Dose-Escalated MR-Guided Radiotherapy for Localized Prostate Cancer

24 patients meeting inclusion criteria will be randomised between two arms. Arm 1 (Uniform dose) will receive 27 Gy in 2 fractions to the whole prostate + seminal vesicles (SV), the CTV, with 0 mm CTV-PTV margin. Arm 2 (De-escalated dose) will use two dose levels: The benign prostate (on MRI) will receive 20 Gy in 2 fractions with a 0mm PTV margin. The intraprostatic tumour mass(es) as seen on MRI will receive 27 Gy in 2 fractions. A 4mm GTV-PTV margin will be added to the MR visible tumour to form PTV 27Gy. The primary endpoint is emergent acute GU CTCAE v5 Grade 2+ toxicity, recorded within 3 months of completing radiotherapy. Secondary endpoints are CT CAE v5 acute GI toxicity, late toxicity, patient-reported outcome measures (PROMs) (EPIC-26, IPSS, and IIEF-5) at 4 and 12 weeks, 6 months, 1 and 2 years post treatment, PSA control and kinetics

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 (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)
• Short course (< 6 months) concurrent androgen deprivation therapy (antiandrogens or LHRH analogues) allowed though not mandated as per the discretion of the treating physician.
• 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.
• 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 Score > 19
• High grade disease (GG3) occult to MRI-defined lesion.
• Prostate volume >90cc
• Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
• Hip replacement, or other pelvic metalwork which causes significant artefact on diffusion-weighted imaging
• Previous pelvic radiotherapy
• Patients needing >6 months of ADT due to disease parameters, as per the discretion of the treating physician
• 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.