Originally published as JCO Early Release 10.1200/JCO.2007.15.0441 on September 15 2008

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Prognostic Significance of Disseminated Tumor Cells in the Bone Marrow of Prostate Cancer Patients Treated With Neoadjuvant Hormone Treatment

Jens Köllermann, Steffen Weikert, Martin Schostak, Carsten Kempkensteffen, Klaus Kleinschmidt, Thomas Rau, Klaus Pantel

From the Institutes of Pathology, Tumor Biology, and Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf; Department of Urology, Campus Benjamin Franklin, Charite' Universitätsmedizin Berlin; and the Department of Urology, Dr Horst-Schmidt-Kliniken, Wiesbaden, Germany

Corresponding author: Klaus Pantel, MD, PhD, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr 52, D-20246 Hamburg, Germany; e-mail: pantel{at}uke.uni-hamburg.de

Purpose To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy.

Patients and Methods Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients’ outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months.

Results DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014).

Conclusion The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.

published online ahead of print at www.jco.org on September 15, 2008.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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