Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review.

Rui Batista,Valdemar Máximo,Nuno Vinagre,João Vinagre,Paula Soares,Sara Meireles,Ricardo Leão,Hugo Prazeres

doi:10.3390/diagnostics10010039

Abstract

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.

Highlights

Bladder cancer (BC) is the sixth most prevalent cancer in both genders and the fourth in males worldwide
The highest levels of methylation were associated with recurrence and with a greater likelihood of receiving radical cystectomy [86], further enhancing the usefulness of this type of biomarker in disease follow-up and diagnosis
A study evaluating the plasma levels of the Long-noncoding RNAs (lncRNAs) TUC338 in patients with BC when compared with healthy controls, observed that lncRNA TUC338 was significantly upregulated in early-stages

Summary

Introduction

Bladder cancer (BC) is the sixth most prevalent cancer in both genders and the fourth in males worldwide (incidence of 9.6 and 2.4 per 100,000 in men and women, respectively; age-standardized rates). In 2018, more than half a million people were diagnosed with BC and 200,000 died from the disease. The region with the highest incidence of this cancer was Southern Europe with 15.2 per 100,000 and North Africa with the highest mortality rate of 4.4 per 100,000. The mortality rate of BC in 2018 was 1.9 in 100,000 [1,2]. The majority of BC arises from epithelial cells and approximately 90% are urothelial tumors, with squamous and glandular-type tumors as less frequent histologic subtypes; more rarely, bladder tumors arise from mesenchymal cells [3]. Christensen and collaborators [4]

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