Longitudinal Follow-up and Performance Validation of a mRNA-based Urine Test (Xpert® Bladder Cancer Monitor) for surveillance in Non-Muscle Invasive Bladder Cancer Patients.

PURPOSE: Frequent recurrences and the potential for progression of non-muscle-invasive bladder cancer (NMIBC) demand close surveillance. This prospective study evaluated the performance of Xpert Bladder Cancer Monitor (Xpert) test as a predictor of tumor recurrence.

PATIENTS AND METHODS: Patients (n=429) undergoing surveillance for NMIBC underwent Xpert, cytology, and UroVysion testing. Patients with a positive Xpert and a negative cystoscopy (positive-negative group = PN; n=66) and control group of double negative patients (negative Xpert and cystoscopy results = NN) were followed for 12 months (+/- 90 days).

RESULTS: Histology-confirmed recurrences were detected in 58 patients (13.5%). Xpert had an overall sensitivity of 60.3% and specificity of 76.5%. The sensitivity for high grade (HG) cancer was 87% with a negative predictive value (NPV) of 99%. Urine cytology showed an overall sensitivity of 23.2% (47.6% sensitivity for HG) and specificity of 88.3%. In the group of PN patients, 32% (n=21) developed a recurrence within 12 months, 11 of which were HG tumors. In the NN control group, 14% (n= 9) developed a recurrence and only 2 were HG tumors. The Hazard Ratio for developing recurrence in the PN group was 2.68 for all tumors and 6.84 for HG cancer.

CONCLUSIONS: The Xpert test has a high sensitivity for detecting the recurrence of cancer and a high negative predictive value for excluding HG cancer. In addition, the data suggest that patients with a positive Xpert assay in setting of negative cystoscopy are at high risk for recurrence and need close surveillance.