Upper Tract Urothelial Carcinoma: An Update on Current Diagnostic Modalities and Emerging Biomarkers

Introduction: Upper tract urothelial carcinoma is a rare disease with variable prognosis depending on the stage and grade at diagnosis. Current modalities are far from perfect in diagnosis and risk stratification. In this setting, there is an urgent need for diagnostic and prognostic biomarkers to overcome these limitations. Methods: We carried out a narrative review of the literature searching for research articles on diagnostic and prognostic biomarkers for upper tract urothelial carcinoma (UC) and underlined the limitations of current diagnostic modalities. Results: CT urogram (CTU) is the imaging modality of choice in suspected upper tract UC with sensitivity and specificity exceeding 90% but with limitations in smaller lesions. Urine cytology has an excellent specificity for high-grade UC but is limited by low sensitivity leading to a high number of diagnostic ureteroscopies with significant associated risks. Adjuncts such as Fluorescence In Situ Hybridization (FISH) technology and urine DNA methylation markers have shown promising results but need further validation in large cohorts of upper tract UC. Finally, circulation tumour DNA (ctDNA) is a novel approach with great potential in risk stratification and monitoring of minimal residual disease post radical surgery; however, larger prospective studies are required to validate its role similarly to the recent bladder UC trials. Conclusions: There is an urgent need for non-invasive biomarkers that can reliably replace diagnostic ureteroscopies, identify high-risk/invasive disease and select patients for radical surgery or kidney sparing procedures.