Diagnostic Accuracy of MCM5 for the Detection of Recurrence in Nonmuscle Invasive Bladder Cancer Followup: A Blinded, Prospective Cohort, Multicenter European Study

Abstract

Detection of MCM5 containing cells in urine has been shown to be indicative of the presence of a bladder tumor on primary diagnosis. In this study we evaluate diagnostic performance of ADXBLADDER in patients undergoing cystoscopic surveillance in nonmuscle invasive bladder cancer followup. Materials and Methods: A multicenter prospective blinded study was performed at 21 European centers with patients undergoing cystoscopy for nonmuscle invasive bladder cancer surveillance, diagnosed in the preceding 2 years. Urine was collected from all eligible patients and ADXBLADDER-MCM5 testing was performed. Performance characteristics were calculated by comparing MCM5 results to the outcome of cystoscopy plus pathological assessment. Results: Of 1,431 eligible patients enrolled 127 were diagnosed with a bladder cancer recurrence. The overall sensitivity for the ADXBLADDER-MCM5 test in detecting bladder cancer recurrence was 44.9% (95% CI 36.1e54) with a 75.6% sensitivity for nonpTaLG tumors (95% CI 59.7e87.6). Specificity was 71.1% (95% CI 68.5e73.5). The overall negative predictive value was 93% (95% CI 91.2e94.5). However, ADXBLADDER was able to rule out the presence of a nonpTaLG recurrent tumor with a negative predictive value of 99.0% (95% CI 98.2e99.5). No statistically significant differences in the performance of ADX-BLADDER were observed as a result of age or sex. Conclusions: This large blinded prospective study demonstrates that in the followup of patients with nonmuscle invasive bladder cancer ADXBLADDER is able to exclude the presence of the most aggressive tumors with a negative predictive value of 99%. These results indicate that ADXBLADDER could be incorporated in the followup strategy of nonmuscle invasive bladder cancer.

Assessment of Xpert Bladder Cancer Monitor test performance for the detection of recurrence during non-muscle invasive bladder cancer follow-up

“…Since then, other studies investigating the accuracy of this test for NMIBC surveillance have been published [11,[17][18][19], which, together with the current study, have confirmed the results of Pichler et al Limitations of our study include the small number of cytology tests analysed, limited due to a lack of available sample material. The percentage of recurrent tumours was also lower (8.8%) than that reported in other studies investigating Xpert BC Monitor accuracy in the follow-up of NMIBC (18.0-30.7%) [6,11,17,18], but similar to that reported in a large-scale study investigating another urinary test (N = 127/1431, 8.9%) [20]. Nevertheless, patients were unselected in our prospective study, reflecting real-life clinical settings.…”

Follow-up in non-muscle invasive bladder cancer: facts and future

“…This year the diagnostic accuracy of a novel test targeting MCM5, a DNA licensing factor and biomarker of cell proliferation, was published, the ADXBLADDER test (Arquer Diagnostics, Sunderland) [37]. It was a prospective, multicentric European study for the detection of recurrence after NMIBC in the preceding 2 years.…”

Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis

“…Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. All the studies included in the quantitative synthesis reported on the diagnostic value of UBTs for the detection of recurrence during surveillance: ten studies on Xpert bladder cancer [17][18][19][20][21][22][23][24][25][26], five studies on Bladder EpiCheck [26][27][28][29][30], three on Adxbladder [31][32][33], two on Uromonitor [34,35], and two on Cxbladder Monitor [36,37].…”