Comparison of the performances of the ADXBLADDER test and urinary cytology in the follow-up of non-muscle-invasive bladder cancer: a blinded prospective multicentric study

Abstract

Objective: To compare directly the performance of the ADXBLADDER test with that of cytology in the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences.

Background: ADXBLADDER is a urine test based on the detection of MCM5, a DNA licensing factor expressed in all cells capable of dividing. Expression is usually restricted to the basal stem cell compartment; however, in malignancy, MCM5-expressing cells can be found throughout the epithelium. Detection of MCM5 in urine sediment can be indicative of the presence of a bladder tumour.

Patients and methods: A multicentre prospective, blinded study was carried out from August 2017 and July 2019 at 21 European Union centres, 14 of which collected matching cytology data. Urine was collected from patients prior to cystoscopy. Urine cytology and ADXBLADDER were performed and compared to the diagnosis obtained by cystoscopy. The performance of cytology and ADXBLADDER were then compared.

Results: The overall performance of ADXBLADDER demonstrated a sensitivity of 51.9%, a specificity of 66.4%, and a negative predictive value (NPV) of 92%. The sensitivity of ADXBLADDER for low- and high-grade recurrences was 44.1% and 58.8%, respectively. By contrast, cytology sensitivity was 16.7%, specificity was 98% and NPV was 90.7%. Cytology sensitivity for both low- and high-grade disease was 17.6%.

Conclusions: ADXBLADDER detection of both low- and high-grade NMIBC recurrence is superior to that of cytology, with ADXBLADDER able to exclude the presence of high-grade recurrence in 97.8% of cases compared to 97.1% with cytology. These results show that ADXBLADDER has promise as a more reliable alternative to urine cytology in the follow-up of NMIBC.

Keywords: #BladderCancer; #blcsm; #uroonc; #utuc; biomarker; bladder cancer; cytology MCM5; follow-up; non-muscle-invasive bladder cancer; surveillance.

Conflict of interest statement

This was a commercially sponsored study by Arquer Diagnostics Ltd. M. Roupret, P. Gontero, S. R. C. McCracken, T. Dudderidge, M. Colombel, F. Longo, E. Montanari and J. Palou are paid consultants to Arquer Diagnostics. J. A. Witjes has received fees for lecture honorarium for Nucleix. None has any shareholding in Arquer Diagnostics or any related company. J. Stockley and A. Kennedy are employees of Arquer Diagnostics holding share options in the company. The funder of the study assisted the authors in study design, data collection, data analysis, data interpretation, writing of the report, and the decision to submit the paper for publication. P. Gontero, M. Roupret, E. Montanari, F. Longo, T. Dudderidge, J. Palou and S. R. C. McCracken, had access to the raw data. The corresponding author had full access to all the data and had the final responsibility to submit for publication.

© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Figures

Fig. 1

Standards for Reporting of Diagnostic Accuracy (STARD) patient recruitment and enrolment outline. MIBC, carcinoma invading bladder muscle.

Fig. 2

Comparison of sensitivity (95% CI) of ADXBLADDER vs cytology by recurrent tumour classification: in all tumours (*P < 0.001), low‐grade tumours (**P = 0.02), high‐grade tumours (***P = 0.04) and Excl pTa low‐grade (****P = 0.006).