Medical Oncology Epithelial Cell Adhesion Molecule-positive Circulating Tumor Cells as Predictive Biomarker in Patients With Prostate Cancer Robert J. Amato, Vladislava Melnikova, Yujian Zhang, Wen Liu, Somyata Saxena, Parth K. Shah, Brett T. Jensen, Karen E. Torres, and Darren W. Davis OBJECTIVE To assess the use of circulating tumor cells (CTCs) as a longitudinal endpoint factor for clinical monitoring of patients with prostate cancer and to evaluate the association among the baseline CTC number, various clinical characteristics, and survival. MATERIALS AND METHODS The CTCs were enumerated using the CellSearch Food and Drug Administrationecleared CTC kit in 202 patients with prostate cancer. Variables, including metastatic site, prostate-specific antigen level, Gleason score, testosterone level, and use of androgen treatment, were tested for association with the CTC number. The probability of patient survival over time was estimated using the Kaplan-Meier method. RESULTS The baseline CTC numbers were strongly associated with survival (P <.0001), with overall survival significantly poorer in patients with 5 CTCs. Significantly greater CTC numbers were observed in patients with bone metastasis (mean 41.12 CTCs) than in those with lymph node metastasis (mean 2.53 CTC, P ¼ .026). Analysis of the association between the CTC count and prostate-specific antigen level revealed a weak positive correlation (correlation coefficient r ¼ 0.2695, P ¼ .0007). The CTC number also correlated with the Gleason score (P ¼ .0138) and lower testosterone level (P <.0001). Patients without androgen depletion had significantly lower CTC numbers (mean 2.70) than those with androgen depletion (mean 26.39, P <.0001). CONCLUSION The baseline CTC counts were predictive of patient survival and correlated significantly with the clinical characteristics of patients with prostate cancer. Our study results have confirmed previous findings that support the use of CTC enumeration as a prognostic biomarker for patients with prostate cancer. UROLOGY 81: 1303e1307, 2013. Ó 2013 Elsevier Inc. P rostate cancer is the most common non- dermatologic malignancy in men and the second leading cause of male cancer-related deaths in the United States. 1,2 The prostate-specific antigen (PSA) blood level is widely used as a diagnostic, predictive, and prognostic marker of prostate cancer. 3,4 The PSA level, however, might not accurately reflect the disease status, 5 because increases in the PSA level are only slightly associated with survival. Hence, more reliable indicators of prostate cancer disease status are needed. The shedding of tumor cells into the circulation results in metastatic cancer spread. 6,7 The presence of circulating tumor cells (CTCs) in the peripheral circulation during the early stages of cancer development has increasingly been considered a hallmark of cancer progression. The CTC level has been correlated with the prognosis in patients with prostate cancer. 8-10 In addition to providing prog- nostic information for prostate cancer, molecular analysis of CTCs has the potential to predict the sensitivity, or resistance, to drug treatment. 11-14 In recent years, several CTC isolation techniques have been reported, but only one method, CellSearch (Veridex, Raritan, NJ), is analytically valid and has been cleared by the Food and Drug Administration. 15 Most CTC detection methods such as MACs, CellSearch (Veridex), and the CTC-chip depend on immuno- magnetic separation, in which positive selection of epithelial cell adhesion molecule-expressing CTCs allows them to be distinguished from normal blood cells. 16-19 The enriched cells are further classified as CTCs on the basis of morphologic limits and criteria for cytokeratin staining, nucleus displaying, and exclusion of white blood cells (CD45 staining). Studies of patients with progressive metastatic breast, colorectal, or prostate cancer have shown that CTCs are indicators of prognosis before and after therapy using discrete disease cutoff points Financial Disclosure: The authors declare that they have no relevant financial interests. From the Division of Oncology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX; the UT Memorial Hermann Cancer Center, Houston, TX; and ApoCell, Incorporated, Houston, TX Reprint requests: Robert J. Amato, D.O., University of Texas Memorial Hermann Cancer Center, 6410 Fannin Street, Suite 830, Houston, TX 77030. E-mail: robert. amato@uth.tmc.edu Submitted: March 12, 2012, accepted (with revisions): October 24, 2012 ª 2013 Elsevier Inc. 0090-4295/12/$36.00 1303 All Rights Reserved http://dx.doi.org/10.1016/j.urology.2012.10.041