Dose De-escalation in Prostate Radiotherapy Using the MRL (DESTINATION)

Inclusion Criteria: Men aged ≥18 years Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy Gleason score 3+3, 3+4 or 4+3 (Grade groups 1, 2 or 3) MRI stage T2 or less (as staged by AJCC TNM 2018) MRI-visible tumour(s) of Prostate Imaging-Reporting and Data System (PIRADS) v2 grade 3 or higher on T2 and diffusion-weighted imaging and/or dynamic contrast-enhanced imaging with concordant pathology Tumour nodule visible on MRI occupying <50% of prostate on any axial slice and <50% total prostate volume PSA <20 ng/ml prior to starting androgen deprivation therapy (ADT) Patients can be concurrently treated with androgen deprivation therapy if this would be standard of care. Luteinizing hormone-releasing hormone (LHRH) analogues or Bicalutamide are permitted. ADT is not mandatory where this would usually be omitted. World Health Organisation (WHO) Performance status 0-2 Ability of the participant understand and the willingness to sign a written informed consent form. Ability/willingness to comply with the patient reported outcome questionnaires schedule throughout the study. Exclusion Criteria: Contraindications to MRI (e.g. pacemaker, potentially mobile metal implant, claustrophobia) IPSS 19 or higher High grade disease (GG3) occult to MRI-defined lesion Post-void residual >100 mls, where known Prostate volume >90cc Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up Unilateral or bilateral total hip replacement, or other pelvic metalwork which causes artefact on diffusion-weighted imaging Previous pelvic radiotherapy Patients needing >6 months of ADT due to disease parameters. Previous invasive malignancy within the last 2 years excluding basal or squamous cell carcinomas of the skin, low risk non-muscle invasive bladder