Circulating Tumor Cells in Patients with Castration-Resistant Prostate Cancer Baseline Values and Correlation with Prognostic Factors

Abstract

Purpose: Circulating tumor cells (CTC) have been recently accepted by the Food and Drug Administration of the United States as a prognostic tool in advanced prostate cancer. However, a number of questions remain about the use of the test. The optimal clinical cut-off has never been determined. Also, the predictive value of CTCs in the setting of low-burden advanced prostate cancer has not been evaluated. Herein we describe our experience with the CellSearch method of CTC enumeration. Experimental Design: CTCs enumerated from 100 patients with castration-resistant prostate cancer were correlated with clinicopathologic characteristics and conventional biomarkers, such as prostatespecific antigen and lactate dehydrogenase. Patients received ongoing medical oncologic follow-up for up to 26 months, and overall survival status was documented.Results: Forty-nine of the patients (49%) were alive at the end of the study. CTC counts correlate well with overall survival (P < 0.001) but are also tightly interrelated to other biomarkers. Threshold analysis identified 4 CTC/7.5 cc (compared with the approved value of 5) as an optimal cut-off value with respect to correlation with survival outcomes as well as predictive of metastatic disease. Univariate analysis confirmed a tight interrelationship between cut-off CTC values and biomarkers. Multivariate analysis with bootstrap sampling validation identified lactate dehydrogenase (P = 0.002) and CTCs (P = 0.001) as independently prognostically significant. Conclusions: Baseline CTC values provide important prognostic information and specific prediction of metastatic disease. Their presence correlates with classic biomarkers. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1904 -13)

The Cohesive Metastasis Phenotype in Human Prostate Cancer

“…New technological advances permit the retrieval of CTCs and CTC-clusters in patients with metastatic castration-resistant prostate cancer (mCRPC) [3,6] and characterizing the molecular determinants may offer new strategies to prevent metastasis with early intervention. Others suggest that CTCs can be sampled to determine some aspects of the tumor biology, for example, AR expression and epidermal growth factor receptor (EGFR/Her1) overexpression [34], which makes the ability to analyze CTC-clusters potentially a powerful tool.…”

Epithelial-Mesenchymal Transition: A Hallmark in Metastasis Formation Linking Circulating Tumor Cells and Cancer Stem Cells

“…Therefore, CTCs enable tracking of one of the first steps in a metastatic cascade and provide great potential for prognosis and monitoring of treatment response in many cancers. The presensce of CTCs was demonstrated to be an independent adverse prognostic factor in metastatic [126,127,128] and early breast cancer [129], metastatic colorectal cancer [130], castration-resistant prostate cancer [131,132] or resectable non-small cell lung cancer [133,134]. …”

Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

“…However, current serum marker or high-resolution imaging technologies are unable to identify micrometastasis during the course of cancer progression and give the accurate information regarding the treatment response. As an important intermediate event in metastasis, the hypothesis was made that CTC count could reflect the ongoing metastasis (Goodman et al 2009). Accumulating observations correlated CTCs with clinical outcome parameters such as progression-free survival (PFS) and overall survival (OS).…”