Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions

Prior treatment

• Contraindications to MRI (e.g. pacemaker, potentially mobile metal implant, claustrophobia)
• Previous pelvic radiotherapy

Other illness

• High grade disease (GG3) occult to MRI-defined lesion. As a guide, any pathology for which you would consider surveillance (eg GG1, low volume GG2) is allowed outside of the MRI-defined area.
• Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
• Patients needing \>6 months of ADT due to disease parameters.
• 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.
• Participating in another interventional trial for prostate cancer

Other

• Severe GU symptoms that would preclude extreme hypofractionation per the discretion of the treating physician.
• IPSS Score \> 19
• Prostate volume \>90cc
• Hip replacement, or other pelvic metalwork which causes significant artefact on diffusion-weighted imaging

• Men aged ≥18 years
• Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy
• Gleason score 3+3, 3+4 or 4+3 (Grade groups (GG) 1, 2 or 3)
• MRI stage T3a or less (as staged by AJCC TNM 2018). MRI must be performed within a year of randomisation
• 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 \<2.5cm in maximal dimension
• The MRI-defined lesion must be confirmed as malignant on biopsies (Gleason grade must be within the limits expressed in inclusion factor 3)
• Patients can be concurrently treated with androgen deprivation therapy (ADT) if this would be standard of care. LHRH analogues, LHRH agonists or Bicalutamide are permitted. ADT is not mandatory where this would usually be omitted.
• PSA \<20 ng/ml prior to starting ADT, if used
• WHO Performance status 0-2
• Ability of the participant understand and the willingness to sign a written informed consent form.
• Willing to consent to contraception during and for 1 year after treatment when applicable.
• Ability/willingness to comply with the patient reported outcome questionnaires schedule throughout the study.