIdian MR linac, the eligibility criteria are as follows:

• Biopsy-proven adenocarcinoma prostate, Gleason ≥ 6.
• T-Stage: T1c-T3b.
• No evidence of lymph nodes or distant metastases.
• Prostate volume ≤ 90 cc.
• IPSS ≤ 19.
• No TURP within eight weeks.
• No artificial hips (these are only suitable for treatment on the MR linac).
• No inflammatory bowel disease.
• IPSS ≤ 19
• No TURP within eight weeks
• No artificial hips (these are only suitable for treatment on the MR linac)
• No inflammatory bowel disease

If you have practicing privileges, please complete our comprehensive online referral form and we will process your referral immediately.

If you would like help with processing your referral or would like to discuss applying for practising privileges with GenesisCare, please email REM@genesiscare.co.uk

References

1. Kishan AU, Ma TM, Lamb JM, Casado M, Wilhalme H, Low DA, et al. Magnetic resonance imaging–guided vs Computed Tomography–guided stereotactic body radiotherapy for prostate cancer. JAMA Oncology. Jan 2023: doi: 10.1001/jamaoncol.2022.6558.
2. Tree A, Ostler P, van der Voet H, Chu W, et al. Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncololgy. Oct 2022: 23(10): 1308-1320.
3. Bruynzeel A, Tetar S, Oei S, Senan S, et al. A prospective single-arm phase II study of stereotactic magnetic-resonance-guided adaptive radiotherapy for prostate cancer: Early toxicity results. International Journal of Radiation Oncology Biology Physics. Dec 2019;105(5): 1086-1094.  van Moorselaar RJA, Lagerwaard FJ. A prospective single-arm phase II study of stereotactic magnetic-resonance-guided adaptive radiotherapy for prostate cancer: Early toxicity results. International Journal of Radiation Oncology Biology Physics. 2019;105(5):1086-1094.