Dose-Escalated MR-Guided Radiotherapy for Localized Prostate Cancer

DESTINATION 2 is a multi-centre randomised trial treating intermediate risk localised prostate cancer with 2 fraction Stereotactic Body Radiotherapy (SBRT). All radiotherapy will be delivered in two fractions (sessions) on an MR Linac using daily adaptation. Men will either receive uniform dose radiotherapy or de-escalated dose radiotherapy. The primary endpoint is acute GU CTCAE v5 grade 2+ toxicity. It will also look at late toxicity, patient-reported outcome measures and PSA control.

Inclusion Criteria: 1. Men aged ≥18 years 2. Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy 3. Gleason score 3+3, 3+4 or 4+3 (Grade groups (GG) 1, 2 or 3) 4. MRI stage T3a or less (as staged by AJCC TNM 2018). MRI must be performed within a year of randomisation 5. MRI-visible tumour(s) of PIRADS v2 grade 3 or higher and able to be delineated on T2 and diffusion-weighted imaging +/- dynamic contrast-enhanced imaging. Tumour nodule visible on MRI should be considered able to be boosted by treating clinician and \90cc 5. Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up 6. Hip replacement, or other pelvic metalwork which causes significant artefact on diffusion-weighted imaging 7. Previous pelvic radiotherapy 8. Patients needing \>6 months of ADT due to disease parameters, as per the discretion of the treating physician 9. Previous invasive malignancy within the last 2 years where this is likely to shorten lifespan the following will remain eligible: basal or squamous carcinomas of the skin, low risk non-muscle invasive bladder cancer (assuming cystoscopic follow up now negative) or small renal masses on surveillance.