Non-Invasive Biomarkers in the Diagnosis of Upper Urinary Tract Urothelial Carcinoma—A Systematic Review

SIMPLE SUMMARY: Laboratory and imaging tests as well as endoscopic procedures are standard diagnostic tools for the diagnosis of upper urinary tract urothelial carcinoma. We aimed to determine the effectiveness of non-invasive urinary and blodd-based tests in the diagnosis of urothelial carcinoma of upper urinary tract. Among 10,084 screened publications, 25 were eligible and included in the analysis. Most of them were conducted on small samples of patients and the control groups were heterogenous. The test used in the largest number of studies was voided urinary cytology, which has poor sensitivity with favorable specificity. Fluorescence in situ hybridization in diagnostic cytology showed higher sensitivity with equally good specificity. There were also studies on the use of tests known to diagnose bladder cancer such as NMP22, uCYT or BTA test. Other urine or blood tests have been the subject of only isolated studies, with varying results. To conclude, currently there is a lack of high-quality data that could confirm good effectiveness of non-invasive tests used in the diagnosis of upper urinary tract urothelial carcinoma. ABSTRACT: Beyond laboratory, imaging and endoscopic procedures, new diagnostic tools are increasingly being sought for the diagnosis of upper urinary tract urothelial carcinoma (UTUC), especially those that are non-invasive. In this systematic review, we aimed to determine the effectiveness of non-invasive tests in the diagnosis of UTUC. PubMed and Embase electronic databases were searched to identify studies assessing effectiveness of non-invasive tests in the primary diagnosis of UTUC. The study protocol was registered with PROSPERO (CRD42020216480). Among 10,084 screened publications, 25 were eligible and included in the analysis. Most of them were conducted on small samples of patients and the control groups were heterogenous. The test used in the largest number of studies was voided urinary cytology, which has poor sensitivity (11–71.1%) with favorable specificity (54–100%). Fluorescence in situ hybridization in diagnostic cytology showed higher sensitivity (35–85.7%) with equally good specificity (80–100%). There were also studies on the use of tests known to diagnose bladder cancer such as NMP22, uCYT or BTA test. Other urine or blood tests have been the subject of only isolated studies, with varying results. To conclude, currently there is a lack of high-quality data that could confirm good effectiveness of non-invasive tests used in the diagnosis of UTUC.