Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review

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.

tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5′-tRF-LysCTT Results in Disease Early Progression and Patients’ Poor Treatment Outcome

“…Currently, several FDA approved tests have been developed for the non-invasive diagnosis and surveillance of BlCa, including NMP22, BTA-TRAK, UroVysion and ImmunoCyt/uCyt + tests. Although they surpass the current limitations of urine cytology, none of them present promising sensitivity and specificity values able either to replace cystoscopy in the diagnostic and monitoring setting or to provide accurate disease prognosis and patients-risk stratification [54]. The identification of the molecular background of bladder tumors could offer an alternative approach to improve BlCa management.…”

Hot Spot TERT Promoter Mutations Are Rare in Sporadic Pancreatic Neuroendocrine Neoplasms and Associated with Telomere Length and Epigenetic Expression Patterns

“…Several studies of other tumor types identified that TPMs predict worse patient outcome, e.g., [ 17 , 28 , 29 , 30 ]. TPMs are not only prognostic factors, but also predictors of radiotherapy resistance in gliomas [ 31 ] and biomarkers for clinical non-invasive testing of bladder cancer diagnosis and surveillance [ 32 ]. Targeting of non-coding TPMs remains an unresolved challenge, but recent findings raise the possibility that telomerase inhibition currently investigated in clinical trials might be an effective intervention in cells with TPM [ 5 , 33 ].…”

Comparison of Pteridine Normalization Methods in Urine for Detection of Bladder Cancer

“…The complexity and interrelationships of the metabolic pathways involved in cancer biology necessitate specific and sensitive markers for capturing clinically relevant changes in multiple metabolic pathways of carcinogenesis and tumor behavior. The rapidly changing consignment of metabolomics research represents a promising approach to developing effective cancer diagnosis and treatment strategies by monitoring fluctuations in the levels of certain metabolites in cells, tissues and biological fluids and establishing clinically useful diagnostic computational models [1].…”

“…They differ in their sensitivity, specificity and the methods used to determine them. However, only a small number of the markers tested are used in routine diagnosis [1]. The most common diagnostic tests performed for bladder cancer include urine cytology [6,7], hematuria detection [8][9][10], bladder tumor antigen detection (BTA) [7,[11][12][13], the UroVysion test [14,15] and nuclear matrix protein 22 detection [16][17][18].…”