Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma

Abstract

The Cxbladder Monitor test significantly outperforms current Food and Drug Administration-approved urine-based monitoring tests, as well as cytology, in a large representative population undergoing surveillance for recurrent UC. This supports using Cxbladder Monitor as a confirmatory negative adjunct to cystoscopy or to justify postponing cystoscopic investigations in patients with a low risk of recurrence.

An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer

“…According to a phased approach, NMP22 tests reached phase III (independent confirmation studies). Recently, four marker-comparison studies have been published, reporting low sensitivity rates of the qualitative test in detecting Rec (11–58%) [7, 18–20]. In contrast, the quantitative NMP22BC test is measured on a continuous scale and then transformed into a dichotomous variable by choosing a cut-off threshold (estimated at 10 ng/mL).…”

“…From a biologic point of view, the use of a cut-off does not make much sense in the context of the continuity that the appearance of this marker represents, and therefore, generally leads to lower overall accuracy. Indeed, NMP22 BladderChek had a very poor sensitivity level for detecting Rec (26%), which only slightly outperformed that obtained with NMP22BC in the same population [7]. However, in a decision curve analysis, NMP22 was associated with oncological outcomes; it has been suggested that this test could be useful in decision-making between an immediate and delayed cystoscopy, depending on a clinician’s threshold to perform a surveillance cystoscopy [21].…”

“…Unfortunately, the most used urinary test, cytology, suffers from insufficient reproducibility and robustness to suffice for utility in various clinical scenarios such as surveillance of the most common type of BCa (low-grade NMIBC) [5, 6]. Recent multicenter studies have also shown a lower sensitivity of cytology for high-grade cancer compared to historical data [7, 8]. Urinary biomarkers in the surveillance setting have three aims: to reduce the frequency of invasive testing while still detecting early disease recurrence (Rec), to exclude the presence of recurrent disease and to detect progression (Prog) in non-muscle invasive bladder cancer (NMIBC) patients and predicting response to therapies [9].…”

Microdevices for Non-Invasive Detection of Bladder Cancer

“…Urine cytology is the standard non-invasive urine test that relies on visual inspection of abnormal cells in patient's urine under a microscope [41,42]. However, it is limited by its low sensitivity, especially in the detection of low-stage, low-grade bladder cancer [40,[63][64][65]. For such bladder tumors in early stages of development, the sensitivity of cytology is approximately 20% [66,67].…”

“…Furthermore, histological examinations have limited ability for prognostication as they do not reflect biological behaviour of the tumor, merely physical appearance [44]. High levels of inter-observer, intra-observer, and institutional variability also reduce the reliability of urine cytology results [40]. In addition, cytology requires highly trained personnel for sample evaluation, who may not be available in all areas [68].…”