Study: NCT05702619

Intervention type: DRUG
Intervention: Optional non-IMP pimonidazole
Description: patients will be asked to ingest an oral formulation of pimonidazole hydrochloride (HCl) (Oral HypoxyprobeTM-1). Pimonidazole HCl is a marker for hypoxia in tumour tissue when ingested as an encapsulated solid. Following oral administration, pimonidazole distributes throughout the body where it covalently binds to normal and tumour tissues that have regions of low oxygen concentrations (pO2 of ≤ 10 mmHg at 37oC). The tissue binding can be visualised by immunohistochemistry / light microscopy. The capsules are to be taken within 8-16 hours (optimal timepoint 12 hours) before the planned first biopsy within Arm 1 and before radical prostatectomy for patients in Arm 2. If the patient refuses the pimonidazole, forgets to take it, or if it is not available, the patient can still participate in the study and their samples will be stained for hypoxia post-biopsy.

Intervention type: DRUG
Intervention: Optional non-IMP pimonidazole
Description: patients will be asked to ingest an oral formulation of pimonidazole hydrochloride (HCl) (Oral HypoxyprobeTM-1). Pimonidazole HCl is a marker for hypoxia in tumour tissue when ingested as an encapsulated solid. Following oral administration, pimonidazole distributes throughout the body where it covalently binds to normal and tumour tissues that have regions of low oxygen concentrations (pO2 of ≤ 10 mmHg at 37oC). The tissue binding can be visualised by immunohistochemistry / light microscopy. The capsules are to be taken within 8-16 hours (optimal timepoint 12 hours) before the planned first biopsy within Arm 1 and before radical prostatectomy for patients in Arm 2. If the patient refuses the pimonidazole, forgets to take it, or if it is not available, the patient can still participate in the study and their samples will be stained for hypoxia post-biopsy.

Intervention type: DIAGNOSTIC_TEST
Intervention: CT-guided Bone Biopsy
Description: A CT-guided biopsy of a bone metastasis that is deemed to be easy to biopsy and in an area without major risk for pathological fracture or bleeding will be taken during the biopsy visit. Patients will receive routine local anaesthetic of the region to be biopsied followed by thorough disinfection of the biopsy site with antiseptic wipes. Patients will be asked to fast on the day of the procedure and to have an intravenous cannula inserted to allow the use of medication causing minimal sedation (for example midazolam and/or fentanyl) during the procedure if required to alleviate discomfort or pain.

Intervention type: DIAGNOSTIC_TEST
Intervention: TRUS-guided Targeted Transperineal Prostate Biopsy
Description: Transperineal Prostate Biopsy will be performed following standard clinical practice of local department. This will include pre-operative oral analgesia and prophylactic antibiotic treatment according to local hospital policy for transperineal prostate biopsies.

Intervention type: PROCEDURE
Intervention: Radical Prostatectomy
Description: Radical Prostatectomy will be performed according to standard of care robotic approach and as relayed to the patient by the attending urologic surgeon. The side effects of the surgery are the ones reported in the literature and the latest participant information leaflet provided prior patient consent (e.g. risk of erection disfunction, incontinence, etc.).

Intervention type: DIAGNOSTIC_TEST
Intervention: Whole-body MRI
Description: Whole-body MR imaging (wbMRI) will be performed once, before or after the biopsy study visit, depending on available examination slots in the Department of Radiology. WbMRI images will allow comparison of the numbers of bone metastases detected by routine bone scan and wbMRI for sensitivity assessment of both techniques for oligometastatic disease.

Intervention type: DIAGNOSTIC_TEST
Intervention: Prostate MRI scans
Description: Patients within Arm 2 will be offered the option to undergo additional MR imaging of the pelvis in addition to any standard of care imaging acquired. In patients who agree to undergo additional scans, MRI scans will be performed on 2 occasions prior to the radical prostatectomy. MRI scans will be acquired on either the MR sim diagnostic scanner, on the MR Linac scanner or on both.

Intervention type: OTHER
Intervention: Baseline bloods - for germline testing
Description: Arm 1 -~* 1-2 x 3.5mL blood samples collected into EDTA tubes for germ line DNA extraction and processing to PBMC for banking and future profiling of immune cell populations~* 1 x 10mL serum tubes for future, biobank related research projects, ie lipidomics, metabolics and microRNA analysis~ARM 2 -~A blood sample (maximum 20ml) will be taken for standard of care blood tests prior to prostatectomy including Full Blood Count, Renal Function and PSA. At the same time these standard of care bloods are taken, additional bloods - a maximum of 30ml - will be taken for research purposes as required for the following downstream analysis:~* Germ line DNA extraction and optional processing to PBMC for banking and future profiling of immune cell populations~* Biobank related research projects, ie lipidomics, metabolics and microRNA analysis

Intervention type: OTHER
Intervention: Baseline bloods - for germline testing
Description: Arm 1 -~* 1-2 x 3.5mL blood samples collected into EDTA tubes for germ line DNA extraction and processing to PBMC for banking and future profiling of immune cell populations~* 1 x 10mL serum tubes for future, biobank related research projects, ie lipidomics, metabolics and microRNA analysis~ARM 2 -~A blood sample (maximum 20ml) will be taken for standard of care blood tests prior to prostatectomy including Full Blood Count, Renal Function and PSA. At the same time these standard of care bloods are taken, additional bloods - a maximum of 30ml - will be taken for research purposes as required for the following downstream analysis:~* Germ line DNA extraction and optional processing to PBMC for banking and future profiling of immune cell populations~* Biobank related research projects, ie lipidomics, metabolics and microRNA analysis

Intervention type: OTHER
Intervention: Baseline bloods for CTCs and ct DNA taken at same time as baseline bloods in Arm 1
Description: 2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC) collection and circulating tumour DNA (ctDNA) extraction.

Intervention type: OTHER
Intervention: Post-pimonidazole bloods for CTCs and ctDNA
Description: ARM 1 - 2 x 10mL Streck cell-free DNA blood collection tubes® for circulating tumour cell (CTC) collection and circulating tumour DNA (ctDNA) extraction.