Editorial Comment: Identification of a Highly Sensitive Combination of Urinary Protein Biomarkers for the Detection of High-Grade Bladder Cancer
Year: 2025
Type: editorial
Abstract: The study by Bouchard et al1 “Identification of a highly sensitive combination of urinary protein biomarkers for the detection of high-grade bladder cancer” uses mass spectrometry-based proteomics to develop and validate a combination of 4 proteins—Complement Factor H (CFH), Fibrinogen β (FGB), Alpha-34 2-macroglobulin (A2M), and Pancreatic Alpha-amylase (AMY2A) for detection of bladder cancer. A sample was considered positive if at least 2 of 4 markers exceeded their threshold (for CFH, FGB, A2M) or fell below it (for AMY2A). This combinatorial rule provided 100% sensitivity for identifying high-grade tumors across all stages. Specificity reached 80% in patients with no history of bladder cancer and 73% for patients with bladder cancer in remission. The overall study had 201 patients between discovery and validation, and the cohorts lacked specificity such as evaluation of this marker in patients with hematuria as opposed to general benign conditions. One of the main limitations of urine-based tumor markers is a low positive predictive value such that actionability of a positive result is not clear. Because this marker panel had lower specificity in patients with bladder cancer, further research is needed to determine how it performs in patients with repeated instrumentation and intravesical therapies as seen in patients with bladder cancer. There are multiple obstacles in marker development that lead to an arduous process from discovery to clinical application. Multiple markers using proteins, DNA, RNA, methylation, and combinations have been developed, and yet, guidelines still have a limited role for urine markers in clinical use. The new AUA and Society for Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction recently updated the microhematuria guidelines and provide guidance regarding options for use of certain urine-based tumor markers in patients with intermediate risk stratification.2 In surveillance, the role is still limited to adjudicating atypical cytology and response to bacille calmette guerin. Urine markers need to demonstrate clinical utility to expand their role in managing patients with hematuria and bladder cancer. The final obstacle is the ever growing challenge with obtaining reimbursement since there are ongoing constraints on payment by Medicare and insurance companies.3
Source: JU Open Plus
Author: Yair Lotan
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4417154805