title: INNOVATE: A prospective cohort study combining serum and urinary biomarkers with novel diffusion-weighted magnetic resonance imaging for the prediction and characterization of prostate cancer.
abstract: Whilst multi-parametric magnetic resonance imaging (mp-MRI) has been a significant advance in the diagnosis of prostate cancer, scanning all patients with elevated prostate specific antigen (PSA) levels is considered too costly for widespread National Health Service (NHS) use, as the predictive value of PSA levels for significant disease is poor. Despite the fact that novel blood and urine tests are available which may predict aggressive disease better than PSA, they are not routinely employed due to a lack of clinical validity studies. Furthermore approximately 40 % of mp-MRI studies are reported as indeterminate, which can lead to repeat examinations or unnecessary biopsy with associated patient anxiety, discomfort, risk and additional costs.
  
  
  
  We aim to clinically validate a panel of minimally invasive promising blood and urine biomarkers, to better select patients that will benefit from a multiparametric prostate MRI. We will then test whether the performance of the mp-MRI can be improved by the addition of an advanced diffusion-weighted MRI technique, which uses a biophysical model to characterise tissue microstructure called VERDICT; Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours. INNOVATE is a prospective single centre cohort study in 365 patients. mp-MRI will act as the reference standard for the biomarker panel. A clinical outcome based reference standard based on biopsy, mp-MRI and follow-up will be used for VERDICT MRI.
  
  
  
  We expect the combined effect of biomarkers and VERDICT MRI will improve care by better detecting aggressive prostate cancer early and make mp-MRI before biopsy economically viable for universal NHS adoption.
  
  
  
  INNOVATE is registered on ClinicalTrials.gov, with reference NCT02689271 .
authors: UCL Centre for Medical Imaging, 5th floor, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK. edward.johnston@uclh.nhs.uk.
authors: Edward
authors: 0000-0002-8504-2968
authors: E
authors: Johnston
authors: Research Department for Tissue & Energy, Division of Surgery & Interventional Science, Wing 2.4 Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Addenbrookes Hospital, Level 4, Pathology Block, Hills Road, Cambridge, CB20QQ, UK.
authors: Hayley
authors: H
authors: Pye
authors: Department of Computer Science, UCL, Gower Street, London, WC1E 6BT, UK.
authors: Elisenda
authors: E
authors: Bonet-Carne
authors: Department of Computer Science, UCL, Gower Street, London, WC1E 6BT, UK.
authors: Eleftheria
authors: E
authors: Panagiotaki
authors: Department of Research Pathology, UCL Cancer Institute, Rockefeller Building, 21 University Street, London, WC1E 6JJ, UK.
authors: Dominic
authors: D
authors: Patel
authors: Molecular Oncology group, UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK.
authors: Myria
authors: M
authors: Galazi
authors: Research Department for Tissue & Energy, Division of Surgery & Interventional Science, Wing 2.4 Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Addenbrookes Hospital, Level 4, Pathology Block, Hills Road, Cambridge, CB20QQ, UK.
authors: Susan
authors: S
authors: Heavey
authors: Research Department for Tissue & Energy, Division of Surgery & Interventional Science, Wing 2.4 Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Addenbrookes Hospital, Level 4, Pathology Block, Hills Road, Cambridge, CB20QQ, UK.
authors: Lina
authors: L
authors: Carmona
authors: Department of Research Pathology, UCL Cancer Institute, Rockefeller Building, 21 University Street, London, WC1E 6JJ, UK.
authors: Alexander
authors: A
authors: Freeman
authors: Department of Research Pathology, UCL Cancer Institute, Rockefeller Building, 21 University Street, London, WC1E 6JJ, UK.
authors: Giorgia
authors: G
authors: Trevisan
authors: UCL Centre for Medical Imaging, 5th floor, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK.
authors: Clare
authors: C
authors: Allen
authors: UCL Centre for Medical Imaging, 5th floor, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK.
authors: Alexander
authors: A
authors: Kirkham
authors: Research Department for Tissue & Energy, Division of Surgery & Interventional Science, Wing 2.4 Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Addenbrookes Hospital, Level 4, Pathology Block, Hills Road, Cambridge, CB20QQ, UK.
authors: Keith
authors: K
authors: Burling
authors: UCL Centre for Medical Imaging, 5th floor, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK.
authors: Nicola
authors: N
authors: Stevens
authors: Department of Computer Science, UCL, Gower Street, London, WC1E 6BT, UK.
authors: David
authors: D
authors: Hawkes
authors: Division of Surgery, 4th floor, 21 University Street, London, WC1E, UK.
authors: Mark
authors: M
authors: Emberton
authors: Division of Surgery, 4th floor, 21 University Street, London, WC1E, UK.
authors: Caroline
authors: C
authors: Moore
authors: Division of Surgery, 4th floor, 21 University Street, London, WC1E, UK.
authors: Hashim U
authors: HU
authors: Ahmed
authors: UCL Centre for Medical Imaging, 5th floor, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK.
authors: David
authors: D
authors: Atkinson
authors: Department of Research Pathology, UCL Cancer Institute, Rockefeller Building, 21 University Street, London, WC1E 6JJ, UK.
authors: Manuel
authors: M
authors: Rodriguez-Justo
authors: Molecular Oncology group, UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK.
authors: Tony
authors: T
authors: Ng
authors: Department of Computer Science, UCL, Gower Street, London, WC1E 6BT, UK.
authors: Daniel
authors: D
authors: Alexander
authors: Research Department for Tissue & Energy, Division of Surgery & Interventional Science, Wing 2.4 Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Addenbrookes Hospital, Level 4, Pathology Block, Hills Road, Cambridge, CB20QQ, UK.
authors: Hayley
authors: H
authors: Whitaker
authors: UCL Centre for Medical Imaging, 5th floor, Wolfson House, 4 Stephenson Way, London, NW1 2HE, UK.
authors: Shonit
authors: S
authors: Punwani
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor; D001706:Biopsy; D000066491:Clinical Decision-Making; D002985:Clinical Protocols; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000652:urine*; D012107:Research Design; D057188:Workflow
chemical_list: D014408:Biomarkers, Tumor