A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT

Inclusion Criteria:

1. Aged ≥ 18 years at randomisation

2. Histopathological confirmation of prostate adenocarcinoma with Gleason/ISUP gradegroup scoring within twelve months of randomisation (unless otherwise discussed withthe CI or co-Clinical Leads)

3. Patients planned for 12-36 months androgen deprivation therapy

4. High risk localised prostate cancer as defined by

• Gleason 8-10 (grade groups 4 and 5) and/or

• Stage T3a/b or T4 and/or

• PSA > 20ng/ml (or >10 ng/ml for patients on 5-alpha reductase inhibitors)

5. Multi-parametric MRI of the pelvis- to include at least one functional MRI sequencein addition to T2W imaging within twelve months of randomisation

6. Radiological staging to exclude metastatic disease, prior to starting ADT, with oneof the following: PSMA PET-CT, fluciclovine/choline PET-CT, whole-body MRI, bonescan, CT of chest, abdomen and pelvis (imaging method as per local practice/standardof care).

7. WHO performance status 0-2

8. Ability of research subject to give written informed consent

Exclusion Criteria:

1. N1 or M1 disease

2. PSA >50ng/ml (or >25ng/ml for patients on 5-alpha reductase inhibitors), unlessPET-CT imaging has been performed to confirm N0M0 disease

3. Previous active treatment for prostate cancer

4. Patients where SBRT is contraindicated: prior pelvic radiotherapy, inflammatorybowel disease, significant lower urinary tract symptoms N.B. where patient hasrepeated imaging showing bowel in close apposition to target volumes that would makepelvic radiotherapy highly unlikely to be deliverable should be excluded.

5. Contraindications to fiducial marker insertion, where used- including clottingdisorders, or patients at high risk when stopping anticoagulation or antiplateletmedications

6. Bilateral hip prostheses or any other implants/hardware that would introducesubstantial CT artefacts and would make pelvic node planning more difficult.

7. Patients who have had chemotherapy within 6 weeks of the start of radiotherapy.

8. Life expectancy < 5 years