Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer

Abstract

Background: A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC.

Objective: To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC.

Design, setting, and participants: Voided precystoscopy urine samples were prospectively collected at 22 sites. Xpert, cytology, and UroVysion were performed. If cystoscopy was suspicious for BC, a histologic examination was performed. Additionally, technical validation was performed and specificity was determined in patients without a history or clinical evidence of BC.

Outcome measurements and statistical analysis: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion.

Results and limitations: Of the eligible patients, 239 with a history of BC had results for all assays. The mean age was 71 yr; 190 patients were male, 53 never smoked, and 64% had previous intravesical immunotherapy (35%) or chemotherapy (29%). Forty-three cases of recurrences occurred. Xpert had overall SN of 74% (95% confidence interval [CI]: 60-85) and 83% (95% CI: 64-93) for high-grade (HG) tumors. The NPV was 93% (95% CI: 89-96) overall and 98% (95% CI: 94-99) for HG tumors. Specificity was 80% (95% CI: 73-85). Xpert SN and NPV were superior to those of cytology and UroVysion. Specificity in non-BC individuals (n=508) was 95% (95% CI: 93-97).

Conclusions: Xpert has an improved NPV compared with UroVysion and cytology in patients under follow-up for BC. It represents a promising tool for excluding BC in these patients, reducing the need for cystoscopy.

Patient summary: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help optimize the follow-up of recurrent bladder cancer patients.

Keywords: Bladder cancer; Cystoscopy; Diagnostic test; Non-muscle-invasive bladder cancer; Recurrence; Sensitivity; Specificity; Urine test; mRNA.