Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study

Purpose: Urothelial carcinoma is associated with a high rate of recurrence. Guidelines recommend rigorous, regular surveillance programs that are invasive and expensive. This study describes a noninvasive urine test with sufficient sensitivity to rule out recurrent urothelial carcinoma, thereby reducing invasive diagnostic evaluations without compromising patient care. Methods and Materials: A total of 1,036 urine samples were prospectively collected from 763 patients undergoing routine surveillance for recurrent urothelial carcinoma of the bladder. The purpose was to develop and validate a test with combined high sensitivity and high negative predictive value. Cxbladder Monitor combines gene expression, clinical and patient data, and it is designed to rule out the presence of recurrent urothelial carcinoma. Results: Cxbladder Monitor showed an internally validated sensitivity of 0.93 with a negative predictive value of 0.97 and a test negative rate of 0.34. Sensitivity was 0.95 for recurrent disease with a high risk of progression (all high grade disease and low grade, stage T1 or greater disease) compared with 0.86 for low grade Ta disease. Subgroup analyses indicated that diagnostic performance was not significantly different in different age groups, or by gender or tumor stage. Sensitivity was not affected by adjuvant bacillus Calmette-Guerin treatment within the last 6 months. False-negative findings were reported in fewer than 1.5% of all samples collected. Conclusions: The Cxbladder Monitor test offers combined high sensitivity and high negative predictive value to rule out urothelial carcinoma. This test has clinical utility as a confirmatory negative adjunct to cystoscopy, potentially justifying the postponement/avoidance of cystoscopic investigations to monitor recurrence in patients.