TMPRSS2-ERG status and biochemical recurrence following radiotherapy for intermediate-risk prostate cancer

Alan Dal Pra; Fiona Warde; Adrian Shea Ishkanian; Alice Meng; Chad Malloff; Wan Lam; Jenna Sykes; Melania Pintile; Jeremy Squire; Theo van der Kwast; Andrew Evans; Michael Milosevic; Robert Glen Bristow

doi:10.1200/jco.2012.30.5_suppl.11

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TMPRSS2-ERG status and biochemical recurrence following radiotherapy for intermediate-risk prostate cancer

Journal article

Peer reviewed

TMPRSS2-ERG status and biochemical recurrence following radiotherapy for intermediate-risk prostate cancer

Alan Dal Pra, Fiona Warde, Adrian Shea Ishkanian, Alice Meng, Chad Malloff, Wan Lam, Jenna Sykes, Melania Pintile, Jeremy Squire, Theo van der Kwast, …

Journal of clinical oncology, Vol.30(5_suppl), pp.11-11

2012-02-10

DOI: https://doi.org/10.1200/jco.2012.30.5_suppl.11

Abstract

11 Background: Approximately 50% of prostate cancers (PC) contain TMPRSS2-ERG gene fusions leading to ERG overexpression. Pre-clinical data suggest that these fusions are due to altered DNA double-strand break repair status which could have therapeutic ramification for the use of radiotherapy (RT) and PARP inhibitors. The aim of this study was to correlate TMPRSS2-ERG status to biochemical failure following clinical induction of DNA breaks in the form of image-guided radiotherapy (IGRT) in intermediate-risk PC. Methods: Pre-treatment biopsies from two separate cohorts of intermediate-risk PC patients (T1/T2, GS < 8, PSA < 20ng/ml) were analyzed: 1) 126 patients assessed by array Comparative Genomic Hybridization (aCGH) for TMPRSS2:ERG fusion; and 2) 121 patients assessed by tissue microarray (TMA) for ERG expression by immunohistochemistry (IHC). All patients received IGRT with a median dose of 79.8 Gy (60-79.8 Gy). TMPRSS2:ERG status was correlated to Gleason score, T stage, initial PSA and biochemical-free relapse rate (bFRR; Phoenix definition: nadir + 2ng/ml). Results: At a median follow-up time of 6.36 years, the biochemical relapse event rate was 37% and 18% in the aCGH and IHC cohorts, respectively. ERG expression by IHC was found in 49.6% of the 121 PC. TMPRSS2-ERG status was not correlated to increased Gleason score, pre-treatment PSA or T stage. On multivariate analyses in models containing clinical factors, TMPRSS2:ERG status (either using aCGH or IHC) was not prognostic for biochemical outcome (ERG expression: HR=0.78, 95% CI: 0.33-1.85; p= 0.568; TMPRSS2-ERG fusion: HR=0.71, 95% CI: 0.35-1.41; p=0.326). Conclusions: In two separate cohorts, TMPRSS2-ERG status was not prognostic for bRFR after IGRT. Although a trend was observed, these clinical data do not support the hypothesis that these cancers have DNA repair defects that render them significantly more radiosensitive when compared to other PC. Further clinical trials are required to understand the utility of TMPRSS2:ERG status and response to DNA damaging agents, including that of PARP inhibitors. The trans-Canadian PROFIT trial is completing accrual of close to 1200 patients allowing for TMPRSS2:ERG studies in a larger RT cohort.

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Title: TMPRSS2-ERG status and biochemical recurrence following radiotherapy for intermediate-risk prostate cancer
Creators: Alan Dal Pra - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Fiona Warde - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Adrian Shea Ishkanian - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Alice Meng - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Chad Malloff - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Wan Lam - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Jenna Sykes - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Melania Pintile - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Jeremy Squire - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Theo van der Kwast - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Andrew Evans - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Michael Milosevic - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Robert Glen Bristow - Department of Radiation Oncology, Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; British Columbia Cancer Research Centre and University of British Columbia, Vancouver, BC, Canada; Department of Biostatistics, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, University Health Network, Toronto, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
Publication Details: Journal of clinical oncology, Vol.30(5_suppl), pp.11-11
Academic Unit: Miller School of Medicine; UMMG Dept of Radiation Oncology
Language: English
Resource Type: Journal article
Record Identifier: 991031598148802976