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Annals of Oncology Advance Access originally published online on August 11, 2008
Annals of Oncology 2009 20(1):27-33; doi:10.1093/annonc/mdn544
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

urogenital tumours

Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience

D. Olmos1,2, H.-T. Arkenau1, J. E. Ang1, I. Ledaki2, G. Attard1,2, C. P. Carden1, A. H. M. Reid1,2, R. A'Hern3, P. C. Fong1,2, N. B. Oomen1, R. Molife1, D. Dearnaley4, C. Parker4, L. W. M. M. Terstappen5 and J. S. de Bono1,2,*

1 Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton
2 Section of Medicine, The Institute of Cancer Research, Sutton
3 ICR Clinical Trials and Statistical Unit, Section of Clinical Trials, The Institute of Cancer Research, Sutton
4 Academic Urology Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK
5 Immunicon Corporation, Huntington Valley, PA, USA

* Correspondence to: Dr Johann de Bono, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5P2, UK. Tel: +44-208-6426011; Fax: +44-208-6427979; E-mail: johann.de-bono{at}icr.ac.uk

Background: The purpose of this study was to evaluate the association of circulating tumour cell (CTC) counts, before and after commencing treatment, with overall survival (OS) in patients with castration-resistant prostate cancer (CRPC).

Experimental design: A 7.5 ml of blood was collected before and after treatment in 119 patients with CRPC. CTCs were enumerated using the CellSearch®System.

Results: Higher CTC counts associated with baseline characteristics portending aggressive disease. Multivariate analyses indicated that a CTC ≥5 was an independent prognostic factor at all time points evaluated. Patients with baseline CTC ≥5 had shorter OS than those with <5 [median OS 19.5 versus >30 months, hazard ratio (HR) 3.25, P = 0.012]; patients with CTC >50 had a poorer OS than those with CTCs 5–50 (median OS 6.3 versus 21.1 months, HR 4.1, P < 0.001). Patients whose CTC counts reduced from ≥5 at baseline to <5 following treatment had a better OS compared with those who did not. CTC counts showed a similar, but earlier and independent, ability to time to disease progression to predict OS.

Conclusion: CTC counts predict OS and provide independent prognostic information to time to disease progression; CTC dynamics following therapy need to be evaluated as an intermediate end point of outcome in randomised phase III trials.

Key words: biomarkers, castration-resistant prostate cancer, circulating tumour cell

Received for publication April 4, 2008. Revision received June 18, 2008. Revision received June 26, 2008. Accepted for publication July 4, 2008.


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