Kenrick Ng1, Arnulf Stenzl2, Anand Sharma3, Nikhil Vasdev4. 1. UCL Cancer Institute, London, United Kindom. 2. Department of Urology, Eberhard-Karls-University, Tübingen, Germany. 3. Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, United Kindom. 4. Hertfordshire and Bedfordshire Urological Cancer Centre, Lister Hospital, Stevenage, United Kindom; School of Life and Medical Sciences, University of Hertfordshire, United Kindom. Electronic address: nikhil.vasdev@nhs.net.
Abstract
AIM: This narrative review aims to describe established and emerging urinary biomarkers in the diagnosis and surveillance of non-muscle invasive bladder cancer. It provides a comprehensive account of classical, FDA-approved protein biomarkers and discusses their limitations. Further, we discuss the role that epigenetic, genetic, and exosomal markers can play to enhance sensitivity and specificity of the available tests. BACKGROUND: The initial diagnosis and surveillance of bladder cancer involves a combination of cystoscopy, upper urinary tract imaging, and urine cytology. Despite high specificity, cytology is limited by low sensitivity. There are currently 6 urinary assays approved by the FDA to enhance diagnosis and surveillance of bladder cancer. While these have improved diagnosis and surveillance when combined with cytology, these tests are still not sufficiently sensitive and false positives often occur in benign conditions which result in inflammation of the urinary tract. Advancements in laboratory techniques have produced significant advancements in epigenetic and genetic markers, as well as extracellular vesicles, with DNA- and RNA-based markers dominating the research in this area in recent years. METHODS: We identified relevant published data, 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" in combination with "urine biomarkers" and limited articles in English published up to February 2020. This review consolidated on all available narrative and systematic reviews published in the 5 years in this field, while also reviewing the original data of each clinical trial or observational study which led to the development of the biomarkers. CONCLUSION: The development of laboratory techniques and understanding urine-based biomarkers in BC has fuelled the use of noninvasive liquid-based biomarkers to complement urine cytology. Nonetheless, none are sufficiently effective when used in isolation, and cytology remains the gold standard in many practices. Future efforts will be focused on using these markers in combination as a predictive signature, and moving on to validating them for use in everyday clinical practice.
AIM: This narrative review aims to describe established and emerging urinary biomarkers in the diagnosis and surveillance of non-muscle invasive bladder cancer. It provides a comprehensive account of classical, FDA-approved protein biomarkers and discusses their limitations. Further, we discuss the role that epigenetic, genetic, and exosomal markers can play to enhance sensitivity and specificity of the available tests. BACKGROUND: The initial diagnosis and surveillance of bladder cancer involves a combination of cystoscopy, upper urinary tract imaging, and urine cytology. Despite high specificity, cytology is limited by low sensitivity. There are currently 6 urinary assays approved by the FDA to enhance diagnosis and surveillance of bladder cancer. While these have improved diagnosis and surveillance when combined with cytology, these tests are still not sufficiently sensitive and false positives often occur in benign conditions which result in inflammation of the urinary tract. Advancements in laboratory techniques have produced significant advancements in epigenetic and genetic markers, as well as extracellular vesicles, with DNA- and RNA-based markers dominating the research in this area in recent years. METHODS: We identified relevant published data, 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" in combination with "urine biomarkers" and limited articles in English published up to February 2020. This review consolidated on all available narrative and systematic reviews published in the 5 years in this field, while also reviewing the original data of each clinical trial or observational study which led to the development of the biomarkers. CONCLUSION: The development of laboratory techniques and understanding urine-based biomarkers in BC has fuelled the use of noninvasive liquid-based biomarkers to complement urine cytology. Nonetheless, none are sufficiently effective when used in isolation, and cytology remains the gold standard in many practices. Future efforts will be focused on using these markers in combination as a predictive signature, and moving on to validating them for use in everyday clinical practice.
Authors: Vittorio Fasulo; Marco Paciotti; Massimo Lazzeri; Roberto Contieri; Paolo Casale; Alberto Saita; Giovanni Lughezzani; Pietro Diana; Nicola Frego; Pier Paolo Avolio; Piergiuseppe Colombo; Grazia Maria Elefante; Giorgio Guazzoni; Nicolò Maria Buffi; Michael Bates; Rodolfo Hurle Journal: Front Oncol Date: 2022-01-27 Impact factor: 6.244