Biomarkers for precision medicine in bladder cancer

Bladder cancer (BC) is classified as non-muscle-invasive BC (NMIBC) or muscle-invasive BC (MIBC). Because the recurrence and mortality rates of BC are high, suitable biomarkers for early detection, evaluation of prognosis, and surveillance of drug responses are needed. Urinary markers simplify surveillance schedules and improve early detection of tumors, especially in NMIBC. Various markers have been identified at DNA, RNA, and protein levels with different sensitivities and specificities. Several biomarkers show a higher sensitivity than urinary cytology, but they are not accurate enough to replace it. In terms of prediction of clinical outcome and treatment response of BC, conventional clinical and pathological parameters are widely used, but the predictive ability of these parameters is limited; therefore, molecular biomarkers in this field are strongly desired. Molecular profiling using fluid and tissue is becoming more feasible with recent developments in next-generation sequencing technologies. Currently, these profiling methods are beginning to be used for early detection, prediction of prognosis, and drug sensitivity. Furthermore, several groups used transcriptome profiling to classify MIBC into various distinct subtypes, showing distinct clinical behaviors and responses to chemotherapy and immune checkpoint inhibitors. The aim of this review is to provide a summary of the most relevant biomarkers that have been investigated as diagnostic and prognostic indicators of BC.