Pilot Study of Dose Escalation in Prostate Radiotherapy Using the MR-Linac (DESTINATION-MRL)

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 PIRADS v2 grade 3 or higher on T2 and diffusion-weighted imaging and/or dynamic contrast-enhanced imaging (multiparametric MRI or mpMRI) with concordant pathology
• Tumour nodule visible on MRI occupying \<50% of prostate on any axial slice and \<50% prostate volume
• PSA \<20 ng/ml prior to starting ADT (if applicable)
• Short course (\< 6 months) concurrent androgen deprivation therapy (antiandrogens or LHRH analogues) allowed though not mandated as per the discretion of the treating physician.
• 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 as per the discretion of the treating physician
• 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.