Emerging biomarkers for the diagnosis and monitoring of urothelial carcinoma

Urothelial carcinoma (UC) arises extensively from the renal pelvis, ureter, urinary bladder, and urethra. UC represents a clinical and social challenge because of its incidence, post-treatment recurrence rate, and prognosis. Combinations of urine cytology, cystoscopy, and conventional imaging such as computed tomography are currently used for diagnosis and monitoring modalities of UC. Both the poor diagnostic accuracy of urine cytology and poor cost performance of cystoscopy and conventional imaging modalities emphasize the urgent need for advancement in clinical guidance for UC. Urine- and blood-based biomarkers for detection of UC of the bladder and upper urinary tract represent a considerable research area. Biomarkers can help to improve UC diagnosis with the aim of replacing cystoscopy and other imaging examinations in future and may enable individualizing risk stratification regarding therapy and follow-up. Over the decades, numerous studies have focused on the potential application of biomarkers for UC, including urine, circulating tumor DNA, RNAs, proteins, and extracellular vesicles. Although some biomarkers such as ImmunoCyt/uCyt+, UroVysion, NMP-22, bladder tumor antigen, CxBladder, and Xpert Bladder Cancer are currently available in clinical practice, few biomarkers achieve high sensitivity and specificity. Emerging biomarkers are continuously developed and reported in medical journals. However, there is a significant lack on following external validation using different cohorts. The positive results are needed to be confirmed by more studies with large-scale cohorts and long follow-up periods to prove the true value of novel biomarkers, followed by their adoption in clinical practice. The present paper provides an overview of the evidence based on high-impact studies regarding urine- and blood-based biomarkers and their clinical applications in bladder cancer and upper tract UC.