Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel

Michiel Strijbos, Jan willem Gratama, Paul Schmitz, C Rao, Wendy Onstenk, GV Doyle, MC Miller, Ronald de Wit, LWMM Terstappen, Stefan Sleijfer

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Purpose: We investigated whether serum markers of angiogenesis endothelin-1 (ET-1) and tissue factor (TF), and/or markers of vascular damage such as circulating endothelial cells (CECs), or their relative changes during treatment, were prognostic for overall survival (OS) in castration resistant prostate cancer (CRPC) patients. Additionally, we combined these markers with circulating tumour cells (CTCs) to construct a predictive nomogram for treatment outcome. Patients and methods: One hundred and sixty two CRPC patients treated with a docetaxel containing regimen had blood drawn before and at 2-5 weeks and 6-8 weeks after treatment start. Prospectively determined CTC and CEC levels, and retrospectively measured serum concentrations of ET-1 (pg/mL) and TF (pg/mL) were evaluated to determine their prognostic value for OS. Results: Baseline CEC, TF and ET-1 were not prognostic for OS. A >= 3.8-fold increase in CEC 2-5 weeks after treatment initiation was associated with decreased OS (median 10.9 versus 16.8 months; P = 0.015), as was any decrease in IF levels compared to baseline levels (median 11.9 versus 21.5 months; P = 0.0005). As previously published, baseline and CTC counts >= 5 at 2-5 weeks were also predictive of decreased OS. Combining CTC with changes in TF and CEC 2-5 weeks after treatment initiation yielded four groups differing in OS (median OS 24.2 versus 16.0 versus 11.4 versus 6.1 months; P < 0.0001). Conclusion: CEC, CTC and IF levels alone and combined can predict early on OS in CRPC patients treated with docetaxel-based therapy. A prospective study to confirm the use of these markers for patient management is needed. (C) 2010 Elsevier Ltd. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)2027-2035
Number of pages9
JournalEuropean Journal of Cancer
Issue number11
Publication statusPublished - 2010

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