The ReIMAGINE prostate cancer risk study protocol: A prospective cohort study in men with a suspicion of prostate cancer who are referred onto an MRI-based diagnostic pathway with donation of tissue, blood and urine for biomarker analyses.

Introduction The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic). Methods ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes. Results Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers. Conclusion The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy.

[1]  M. Cooperberg,et al.  Routine Use of Magnetic Resonance Imaging for Early Detection of Prostate Cancer Is Not Justified by the Clinical Trial Evidence. , 2020, European urology.

[2]  H. Ahmed,et al.  All change in the prostate cancer diagnostic pathway , 2020, Nature Reviews Clinical Oncology.

[3]  D. Margolis,et al.  MRI‐Targeted or Standard Biopsy for Prostate‐Cancer Diagnosis , 2018, The New England journal of medicine.

[4]  A. Atala.  Re: Genomic Hallmarks of Localized, Non-Indolent Prostate Cancer. , 2017, The Journal of urology.

[5]  P. Jänne,et al.  Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer , 2017, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[6]  Nicolai J. Birkbak,et al.  Tracking the Evolution of Non‐Small‐Cell Lung Cancer , 2017, The New England journal of medicine.

[7]  David J. Hawkes,et al.  Development and Phantom Validation of a 3-D-Ultrasound-Guided System for Targeting MRI-Visible Lesions During Transrectal Prostate Biopsy , 2017, IEEE Transactions on Biomedical Engineering.

[8]  J. Oxley,et al.  Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial , 2017, European urology.

[9]  A. D'Amico.  Active Surveillance Versus Treatment of Prostate Cancer: Should Metastasis Be the Primary End Point? , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. Parmar,et al.  Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study , 2017, The Lancet.

[11]  R. Laing,et al.  Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial , 2016, The Lancet.

[12]  S. Bentink,et al.  A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result , 2015, Prostate Cancer and Prostatic Disease.

[13]  T. D. de Reijke,et al.  Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer , 2015, Clinical Cancer Research.

[14]  Andre Marziali,et al.  Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform , 2014, Oncotarget.

[15]  Yipeng Hu,et al.  Image-directed, tissue-preserving focal therapy of prostate cancer: a feasibility study of a novel deformable magnetic resonance-ultrasound (MR-US) registration system , 2013, BJU international.

[16]  B. Carey,et al.  Magnetic resonance imaging for the detection, localisation, and characterisation of prostate cancer: recommendations from a European consensus meeting. , 2011, European urology.

[17]  M. Nykter,et al.  Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer. , 2018, Cancer discovery.