Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology
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Walker, SM, Knight, LA, McCavigan, AM, Logan, GE, Berge, V, Sherif, A, Pandha, Hardev, Warren, AY, Davidson, C, Uprichard, A , Blayney, JK, Price, B, Jellema, GL, Svindland, A, McDade, SS, Eden, CG, Foster, C, Mills, IG, Neal, DE, Mason, MD, Kay, EW, Waugh, DJ, Harkin, DP, Watson, RW, Clarke, NW and Kennedy, RD (2017) Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology European Urology, 72 (4). pp. 509-518.
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Abstract
BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. DESIGN, SETTING & PARTICIPANTS: 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. OUTCOME MEASURES & STATISTICAL ANALYSIS: 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 analyzed using multivariable Cox regression and log-rank analysis. RESULTS & LIMITATIONS: 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 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 CAPRA-S identified patients at 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. CONCLUSIONS: The Metastatic Assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. PATIENT SUMMARY: 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.
| Item Type: | Article | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Subjects : | Biosciences and Medicine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions : | Faculty of Health and Medical Sciences > School of Biosciences and Medicine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Date : | 10 April 2017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identification Number : | 10.1016/j.eururo.2017.03.027 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright Disclaimer : | Copyright 2017 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uncontrolled Keywords : | prostate cancer, prognostic, recurrence, progression, Metastatic Assay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Depositing User : | Symplectic Elements | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date Deposited : | 02 May 2017 17:54 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Last Modified : | 13 Sep 2017 13:13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| URI: | http://epubs.surrey.ac.uk/id/eprint/814092 |
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