Dose De-escalation in Prostate Radiotherapy Using an MR-Linac in Two Fractions

Inclusion criteria

• Men aged ≥18 years
• Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy
• Gleason score 3+3, 3+4 or 4+3 (ISUP Grade groups (GG) 1, 2 or 3)
• 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. MRI must be performed within 3 months of trial entry
• The MRI-defined lesion must be confirmed as malignant on biopsies (any Gleason grade is sufficient as long as Gleason score is reported).
• MRI stages mT1 and T2 or mT3a with ≤ 1mm tumour outside gland AND otherwise favourable intermediate risk characteristics (Gleason 3+3, 3+4)(as staged by AJCC TNM 2018)
• PSA <20 ng/ml prior to starting androgen deprivation therapy (ADT).
• WHO Performance status 0-2
• Ability of the participant to understand and the willingness to sign a written informed consent (IC) 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. As a guide, any pathology for which you would consider surveillance is allowed outside of the MRI-defined area.
• 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 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 cancer (assuming cystoscopic follow up now negative) or small renal masses on surveillance.