Phase 2 MR-guided SBRT uses MR-Linac image guidance (no drug; radiation dose de-escalation).

This Memorial Sloan Kettering Cancer Center–sponsored Phase 2 randomized trial (DESTINATION 2) tests whether intra-prostatic dose de-escalation can reduce urinary/bowel side effects while preserving tumor control in localized prostate adenocarcinoma. Both arms use MR-guided stereotactic body radiotherapy (SBRT) delivered on an MR-Linac in 2 fractions, leveraging daily MRI for alignment/adaptation and tighter margins than conventional CT-guided RT. The control arm treats the prostate more uniformly, while the investigational arm lowers dose to MRI-benign prostate tissue and maintains a high dose to MRI-visible, biopsy-proven tumor focus(es) (PIRADS 3–5 lesions that are boostable and <2.5 cm). Eligible patients include Grade Group 1–3 disease with PSA <20 ng/mL and largely T1–T2 (allowing up to radiologic T3a on MRI), without nodal or distant metastases; short-course ADT may be used when clinically appropriate (generally ≤6 months). Today’s care for Grade Group 1 often includes active surveillance, while many Grade Group 2–3 patients receive surgery or external-beam RT (often moderate hypofractionation or 5-fraction SBRT) ± short-course ADT; this study asks if MR-guided focal boosting plus de-intensifying uninvolved prostate can improve tolerability in an ultra-short 2-treatment regimen. Multiple New York sites (Middletown, Montvale, Commack, Harrison, Uniondale, Basking Ridge) | NCT07635238