Department of Urology, University Hospital Tuebingen, Hoppe-Seyler-Straße 3, 72076, Tuebingen, Germany.
World J Urol. 2019 Sep;37(9):1741-1749. doi: 10.1007/s00345-018-2505-2. Epub 2018 Oct 3.
Diagnosis and follow-up in patients with non-muscle invasive bladder cancer (NMIBC) rely on cystoscopy and urine cytology. The aim of this review paper is to give an update on urinary biomarkers and their diagnosis and surveillance potential. Besides FDA-approved markers, recent approaches like DNA methylation assays, mRNA gene expression assays and cell-free DNA (cfDNA) are evaluated to assess whether replacing cystoscopy with urine markers is a potential scenario for the future.
We performed a non-systematic review of current literature without time period restriction using the National Library of Medicine database ( http://ww.pubmed.gov ). The search included the following key words in different combinations: "urothelial carcinoma", "urinary marker", "hematuria", "cytology" and "bladder cancer". Further, references were extracted from identified articles. The results were evaluated regarding their clinical relevance and study quality.
Currently, replacing cystoscopy with available urine markers is not recommended by international guidelines. For FDA-approved markers, prospective randomized trials are lacking. Newer approaches focusing on molecular, genomic and transcriptomic aberrations are promising with good accuracies. Furthermore, these assays may provide additional molecular information to guide individualized surveillance strategies and therapy. Currently ongoing prospective trials will determine if cystoscopy reduction is feasible.
Urinary markers represent a non-invasive approach for molecular characterization of the disease. Although fully replacing cystoscopy seems unrealistic in the near future, enhancing the current gold standard by additional molecular information is feasible. A reliable classification and differentiation between aggressive and nonaggressive tumors by applying DNA, mRNA, and cfDNA assays may change surveillance to help reduce cystoscopies.
非肌层浸润性膀胱癌(NMIBC)患者的诊断和随访依赖于膀胱镜检查和尿液细胞学检查。本文旨在介绍尿液生物标志物及其诊断和监测潜力的最新进展。除了获得 FDA 批准的标志物外,还评估了最近的方法,如 DNA 甲基化测定、mRNA 基因表达测定和游离 DNA(cfDNA),以评估是否可以用尿液标志物替代膀胱镜检查作为未来的潜在方案。
我们在没有时间限制的情况下,使用美国国立医学图书馆数据库(http://www.pubmed.gov)进行了非系统性文献回顾。搜索包括以下关键词的不同组合:“尿路上皮癌”、“尿液标志物”、“血尿”、“细胞学”和“膀胱癌”。此外,还从已确定的文章中提取参考文献。根据其临床相关性和研究质量对结果进行了评估。
目前,国际指南不建议用现有的尿液标志物替代膀胱镜检查。对于获得 FDA 批准的标志物,缺乏前瞻性随机试验。关注分子、基因组和转录组异常的新方法具有良好的准确性,前景广阔。此外,这些检测方法可以提供额外的分子信息,以指导个体化的监测策略和治疗。目前正在进行的前瞻性试验将确定是否可以减少膀胱镜检查。
尿液标志物代表了一种用于疾病分子特征分析的非侵入性方法。虽然在不久的将来完全替代膀胱镜检查似乎不太现实,但通过附加分子信息增强当前的金标准是可行的。通过应用 DNA、mRNA 和 cfDNA 检测方法对侵袭性和非侵袭性肿瘤进行可靠的分类和区分,可能会改变监测方法,有助于减少膀胱镜检查。