Is it all a MIRAGE?

Top Line: It’s 2022. Can we more precisely treat prostate cancer in a way that meaningfully diminishes toxicity?

The Study: In the single center, phase 3 MIRAGE trial, with initial reporting in abstract form at ASCO GU this month, 100 men undergoing stereotactic body radiation (SBRT) of 40 Gy in 5 fractions to the prostate for any risk disease were randomized to MR- versus CT-guidance during treatment. Let’s hold it right here and delve into what this really means. We’re all familiar with CT simulation MR fusion for planning and CT on-beam imaging for daily alignement. What MR-guidance means here is MRIs all the way through from MR simulation to real-time on-beam tracking with four MRIs generated per second(!) on the MRIdian linac with automatic treatment cessation if the prostate moved outside the PTV. Right, so very different treatment applications between arms. The crux of the anticipated difference in toxicity outcomes lies in the differing planning target volume (PTV) margins. Where the CT-guided arm received a somewhat standard 4 mm radial margin around prostate and seminal vesicles, this was reduced to an unprecedented 2 mm margin in the MR-guided arm. Kudos to the trial designers here because to find a significant difference on this scale, you gotta go small or go home. Fortunately prior proof of principle indicated such tight margins do not compromise coverage, particularly of the prostate—seminal vesicles demonstrated considerably more interfraction movement, particularly in relation to the prostate, leaving the door open to further advancements with the use of adaptive replanning. Now for the big reveal: the primary endpoint of acute (within 90 days) grade 2+ GU toxicity was halved in the MR-guidance arm (22%) versus the CT-guided arm (47%). What’s more, acute GI toxicity decreased from a rate of 14% with CT-guidance to 0% with MR-guidance. Finally, patient-reported GU and GI symptoms were significantly better in the MR-guidance arm at 1 month, but these returned to baseline in both arms and there was no difference by 3 months. Critics, ok cyberknife stakeholders, will point out that the toxicity benefit achieved is due entirely to very tight margins which can be achieved with technologies outside strictly the one presented here. Other critics may wonder whether these short-term toxicity improvements will translate to long-term improvements.

TBL: Reducing prostate SBRT margins to 2 mm using MRI planning and guidance more than halves acute GU and GI toxicity. | Kishan, ASCO GU 2022