A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0 M0 Prostate Cancer. ICORG 08-17

Primary Objective:

To determine if dose escalated IMRT for high risk localised prostate cancer can provide PSA relapse free survival similar to that reported by Memorial Sloan Kettering (Alicikus et al 2011).

Sub-Study 1 (Proteomic Analysis):

To use proteomic analysis of sequential blood and urine samples to detect changes in profiles that may predict outcome and identify prognostic biochemical markers of early disease progression and/ or toxicity. The unique molecular signatures may also allow the identification of targets for therapeutic intervention.

To undertake, where possible, other biochemical analyses including mRNA, miRNA and metabolite profiling.

Sub-Study 2 (Raman spectroscopic analysis):

To investigate a new approach to prediction of radiation response, based on biochemical fingerprinting

Secondary Objectives:

• Overall survival and disease-free survival rates.
• To evaluate the significance of published prognostic/ stratification factors such as the UCSF-CAPRA score and assess their application to the data from this study.
• To achieve the maximum dose escalation (up to 81Gy). This will be assessed as the percentage of patients that receive each dose level for all categories (dose increments of 1.8 Gy from 75.6 Gy up to max 81 Gy).
• The incidence and severity of acute and late GU, GI and erectile dysfunction toxicities will be described, and correlated with DVH parameters.

Inclusion criteria

• Patients undergoing a radical course of RT for high-risk disease (defined according to the National Comprehensive Cancer Network Practice Guidelines in Oncology v.1 as one or more of the NCCN high risk criteria > or equal to T3, > or equal to Gleason 8, PSA > 20ng/ml)
• Only patients requiring neo-adjuvant / adjuvant hormonal therapy will be included in this study
• Absence of distant metastases as demonstrated by history and physical examination, FBC, screening profile including liver function tests, PSA and bone scan
• All patients must have an MRI/CT of the prostate and pelvis to investigate the nodal status and precise T-stage. This MRI/CT scan must be performed prior to commencement of hormonal therapy. Suspicious nodes need to be histologically proven to be benign before the patient can be included in the study). M0 on staging.
• No previous surgery for urinary conditions except TURP or TRUS
• KPS > or equal to 60
• Age >18 years
• Provision of written informed consent in line with ICH-GCP guidelines

Exclusion criteria

• Previous RT to the pelvic region
• The patient has nodal involvement or it is decided to electively treat pelvic lymph nodes
• The patient has had a bilateral orchidectomy
• The patient has previously received a full course of hormonal treatment for his prostate cancer
• The patient has or has had other malignancies within the last 5 years (non-melanoma skin cancer is permitted)
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial or if it is felt by the research/ medical team that the patient may not be able to comply with the protocol
• Patients who have had a prostatectomy
• The presence of hip prostheses