Detection of Circulating Tumor Cells in Metastatic and Clinically Localized Urothelial Carcinoma

OBJECTIVE To examine the incidence and prognostic value of circulating tumor cells (CTCs) in urothelial cancer (UC). The detection of CTCs is prognostic in several cancer types. METHODS A total of 44 subjects with UC were assessed for CTCs using CellSearch Technology and 7.5 mL of peripheral blood, sorted by magnetic separation (epithelial cell adhesion molecule positive) and immunofluorescent staining (positive for cytokeratin 8, 18, or 19, negative for CD45, positive for 4',6-diamidino-2-phenylindole) to identify the CTCs. RESULTS Five (17%) of 30 subjects with clinically localized and 7 (50%) of 14 subjects with metastatic UC had >= 1 detectable CTC (range 1-177). Six subjects had >= 5 CTCs. Fluorescence in situ hybridization analysis was performed in 20 samples from 18 unique subjects using the UroVysion probe set. Copy number gains consistent with neoplasm were observed in those with measurable CTCs but not in any of the CTC-negative samples tested. With a median follow-up of 337 days, all 7 patients with metastasis and detectable CTCs had died compared with 3 (43%) of the 7 with metastasis but without detectable CTCs. CONCLUSION CTCs are commonly observed in metastatic UC. CTCs were observed in 50% of the patients with metastatic UC tested. Fluorescence in situ hybridization analysis confirmed the aneusomic chromosomal content in the CTCs. These findings suggest that measurable CTCs might be prognostic for shortened survival in patients with metastatic UC, although the optimal threshold for a positive finding is unknown. CTCs were also detected in a subset of patients with clinically localized disease, identifying a potential high-risk, preoperative group for future study. UROLOGY 78: 863-867, 2011. (C) 2011 Elsevier Inc.