Phase 2 Microboost SBRT focal SIB (DNA damage via ionizing radiation) with whole-gland de-escalation

Georgetown University’s Phase 2 MIDAS trial tests whether MRI-defined “microboost” SBRT can safely intensify dose to up to 4 intraprostatic lesions (45 Gy in 5 fractions) while de-escalating dose to the remainder of the prostate to reduce toxicity. The intervention is external-beam stereotactic body radiation therapy, whose mechanism is ionizing radiation–induced DNA double-strand breaks leading to tumor cell death, delivered as a simultaneous integrated boost (SIB) to dominant MRI lesions with adaptive-risk whole-gland dosing. It is non-randomized, open-label, parallel-assignment, enrolling an estimated 58 men with NCCN low-risk (Arm 1: whole gland 30 Gy/5) or intermediate-risk disease (Arm 2: whole gland 35 Gy/5), with lesion selection driven by mpMRI (PI-RADS 4+ or selected PI-RADS 3 with GG2-3) and restrictions on higher-risk features (no GG4+, PSA ≤20, no T3a+). A key commercial/scientific angle is focal intensification plus whole-gland de-escalation in a curative setting—trying to preserve the disease-control benefits of lesion boosting while improving urinary/rectal tolerability over conventional full-dose whole-gland RT. Today’s care for low/intermediate-risk localized prostate cancer commonly includes active surveillance (selected low-risk), prostatectomy, or definitive radiation (moderate hypofractionation or 5-fraction SBRT) ± short-course ADT for higher-risk intermediate disease, and this study tests a more personalized intraprostatic dose-painting approach.