MCM5 urine expression (ADXBLADDER) is a reliable biomarker of high-risk non- muscle-invasive bladder cancer recurrence: A prospective matched case-control study

Abstract

BACKGROUND: Mini Chromosome Maintenance 5 (MCM5) is considered as a urinary biomarker of bladder cancer. ADXBLADDER is a commercially available test to detect MCM5 antibodies. OBJECTIVE: External validation of ADXBLADDER test as a urinary biomarker of histopathologically confirmed non-muscle invasive bladder cancer (NMIBC) recurrence. METHODS: The study enrolled 119 consecutive patients with a history of NMIBC and 37 healthy volunteers matched as controls. Single, full-void urine samples were collected from patients before cystoscopy ± TUR. To measure MCM5 expression, Arquer Diagnostics ADXBLADDER test was used. The study protocol was registered within the clinical trials database (NCT03796299). RESULTS: Among patients with NMIBC history, recurrence was diagnosed in 83 patients (69.7%). ADXBLADDER demonstrated sensitivity of 73.5% (95% confidence interval (CI) 62.7%–82.6%), specificity of 33.3% (95% CI 18.6% to 51%), overall negative predictive value (NPV) of 35.3% (95% CI 23.3% to 49.5%) and overall positive predictive value of 71.8% (95% CI 66.1% to 76.8%) for detecting recurrence. In a control group, false positive ADXBLADDER results were noticed in 18 patients (48.6%). The sensitivity and NPV were the highest in invasive tumors (100% and 100%, respectively) and in high-grade recurrences (81.8% and 94.1%, respectively). CONCLUSIONS: ADXBLADDER has a moderate sensitivity and poor specificity in detecting NMIBC recurrence. However, it properly diagnoses patients with T1+ stage recurrence or high-grade tumors.

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].…”

“…The prevalence of disease for each UBT is reported in Table 1. The pooled recurrence rate was calculated at 18%, with significant heterogeneity across studies with rates ranging from 6% [36] up to 70% [32].…”

“…Three studies provided data on the diagnostic values of the ADXBLADDER test for the diagnosis of recurrence during NMIBC follow-up [31][32][33]. The forest plots revealed that the pooled Se, Sp, PPV, and NPV were 0.57 (95% CI 0.39-0.73), 0.62 (95% CI 0.51-0.72), 0.29 (95% CI 0.08-0.67), and 0.82 (95% CI 0.53-0.95), respectively (Fig.…”

The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers—What Should a Urologist Really Know?

“…However, in some studies, pTa low-grade cases were regarded as negative for BCa, increasing, therefore, NPV. Nevertheless, according to these results, a negative test could indicate the absence of the recurrence [ 65 , 66 , 67 , 68 , 69 , 70 ].…”

Bioinformatic Analysis of the Expression and Clinical Significance of the DNA Replication Regulator MCM Complex in Bladder Cancer

“… 33 MCM5 urine expression had moderate sensitivity to detect non-muscle invasive relapse and could correctly diagnose T1 stage relapse or high-grade tumor. 34 Immunocytochemistry with MCM5 antibodies from urine can improve the ability of urinary cytology to detect urothelial carcinoma of the bladder. 35 Another study also indicated that MCM5 was a novel biomarker for the diagnosis of ovarian cancer.…”