mRNA-Based Urine Test Performance in High and Very-High Risk Non–Muscle-Invasive Bladder Cancer Patients Undergoing Contextual Endoscopic Follow-up (VERNAL: Vesical Tumor Early Monitoring: mRNA-Based Follow-up)

Abstract

Introduction and Objectives

Non–muscle-invasive bladder cancer (NMIBC) patients need a strict follow-up with cystoscopy (UCS) and voided urinary cytology (vUC) due to high rate of recurrence and progression. To reduce invasiveness and costs, a new diagnostic biomarker, namely Xpert Monitor BC^Ⓡ—detecting 5 mRNAs in voided urine—, has been proposed. We test Xpert Monitor BC^Ⓡ ability to detect tumor recurrence at an early point during follow-up of high risk (HR) or very high risk (VHR) NMIBC patients, aiming at evaluating reliability of this test as a single procedure.

Materials and Methods

Between September 2022 and July 2023 included, 80 HR or VHR NMIBC patients were prospectively enrolled. Both naïve and previously treated patients (including Bacillus Calmette-Guérin—BCG—and/or systemic immunotherapy) were admitted. Patients with known upper urinary tract urothelial carcinoma (UTUC) were excluded. Xpert Monitor BC^Ⓡ test was carried out on precystoscopy voided urine samples. In case of suspicious urethra-cystoscopy (UCS), a transurethral resection (TURB) or a biopsy was indicated. vUC was usually prescribed to be performed prior to UCS. Negative predictive value (NVP), positive predictive value (PPV), sensitivity (SE) and specificity (SP) of Xpert Monitor BC^Ⓡ and vUC, were assessed and compared with UCS and secondarily with histology at TURB/bladder biopsy.

Patients who proceeded with follow-up underwent a second evaluation with Xpert Monitor BC^Ⓡ test.

Results

Seventy-six patients were evaluable. Median age was 70 years (interquartile range [IQR] 65-78) and 62 (81.6%) patients were male. VHR patients were 14 (18.4%), 47 (61.8%) had a history of carcinoma in situ (CIS) and 37 (49.3%) had multifocal disease while 51 patients (67.1%) had recurrent bladder cancer (BC).

BC recurred in 15 patients (19.7%): in 3 of them as a muscle-invasive bladder cancer (MIBC). Xpert Monitor BC^Ⓡ showed a NPV, PPV, SE, SP of 95.3% (41/43), 57.6% (19/33), 90.5% (19/21) and 74.5% (41/55) respectively. When available, vUC displayed a NPV of 78.9% (30/38), a PPV of 75% (3/4), a SE of 27.3% (3/11) and a SP of 96.7% (30/31). Twenty patients underwent a subsequent Xpert Monitor BC^Ⓡ test and UCS during their follow-up, and 3 had a bladder cancer recurrence. Of note Xpert Monitor BC^Ⓡ was positive in all those 3 patients who previously tested positive despite a negative UC.

Conclusions

High NPV and SE of Xpert Monitor BC^Ⓡ are confirmed in our HR and VHR NMIBC series. Apparent false positive tests may be regarded as suspicious for persistent/recurrent disease. Implementation of Xpert Monitor BC^Ⓡ aiming at improving cancer detection is supported by these findings, and a single test based follow-up may be explored.