Watchful waiting for localized prostate cancer in the PSA era: what have been the triggers for intervention?

Circulating tumour cells (CTC) have prognostic relevance for patients with different metastatic carcinomas. Detection of CTC using the CellSearch system has also been reported in bladder cancer, but mainly in patients with metastatic disease. This is the largest report demonstrating that detection of CTC in non-metastatic bladder cancer patients is feasible using the CellSearch system. Presence of CTC may be predictive for early systemic disease. OBJECTIVE To prospectively detect and evaluate the biological significance of circulating tumour cells (CTC) in patients with bladder cancer, especially in those patients with non-metastatic, advanced bladder cancer (NMABC). PATIENTS AND METHODS Between July 2007 and January 2009, blood samples of 50 consecutive patients with localized bladder cancer and five patients with metastatic disease scheduled for cystectomy were prospectively investigated for CTC. Peripheral blood (7.5 ml) was drawn before cystectomy. Detection of CTC was performed using the USA Food and Drug Administration-approved CellSearchTM system. Data were compared with the clinical and histopathological findings. RESULTS CTC were detected in 15 of 50 patients (30%) with non-metastatic disease and five of five patients with metastatic disease. The overall mean number of CTC was 33.7 (range: 1-372; median: 2). In non-metastatic patients, the mean number of CTC was 3.1 (range: 1-11; median: 1). Except for a univariate association between CTC with vessel infiltration (P = 0.047), all other common clinical and histopathological parameters did not reveal a significant correlation with CTC detection. A median 1-year follow up was available for 53 patients (96.4%). Ten out of 19 preoperatively CTC-positive patients died as a result of cancer progression. CTC-positive patients showed significantly worse overall (P = 0.001), progression-free (P < 0.001) and cancer specific survival (P < 0.001) compared to preoperatively CTC-negative patients. CONCLUSION This is the largest study demonstrating that detection of CTC in NMABC patients is feasible using the CellSearchTM system. Our findings suggest that the presence of CTC may be predictive for early systemic disease.