Abrahamsson Johan, Aaltonen Kristina, Engilbertsson Helgi, Liedberg Fredrik, Patschan Oliver, Rydén Lisa, Sjödahl Gottfrid, Gudjonsson Sigurdur
Department of Urology, Skåne University Hospital, Lund, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden.
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Urol Oncol. 2017 Oct;35(10):606.e9-606.e16. doi: 10.1016/j.urolonc.2017.05.021. Epub 2017 Jul 1.
There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells.
To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer.
DESIGN, SETTING, AND PARTICIPANTS: Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients.
Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival.
CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6-21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005-7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM.
CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen-based CTC detection methods.
目前临床上尚无能够检测尿路上皮肿瘤细胞早期全身播散的方法。
评估循环肿瘤细胞（CTC）检测作为晚期膀胱癌播散性疾病生物标志物的价值。
设计、地点和参与者：2013年3月至2015年10月，88例患者前瞻性纳入本研究：78例计划行根治性膀胱切除术（RC）±围手术期化疗，10例接受姑息性化疗。通过检测409例独立队列患者膀胱切除术中获得的原发肿瘤上皮细胞粘附分子（EpCAM）的表达，进一步评估CellSearch CTC检测。
检测CTC的存在与肿瘤分期、淋巴结转移、[18F] -氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）上的转移性疾病以及癌症特异性生存率和无进展生存率之间的关联。
88例患者中有17例（19%）检测到CTC。在61例行FDG-PET计算机断层扫描（CT）的患者中，发现放射学上的转移性疾病与CTC的存在有统计学意义的关联，但PET-CT结果正常者无此关联（12/35 [34%]对2/26 [8%]，P = 0.014）。中位随访时间为16.5个月（95%CI：9.6 - 21.4），在接受RC联合或不联合围手术期化疗的患者中（n = 75），CTC的存在与疾病进展风险增加相关（P = 0.049）。多因素分析校正临床肿瘤分期、临床淋巴结状态和年龄后显示，CTC是疾病进展的独立标志物（n = 75；风险比 = 2.78；95%CI：1.005 - 7.69；P = 0.049），但不是癌症特异性死亡的独立标志物（P = 0.596）。在409例膀胱切除患者中，超过392例（96%）膀胱肿瘤表达EpCAM。
晚期尿路上皮肿瘤患者中19%存在CTC，且与FDG-PET-CT上的转移性疾病以及RC后疾病进展风险增加相关。相当一部分尿路上皮癌细胞确实表达EpCAM，因此可使用基于EpCAM抗原的CTC检测方法进行识别。
