Sugeeta Sukumar S, Sharma Anand, Ng Kenrick, Nayak Arvind, Vasdev Nikhil
Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, United Kingdom.
Department of Urology and Surgery, Lister Hospital, East and North Herts NHS Trust, Stevenage, United Kingdom.
Front Surg. 2021 Sep 28;8:735868. doi: 10.3389/fsurg.2021.735868. eCollection 2021.
This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays. Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade. Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms "bladder cancer," "non-muscle invasive bladder cancer," and "urine biomarkers" with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated. Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use. Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.
这是一篇叙述性综述,旨在总结和描述非肌层浸润性膀胱癌(NMIBC)监测中的尿液生物标志物。它总结了美国食品药品监督管理局(FDA)批准的蛋白质生物标志物以及利用基因、表观遗传和外泌体标志物的新兴生物标志物。我们讨论了现有检测方法目前存在的局限性。当前指南建议在诊断和监测中结合膀胱镜检查、影像学检查和尿液细胞学检查。虽然细胞学检查具有较高的特异性,但它受到低敏感性的限制,尤其是在低级别肿瘤中。有六种FDA批准的用于膀胱癌诊断和监测的尿液检测方法。它们已被证明与细胞学检查和膀胱镜检查一起使用时可提高敏感性和特异性,但与细胞学检查相比特异性较低,并且在良性疾病中经常出现假阳性。在过去十年中,实验室技术的最新进展使得基于RNA、DNA的标志物以及细胞外囊泡得以应用。我们使用PubMed/Medline搜索引擎以及谷歌学术,使用“膀胱癌”“非肌层浸润性膀胱癌”和“尿液生物标志物”等术语进行在线搜索,并筛选截至2021年5月发表的英文文章。整理了有助于生物标志物开发的系统评价以及临床试验或观察性研究的原始数据。鉴定出的生物标志物分为FDA批准的分子生物标志物、蛋白质生物标志物和基因相关生物标志物,并通过表格总结了每个标志物的研究结果及最相关的研究。所进行的研究主要是回顾性的。由于处于开发的早期阶段,对于最近开发的生物标志物仅进行了少数前瞻性研究,并且可用的荟萃分析有限。因此,仍需要对这些标志物进行详细评估以确定其临床用途。膀胱癌分析方法的进步推动了对尿液细胞学辅助的非侵入性液体生物标志物的研究。由于单独使用时存在局限性,效果不佳,因此需要进一步的大型前瞻性研究来确定其在临床环境中的可行性。在当前的大流行情况下,除了降低成本和提高准确性外,在诊断和监测中需要生物标志物来应对膀胱镜检查延迟至关重要。因此,需要进行直接比较的临床试验以改善患者护理。