This study will compare the safety and efficacy of curative radiotherapy to the prostate and lymph glands given in 5 visits to that of prostate alone radiotherapy given in 5 visits, in men with high risk localised prostate cancer.

This study will look at the safety of curative radiotherapy to the prostate and lymph glands given in 5 visits, in men with high risk localised prostate cancer.

The purpose of the research is to test an advanced type of external beam radiotherapy called stereotactic body radiotherapy (also known as SBRT) in 1128 participants with high risk localised prostate cancer (that is, prostate cancer that has not spread beyond the prostate gland but is at high risk of growing quickly or spreading). Importantly, this treatment delivers a potentially curative dose of radiotherapy in only 5 treatments over two weeks. Half the participants in the trial will receive radiotherapy to the prostate, the other half will have radiotherapy to the prostate as well as the surrounding lymph nodes. The investigators will follow patients in the trial for at least three and half years to see which treatment is best. The investigators will be looking at whether it is safe to give this treatment by reviewing any side-effects that occur and also assessing whether giving SBRT to the lymph nodes as well as the prostate reduces the chance of prostate cancer returning.

The treatment will take place at NHS radiotherapy centres that are experienced in giving SBRT and radiotherapy to the pelvic nodes, and have been quality assured to deliver these treatments

Inclusion Criteria:

1. Aged ≥ 18 years at randomisation

2. Histopathological confirmation of prostate adenocarcinoma with Gleason/ISUP grade group scoring within twelve months of randomisation (unless otherwise discussed with the 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 sequence in addition to T2W imaging within twelve months of randomisation

6. Radiological staging to exclude metastatic disease, prior to starting ADT, with one of the following: PSMA PET-CT, fluciclovine/choline PET-CT, whole-body MRI, bone scan, CT of chest, abdomen and pelvis (imaging method as per local practice/standard of 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), unless PET-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, inflammatory bowel disease, significant lower urinary tract symptoms N.B. where patient has repeated imaging showing bowel in close apposition to target volumes that would make pelvic radiotherapy highly unlikely to be deliverable should be excluded.
5. Contraindications to fiducial marker insertion, where used- including clotting disorders, or patients at high risk when stopping anticoagulation or antiplatelet medications
6. Bilateral hip prostheses or any other implants/hardware that would introduce substantial 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