Prognostic Role and HER2 Expression of Circulating Tumor Cells in Peripheral Blood of Patients Prior to Radical Cystectomy: A Prospective Study
Menée sur 100 patients atteints d'un carcinome urothélial de la vessie de stade avancé, non métastatique et traité par cystectomie radicale, cette étude prospective évalue l'association entre le niveau sanguin préopératoire des cellules tumorales circulantes, le niveau d'expression du récepteur HER2 de ces cellules et les caractéristiques clinico-pathologiques de la maladie
Background : Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTCs) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB).
Objective : Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTCs in patients with clinically nonmetastatic UCB.
Design, setting, and participants : Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTCs and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization.
Intervention : Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy.
Measurements : Outcomes were assessed according to CTC status. HER2 expression of CTCs was compared with that of the corresponding primary tumor and lymph node metastasis.
Results and limitations : CTCs were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1–100). Presence, number, and HER2 status of CTCs were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality (p values: ≤0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤0.003). HER2 was strongly positive in CTCs from 3 of 22 patients (14%). There was discordance between HER2 expression on CTCs and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size.
Conclusions : Preoperative CTCs are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTCs may serve as an indication for multimodal therapy. Molecular characterization of CTCs may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials.
European urology , résumé, 2011