High dose radiotherapy is a very effective treatment for prostate cancer. However, there is an increased risk of side effects compared to lower dose radiotherapy. This study will investigate the use of dose painting radiotherapy. Dose painting radiotherapy administers a high dose of radiotherapy to areas of cancer inside the prostate and a lower (standard) dose to the rest of the prostate. This may improve control of the cancer without increasing the side effects. The radiotherapy is given in 20 doses, called fractions.

For patients with prostate cancer which has not spread, the typical treatment is hormone therapy and radiotherapy.

It is possible to identify areas within the prostate which contain a significant amount of cancer with functional MRI or with 18F choline PET CT scans. These areas are called Dominant Intraprostastic Lesions 'DILs'. Targeted prostate biopsies help to confirm scan results. The radiotherapy dose to the DILs is increased, whilst the rest of the prostate is treated with the standard dose. This technique is called dose painting or 'boost' Intensity Modulated Radiotherapy Treatment (IMRT).

IMRT is given in 37 treatment doses called fractions, once a day for about 8 weeks. A hypofractionated schedule is the administration of the total radiotherapy treatment over a smaller number of fractions, at a higher dose per fraction. Recent evidence suggests that the idea of using a 'hypofractionated' treatment schedule is better and more convenient with a similar number of side effects as a regular schedule.

In the study, 50 patients with intermediate/high risk prostate cancer suitable and fit for radical radiotherapy will be recruited. The patients undergo a staging functional MRI scan, fiducial marker insertion (required for image guided radiotherapy) and hormone therapy as per standard of care treatment. The choline PET CT scan and targeted prostate biopsies are optional. They are useful if the MRI is difficult to interpret and will be offered to patients if they are felt to be appropriate by the clinician. After 2 months hormone therapy (standard protocol) patients have a CT /MRI planning scan and undergo IMRT with 20 treatments (fractions).The patient will then be followed up until 24 months after they started radiotherapy treatment.

The main aim is to assess the side effects related to the bladder and bowel at 18 weeks (acute toxicity) after starting hypofractionated IMRT.

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the prostate

2. NCCN intermediate/high risk disease and estimated risk of lymph node involvement 15 - 40%*

3. MRI stage T2a-T4 N0M0

4. Age 18-80 years

5. Normal blood count (Hb >11g/dl, WBC > 4000/mm3, platelets >100,000/mm3)

6. WHO performance status 0 or 1

7. Fully informed written consent

   • Risk of pelvic lymph node involvement = (Gleason score - 6) x 10 + 2/3 PSA

Exclusion Criteria:

1. Prior radiotherapy to the prostate or pelvis
2. Prior hormone therapy or radical prostatectomy
3. Total hip replacement
4. Clinically significant inflammatory bowel disease
5. Contraindication to have diagnostic MRI scans
6. Unable to have a general anaesthetic
7. Anti-coagulant therapy which cannot be temporarily stopped