Optimal Prostate Study

To compare the toxicity, rate of local control, biochemical failure rate and quality of life of three different radiotherapy techniques (moderate hypofractionation, stereotactic body radiotherapy (SBRT) and standard radiotherapy plus 2 fractions of SBRT (BOOSTER)

Participants must have histologically proven prostate adenocarcinoma, good performance status and suitable for high dose radiotherapy. There are two groups of participants: Group 1: eligible participants will be randomised to have either moderate hypofractionation or standard radiotherapy plus SBRT (BOOSTER). Participants in this group must be able to have MRI, prostate fiducial markers (gold markers)and hydrogel insertion. Fiducial markers will be used to locate the prostate accurately during radiation treatment. Hydrogel is a temporary gel being injected into the space between the prostate and rectum to reduce the dose of radiation received by the rectum to minimise side effects from the treatment. Group 2: eligible participants will be randomised to have either moderate hypofractionation or SBRT. Participants will be reviewed for side effects. A Safety Committee will be formed containing multi-disciplinary team members. All serious adverse will be reported to the principal investigator and Human Research Ethics Committee within 24 hours.

Participants in this group will be randomised to either SBRT ( 36 to 45 GY in 5 fractions) or standard radiotherapy (60 Gy in 20 fractions). The allocation is 2 to 1. This means that two thirds of the participants on the trial will get the SBRT (5 treatments) and one third will get the standard fractions.

Participants in this group will be randomised to either standard radiotherapy plus SBRT (45 Gy in 20 fractions plus 20-30 Gy in 2 fractions-Booster) or standard radiotherapy (60 Gy in 20 fractions). The allocation is 2 to 1. This means that two thirds of the participants on the trial will get the Booster arm and one third will get the standard fractions.

Two thirds of the participants in this group will get the SBRT (5 treatments) and one third will get standard treatment (60 Gy in 20 treatments)

Two thirds of the participants in this group will get the two high precision radiotherapy plus 20 doses of standard external beam radiotherapy (ie the "Booster approach|") and one third will get the standard treatment (60 Gy in 20 treatments)

Markerless tracking algorithms will be assessed for accuracy against marker-based localisation by masking the markers and directly comparing the determined trajectories

Accuracy of various intrafraction guidance methods will be determined against triangulation of kilovoltage (kV) and Megavoltage (MV) projections

Inclusion criteria Histologically proven prostate adenocarcinoma PSA obtained within three months prior to enrolment ECOG performance status 0 to 2 Ability to understand and the willingness to sign a written consent Suitable for high dose irradiation to the prostate To be eligible for the arm containing Stereotactic Booster alone approach patient must have the following No contraindication to MRI such as pacemaker and severe claustrophobia Patient must be able to have fiducial markers placed in the prostate Patient must be able to have hydrogel insertion at the same time as fiducial markers Must have IPSS less than 15 Exclusion criteria Previous pelvic radiotherapy Prior total prostatectomy Unwilling or unable to give informed consent