Presentation Authors: Kim van Kessel, Joep Jacobus de Jong, Angelique Ziel-van der Made, Rotterdam, Netherlands, Hossain Roshani, The Hague, Netherlands, Stefan Haensel, Josien Wolterbeek, Rotterdam, Netherlands, Egbert Boevé, Rotterdam, Netherlands Antilles, Eric Oomens, Breda, Netherlands, Niels van Casteren, Rotterdam, Netherlands, Manuel Krispin, San Francisco, CA, Joost Boormans, Ewout Steyerberg, Rotterdam, Netherlands, Wim van Criekinge*, Ghent, Belgium, Ellen Zwarthoff, Rotterdam, Netherlands
Introduction: The prevalence of hematuria in the general population is estimated to be 9-18%. Cystoscopy is recommended to rule out the presence of a bladder tumor. Given the low incidence of bladder cancer and the invasive nature of cystoscopy, a urine test to rule out patients for cystoscopy is an unmet need. Here, we validate a sensitive urine assay in a large prospective cohort of patients presenting with hematuria.
Methods: A urine sample was collected prior to cystoscopy and mutation/methylation status of 6 genes was determined in DNA from urinary cells and combined with age. This existing diagnostic model was validated on this cohort and optimized using logistic regression. Clinical usefulness was determined by the net benefit approach.
Results: In 838 patients, the mutation/methylation status could be determined for all genes. Urothelial cancer was observed in 112 patients (98/457 in the gross and 14/381 in the microscopic hematuria group) Application of the existing model resulted in an AUC of 0.93. Combining the assay with the type of hematuria resulted in the final optimal model with an AUC of 0.96 (96% sensitivity, 73% specificity, 99% negative predictive value). The assay also detected all six upper tract urothelial tumors that are not visible by cystoscopy. Net benefit analysis showed that the urine test should be preferred over &[prime]cystoscopy for all&[prime]. Application of the optimal model on patients whose biomarker status was incomplete, resulted in the identification of 5 additional tumors. Implementing the urine test as a triage tool could lead to a 63% reduction in cystoscopies.
Conclusions: The urine test detects urothelial cancer in hematuria patients with high accuracy. It appears a simple selection tool, in particular for patients with microscopic hematuria.
Source of Funding: This study was funded by MDxHealth and powered by Health Holland, Top Sector Life Sciences & Health (https://www.health-holland.com)