Detection and Clinical Significance of Circulating Tumor Cells in Patients Undergoing Radical Cystectomy for Urothelial Bladder Cancer.

INTRODUCTION: Estimation of prognosis is patients undergoing radical cystectomy is often unreliable, as occult disease remains undetected by conventional diagnostic tools. The purpose of this study was to evaluate the feasibility and the clinical significance of a polymerase chain reaction assay to detect cytokeratin 7 (CK7) mRNA expression in peripheral blood cells of patients undergoing radical cystectomy for clinically nonmetastatic bladder cancer. PATIENTS AND METHODS: From 2005 to 2009, 59 patients undergoing radical cystectomy and pelvic lymph node dissection were prospectively investigated. Peripheral blood was collected prior to surgery, and a nested polymerase chain reaction assay was developed to identify patients with circulating cells expressing CK7 mRNA. Preoperative, histopathologic data and clinical outcome were compared with CK7 findings. RESULTS: CK7 expression was detected in 23 (38.9%) of 59 patients and correlated to T stage and lymph node status. After a median follow-up of 42 months, 29 patients experienced a recurrence, whereas 36 died. The presence of CK7-positive cells was significantly associated with an increased risk for recurrence and decreased survival as compared with patients who were CK7-negative (P < .001 and P < .001, respectively; hazard ratios of 8.77 and 5.2 for recurrence and overall death, respectively). The detection of CK7-positive cells was an independent predictor of recurrence and death in a multivariable analysis. CONCLUSION: The detection of CK7 mRNA in the circulating cells of patients undergoing radical cystectomy for urothelial cancer identifies those with significantly increased risk of cancer recurrence and death.

Celecoxib for the prevention of nonmuscle invasive bladder cancer: results from a matched control study.

OBJECTIVES: New targets and approaches are under investigation for the treatment of nonmuscle invasive bladder cancer (NMIBC). Preclinical data suggest cyclooxygenase-2 (COX-2) as a promising target. Celecoxib, a COX-2 selective inhibitor, inhibits tumor development and enhances survival, both in vitro and in vivo models of bladder cancer. Therefore, we conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC. METHODS: Treatment with celecoxib was administered orally for 12 months and compared with a contemporary series of patients treated with intravesical mitomycin C (MMC), given weekly for 4 weeks and then monthly for 11 months. Primary endpoints were time to first recurrence and adverse events. RESULTS: From 2003 through 2006, 58 patients were treated with celecoxib and compared with 66 patients receiving MMC. After a median follow up of 75 months, 49 patients were disease free, including 23 (34.85%) in the MMC group and 26 (44.8%) in the celecoxib group. Median disease-free interval was 67 months [95% confidence interval (CI) 35.8 to NA] versus 41 months (95% CI 27.1-67.1; log-rank p = 0.25) for patients treated with MMC and celecoxib, respectively. In the multivariate analysis, treatment was not found to be an independent predictor for recurrence [hazard ratio (HR) 0.76, 95% CI 0.47-1.22, p = 0.25). Overall, 45 AEs were recorded in 35/124 patients. There were no differences between the two groups. CONCLUSIONS: Our data support a clinical benefit of celecoxib and encourage future trials in which COX-2 inhibitors may be tested in selected patients with NMIBC.