Abstract IA06: A urine assay to triage patients with hematuria for cystoscopy

Abstract

Abstract Objectives: To assess the accuracy of a previously developed molecular assay to detect bladder cancer in a large prospective cohort of patients referred for hematuria. Design, Setting and Participants: 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. Main outcome measures: Primary endpoint was the model performance to detect the presence of urothelial cancer, as indicated by the area under the receiver operating characteristic (ROC) curve (AUC). Secondary endpoints were the sensitivity, specificity, and negative predictive value (NPV) of the optimal diagnostic model. 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 “cystoscopy for all.” 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 53% reduction in cystoscopies. Conclusions: The urine test detects urothelial cancer with a very high accuracy and is ready for clinical implementation. Citation Format: Kim E.M. van Kessel, Joep J. de Jong, Angelique C.J. Ziel-van der Made, Hossain Roshani, Stefan M. Haensel, Josien H. Wolterbeek, Egbert R. Boevé, Eric H.G.M. Oomens, Niels J. van Casteren, Manuel Krispin, Joost L. Boormans, Ewout W. Steyerberg, Wim van Criekinge, Ellen C. Zwarthoff. A urine assay to triage patients with hematuria for cystoscopy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA06.