Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.

To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.

Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.

Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.

A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.

The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.

The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.

European urology. 2017 Apr 10 [Epub ahead of print]

Steven M Walker, Laura A Knight, Andrena M McCavigan, Gemma E Logan, Viktor Berge, Amir Sherif, Hardev Pandha, Anne Y Warren, Catherine Davidson, Adam Uprichard, Jaine K Blayney, Bethanie Price, Gera L Jellema, Christopher J Steele, Aud Svindland, Simon S McDade, Christopher G Eden, Chris Foster, Ian G Mills, David E Neal, Malcolm D Mason, Elaine W Kay, David J Waugh, D Paul Harkin, R William Watson, Noel W Clarke, Richard D Kennedy

Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK; Almac Diagnostics, Craigavon, UK., Almac Diagnostics, Craigavon, UK., Department of Urology, Oslo University Hospital, Oslo, Norway., Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea University, Umea, Sweden., Department of Microbial Sciences, University of Surrey, Guildford, UK., Department of Pathology, Addenbrooke's Hospital, Cambridge, UK., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK., Department of Pathology, Oslo University Hospital, Oslo, Norway., Department of Urology, Royal Surrey County Hospital, Guildford, UK., Institute of Translational Medicine, University of Liverpool, Merseyside, UK., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK; Department of Urology, Oslo University Hospital, Oslo, Norway; Department of Molecular Oncology, Oslo University Hospital/Institute for Cancer Research, Oslo, Norway; Prostate Cancer Research Group, Centre for Molecular Medicine Norway (NCMM), University of Oslo and Oslo University Hospitals, Forskningsparken, Oslo, Norway., Uro-oncology Research Group, Cambridge Research Institute, Cambridge, UK., Wales Cancer Bank, Cardiff University, School of Medicine, Health Park, Cardiff, UK., Department of Pathology, RCSI, Beaumont Hospital, Dublin, Ireland., UCD School of Medicine, Conway Institute, University College Dublin, Belfield, Dublin, Ireland., Christie NHS Foundation Trust, Manchester, UK., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK; Almac Diagnostics, Craigavon, UK. Electronic address: .

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