Genomic Evaluation of Multiparametric Magnetic Resonance Imaging-visible and -nonvisible Lesions in Clinically Localised Prostate Cancer.

The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification.

To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease.

Multicore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa.

Low-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients.

Correlations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication.

A total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up.

Our study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied.

Our study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed.

European urology oncology. 2018 Sep 05 [Epub]

Marina A Parry, Shambhavi Srivastava, Adnan Ali, Alessio Cannistraci, Jenny Antonello, João Diogo Barros-Silva, Valentina Ubertini, Vijay Ramani, Maurice Lau, Jonathan Shanks, Daisuke Nonaka, Pedro Oliveira, Thomas Hambrock, Hui Sun Leong, Nathalie Dhomen, Crispin Miller, Ged Brady, Caroline Dive, Noel W Clarke, Richard Marais, Esther Baena

Molecular Oncology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Molecular Oncology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Computational Biology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Genitourinary Cancer Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester Cancer Research Centre, Manchester, UK; Prostate Oncobiology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Clinical and Experimental Pharmacology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Prostate Oncobiology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Department of Surgery, The Christie NHS Foundation Trust, Manchester, UK., Department of Pathology, The Christie NHS Foundation Trust, Manchester, UK., Department of Radiology, The Christie NHS Foundation Trust, Manchester, UK., Computational Biology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Molecular Oncology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Computational Biology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; RNA Biology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK., Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Genitourinary Cancer Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester Cancer Research Centre, Manchester, UK; Department of Surgery, The Christie NHS Foundation Trust, Manchester, UK; Department of Urology, Salford NHS Foundation Trust, Salford, UK. Electronic address: ., Molecular Oncology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK. Electronic address: ., Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK; Prostate Oncobiology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK. Electronic address: .

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