Xpert Bladder Cancer Monitor for the Early Detection of Non-Muscle Invasive Bladder Cancer Recurrences: Could Cystoscopy Be Substituted?

SIMPLE SUMMARY: Non-muscle invasive bladder cancer (NMIBC) accounts for three quarters of newly detected bladder tumors. NMIBC can be treated conservatively with a bladder transurethral resection (bTUR), although recurrences are common despite adjuvant treatments. High-risk recurrent NMIBC can progress to muscle invasive bladder cancer (MIBC) and decrease survival. Therefore, close invasive surveillance, based on cystoscopy and washing cytology, is currently recommended, especially in high-risk recurrent tumors. Urine biomarkers have been investigated unsuccessfully to avoid or postpone the invasive surveillance of NMIBC. Xpert Bladder Cancer Monitor(®) (XBM) is a new genetic urine biomarker that assesses the expression of five miRNA profiles. In the present study, XBM was not sensitive enough to detect all high-risk recurrences and avoid cystoscopy and washing cytology. However, false positive XBM results can predict early high-risk recurrences. ABSTRACT: XBM was prospectively assessed in spontaneous urine collected just before flexible cystoscopy and washing cytology carried out within the first 2 years follow-up of 337 patients with NMIBC. Recurrences were pathologically confirmed in 49 patients (14.5%), 22 of them being high-risk (6.5%). The XBM sensitivity for detecting any type of recurrence was 69.4% and 63.6% in the cases of high-risk NMIBC. Negative predictive value (NPV) for XBM was 93% for all recurrences and 96.2% for high-risk recurrences. XBM could have avoided 213 invasive controls but missed the detection of 15 recurrences (30.6%)–8 of them of high-risk (36.4%). XBM false positive elevations were detected in 90 patients (26.7%), whereas 10 patients with the invasive method had a false positive result (3%), p <0.001. However, early detection of recurrences during the first year’s follow-up after an XBM false positive result was observed in 18 patients (20%). On the other hand, 19 recurrences were detected during this period among the rest of the patients (7.7%)—p = 0.003, and odds ratio (OR) 3.0 (95% CI 1.5–6.0). Regarding one-year follow-up recurrences, 10% were high-risk recurrences in the XBM false positive group and 3.2% in the rest of the patients—p = 0.021, and OR 3.3 (95% CI 1.2–8.9). Additionally, 11.3% of the patients without false positive results developed a recurrence, p = 0.897, for any recurrence, being 10% and 5.2%, respectively, and high-risk and low-risk recurrences, p = 0.506. After searching for the best XBM cutoff for detecting the 38 high-risk initial recurrences and the early high-risk recurrences after a one-year follow-up, a linear discriminant analysis (LDA) of 0.13 could have avoided 11.3% of cystoscopies and bladder wash cytologies, as this cutoff missed only 1 high-risk recurrence (2.6%). More extensive and well-designed studies will confirm if XBM can improve the surveillance of NMIBC.