Riethdorf Sabine, Soave Armin, Rink Michael
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Transl Androl Urol. 2017 Dec;6(6):1090-1110. doi: 10.21037/tau.2017.09.16.
Urothelial carcinoma of the bladder (UCB) is a complex disease, which is associated with highly aggressive tumor biologic behavior, especially in patients with muscle-invasive and advanced tumors. Despite multimodal therapy options including surgery, radiotherapy and chemotherapy, UCB patients frequently suffer from poor clinical outcome. Indeed, the potential of diverse opportunities for modern targeted therapies is not sufficiently elucidated in UCB yet. To improve the suboptimal treatment situation in UCB, biomarkers are urgently needed that help detecting minimal residual disease (MRD), predicting therapy response and subsequently prognosis as well as enabling patient stratification for further therapies and therapy monitoring, respectively. To date, decision making regarding treatment planning is mainly based on histopathologic evaluation of biopsies predominantly derived from the primary tumors and on clinical staging. However, both methods are imperfect for sufficient outcome prediction. During disease progression, individual disseminated tumor cells and consecutively metastases can acquire characteristics that do not match those of the corresponding primary tumors, and often are only hardly assessable for further evaluation. Therefore, during recent years, strong efforts were directed to establish non-invasive biomarkers from liquid biopsies. Urine cytology and serum tumor markers have been established for diagnostic purposes, but are still insufficient as universal biomarkers for decision-making and treatment of UCB patients. To date, the clinical relevance of various newly established blood-based biomarkers comprising circulating tumor cells (CTCs), circulating cell-free nucleic acids or tumor-educated platelets is being tested in cancer patients. In this review we summarize the current state and clinical application of CTCs and circulating cell-free tumor DNA originating from blood as biomarkers in patients with different UCB stages.
膀胱尿路上皮癌（UCB）是一种复杂的疾病，与高度侵袭性的肿瘤生物学行为相关，尤其是在肌肉浸润性和晚期肿瘤患者中。尽管有包括手术、放疗和化疗在内的多模式治疗选择，但UCB患者的临床结局往往较差。事实上，现代靶向治疗的各种潜在机会在UCB中尚未得到充分阐明。为了改善UCB中次优的治疗状况，迫切需要生物标志物来帮助检测微小残留病（MRD）、预测治疗反应及随后的预后，以及分别实现患者分层以进行进一步治疗和治疗监测。迄今为止，治疗计划的决策主要基于主要来自原发性肿瘤的活检组织的组织病理学评估和临床分期。然而，这两种方法在充分预测结局方面都不完善。在疾病进展过程中，单个播散的肿瘤细胞以及随后的转移灶可能获得与相应原发性肿瘤不匹配的特征，并且通常很难进行进一步评估。因此，近年来，人们大力致力于从液体活检中建立非侵入性生物标志物。尿细胞学和血清肿瘤标志物已用于诊断目的，但作为UCB患者决策和治疗的通用生物标志物仍不足。迄今为止，包括循环肿瘤细胞（CTC）、循环游离核酸或肿瘤衍生血小板在内的各种新建立的基于血液的生物标志物的临床相关性正在癌症患者中进行测试。在本综述中，我们总结了不同UCB分期患者中源自血液的CTC和循环游离肿瘤DNA作为生物标志物的现状和临床应用。
