Department of Medical Oncology, University of Bern, Bern, Switzerland.
Department of Urology, University of Bern, 3010, Bern, Switzerland.
World J Urol. 2019 Sep;37(9):1759-1765. doi: 10.1007/s00345-018-2544-8. Epub 2018 Nov 3.
For 40 years cisplatin-based chemotherapy has been administered to patients with muscle-invasive bladder cancer (MIBC). The best evidence of its efficacy is found in the context of neoadjuvant chemotherapy (NAC). However, the benefit to the patient is modest, with an improvement in 5-year overall survival of only 5-8%. Approximately 60% of patients still have muscle-invasive disease at cystectomy despite NAC. Selecting patients based on the likelihood of response appears to be a promising strategy to improve on this modest benefit. To realize this promise, researchers are investigating biomarkers for identifying responders and non-responders prior to NAC.
In this review, we discuss a number of tissue- and liquid-based biomarkers associated with the response to NAC.
We elaborate biomarkers at the methylation, DNA, RNA and protein levels and give their current status in clinical trials and/or their implementation in daily clinical practice. In particular, detection of alterations in DNA damage repair pathways as well as molecular subtypes seems to be a promising method for identifying responders to NAC. Furthermore, we illustrate liquid-based biomarkers. Circulating tumor DNA (ctDNA) in patient blood and urine appear to offer an elegant way for biological characterization of MIBC. Recent data show that the presence of ctDNA is limited in patients with localized MIBC being considered for NAC. At this disease stage, ctDNA in patient urine may be more promising for the genomic characterization of MIBC. However, ctDNA in blood or urine has not yet been rigorously investigated in this clinical context.
40 年来，顺铂为基础的化疗已被用于肌层浸润性膀胱癌（MIBC）患者。其疗效的最佳证据见于新辅助化疗（NAC）的背景下。然而，患者获益甚微，5 年总生存率仅提高了 5-8%。尽管接受了 NAC，仍有约 60%的患者在膀胱切除术后仍有肌层浸润性疾病。根据对治疗的反应可能性来选择患者，似乎是提高这一适度获益的一种有前途的策略。为了实现这一承诺，研究人员正在研究生物标志物，以便在 NAC 前识别出应答者和无应答者。
在这篇综述中，我们讨论了一些与 NAC 反应相关的组织和液体生物标志物。
我们详细阐述了在甲基化、DNA、RNA 和蛋白质水平上的生物标志物，并介绍了它们在临床试验中的现状和/或在日常临床实践中的应用。特别是，检测 DNA 损伤修复途径以及分子亚型的改变似乎是识别 NAC 应答者的一种很有前途的方法。此外，我们还介绍了液体生物标志物。患者血液和尿液中的循环肿瘤 DNA（ctDNA）似乎为 MIBC 的生物学特征提供了一种优雅的方法。最近的数据表明，在考虑接受 NAC 的局限性 MIBC 患者中，ctDNA 的存在是有限的。在这个疾病阶段，患者尿液中的 ctDNA 可能更有希望用于 MIBC 的基因组特征分析。然而，在这种临床背景下，血液或尿液中的 ctDNA 尚未得到严格研究。
