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Circulating Tumor Cell Number and Prognosis in Progressive Castration-Resistant Prostate Cancer

Authors' Affiliations: ¹ Genitourinary Oncology Service, Department of Medicine, ² Department of Epidemiology and Biostatistics, ³ Clinical Laboratories, ⁴ Urology Service, Department of Surgery, and ⁵ Department of Radiology, Memorial Sloan-Kettering Cancer Center; and ⁶ Department of Medicine, Joan and Sanford E. Weill College of Medicine of Cornell University, New York, New York

Requests for reprints: Howard I. Scher, Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 646-422-4323; Fax: 212-988-0851; E-mail: Scherh{at}mskcc.org, or Martin Fleisher, Chairman, Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. E-mail: Fleishem{at}mskcc.org.

Purpose: The development of tumor-specific markers to select targeted therapies and to assess clinical outcome remains a significant area of unmet need. We evaluated the association of baseline circulating tumor cell (CTC) number with clinical characteristics and survival in patients with castrate metastatic disease considered for different hormonal and cytotoxic therapies.

Experimental Design: CTC were isolated by immunomagnetic capture from 7.5-mL samples of blood from 120 patients with progressive clinical castrate metastatic disease. We estimated the probability of survival over time by the Kaplan-Meier method. The concordance probability estimate was used to gauge the discriminatory strength of the informative prognostic factors.

Results: Sixty-nine (57%) patients had five or more CTC whereas 30 (25%) had two cells or less. Higher CTC numbers were observed in patients with bone metastases relative to those with soft tissue disease and in patients who had received prior cytotoxic chemotherapy relative to those who had not. CTC counts were modestly correlated to measurements of tumor burden such as prostate-specific antigen and bone scan index, reflecting the percentage of boney skeleton involved with tumor. Baseline CTC number was strongly associated with survival, without a threshold effect, which increased further when baseline prostate-specific antigen and albumin were included.

Conclusions: Baseline CTC was predictive of survival, with no threshold effect. The shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease, and provides unique information relative to prognosis.

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