Biomarkers for bladder cancer diagnosis and surveillance: A comprehensive review

Bladder cancer (BC) ranks as the sixth most prevalent cancer in the world, with a steady rise in its incidence and prevalence, and is accompanied by a high morbidity and mortality. BC is a complex disease with several molecular and pathological pathways, thus reflecting different behaviors depending on the clinical staging of the tumor and molecular type. Diagnosis and monitoring of BC is mainly performed by invasive tests, namely periodic cystoscopies; this procedure, although a reliable method, is highly uncomfortable for the patient and it is not exempt of comorbidities. Currently, there is no formal indication for the use of molecular biomarkers in clinical practice, even though there are several tests available. There is an imperative need for a clinical non-invasive testing for early detection, disease monitoring, and treatment response in BC. In this review, we aim to assess and compare different tests based on molecular biomarkers and evaluate their potential role as new molecules for bladder cancer diagnosis, follow-up, and treatment response monitoring.This research was funded by FCT ("Portuguese Foundation for Science and Technology") through a PhD grant to R.B. (SFRH/BD/111321/2015). Further funding was obtained from the project "Advancing cancer research: from basic knowledge to application" NORTE-01-0145-FEDER-000029: "Projetos Estruturados de I & D & I," funded by Norte 2020 - Programa Operacional Regional do Norte. This article is also a result of the project PTDC/MED-ONC/31438/2017 (The Other Faces of Telomerase: Looking beyond Tumor Immortalization), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), COMPETE 2020?Operacional Programme for Competitiveness and Internationalisation (POCI) and by Portuguese funds through FCT. The APC was funded by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalisation?COMPETE 2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM