Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Eur Urol. 2012 Apr;61(4):810-7. doi: 10.1016/j.eururo.2012.01.017. Epub 2012 Jan 20.
Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB).
Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC 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 CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization.
Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy.
Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis.
CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1-100). Presence, number, and HER2 status of CTC 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 CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC 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.
Preoperative CTC 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 CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials.
初步研究表明，循环肿瘤细胞（CTC）在晚期非转移性膀胱癌（UCB）患者中的预后价值。
前瞻性分析临床非转移性 UCB 患者 CTC 的临床相关性和人表皮生长因子受体 2（HER2）表达。
设计、地点和参与者：对 100 例接受根治性膀胱切除术（RC）治疗的 UCB 患者的连续血液样本进行了研究，以检测 CTC 的存在（CellSearch 系统）及其 HER2 表达状态（免疫组织化学）。使用荧光原位杂交分析相应的原发性肿瘤和淋巴结转移的 HER2 表达。
术前采集血液样本。患者接受 RC 加淋巴结切除术。
根据 CTC 状态评估结果。比较 CTC 与相应原发性肿瘤和淋巴结转移的 HER2 表达。
100 例非转移性 UCB 患者中有 23 例（23%）检测到 CTC（中位数：1；范围：1-100）。CTC 的存在、数量和 HER2 状态与临床病理特征无关。CTC 阳性患者的疾病复发、癌症特异性和总死亡率风险显著升高（p 值：≤0.001）。在调整了标准临床病理特征的影响后，CTC 阳性仍然是所有终点的独立预测因素（风险比：4.6、5.2 和 3.5，分别；p 值≤0.003）。在 22 例患者中的 3 例（14%）的 CTC 中出现强烈的 HER2 阳性。在 23%的病例中，CTC 上的 HER2 表达与原发性肿瘤的 HER2 基因扩增状态不一致，但在所有 CTC 阳性病例中（100%），CTC、原发性肿瘤和淋巴结转移之间一致。该研究受到样本量的限制。
接受 RC 治疗的临床非转移性 UCB 患者中，近四分之一的患者术前即可检测到 CTC，是早期疾病复发、癌症特异性和总死亡率的有力预测指标。因此，CTC 可能作为多模态治疗的指征。CTC 的分子特征分析可作为未来临床试验中指导个体化靶向治疗的液体活检。
