Predictive value of MCM5 (ADXBLADDER) analysis in urine of men evaluated for the initial diagnosis of bladder cancer: A comparative prospective study

Abstract

Background: To compare predictive value of MCM5 to urinary cytology (UC) for the primary diagnosis of bladder cancer (BCa). Methods: We prospectively enrolled 91 patients who presented macroscopic hematuria or persistent lower urinary tract symptoms at our institution. Single voided midstream urine specimens were collected for UC and MCM5 (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, United Kingdom) assessment. Cystoscopy was used as confirmatory test, and positive cases underwent transurethral resection of bladder tumor with histopathological evaluation. Results: Forty cases (43.9%) showed a positive cystoscopy for BCa. Histology was obtained in 37 cases: 16 (43.2%) high-grade (HG) and 21 (56.8%) low-grade (LG) transitional cell carcinoma (TCC). UC had a sensitivity of 62.5%, specificity of 86.3%, PPV of 78.1% and NPV of 74.6%. Sensitivity, specificity, PPV and NPV of MCM5 were 60.0%, 88.2%, 80.0% and 73.8%, respectively. According to tumor grade, MCM5 and UC showed a sensitivity of 47.6% and 52.4% in LG, and 87.5% and 75.0%, respectively, in HG TCC. False-positive rates were 11.8% and 13.7% of negative cases for BCa with MCM5 and UC test, whereas false-negative results were found in 40.0% and 37.5% of BCa cases, respectively. The combination of the two tests showed a sensitivity of 71.4% in LG, and 93.8% in HG TCC. Conclusion: In the present analysis, MCM5 showed lower sensitivity than UC in predicting BCa primary diagnosis. According to tumor grade, MCM5 showed a higher sensitivity in the detection of HG BCa compared to UC, although values were not significantly different.

Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis

“…Seven studies reported on the diagnostic values of the novel UBTs for the detection of NMIBC during initial diagnosis [34,[39][40][41][42][43][44]. Table 2 summarizes the characteristics of included studies and their main outcomes.…”

“…In terms of Sp, the Xpert bladder cancer test had the highest estimates of 90% in patients with hematuria [40]; in the overall population, it ranged from 77% [40] to 84% [39]. The ADXBLADDER test demonstrated Se up to 87% in patients diagnosed with HG NMIBC, compared with 48-55% in patients diagnosed with LG tumors [41,42]. Similarly, Cxbladder (mix of Triage and Detect) reached the highest Se value of 97% in patients with HG tumors [43,44].…”

Xpert Bladder Cancer Monitor May Avoid Cystoscopies in Patients Under “Active Surveillance” for Recurrent Bladder Cancer (BIAS Project): Longitudinal Cohort Study

“…In our study, by replacing the UC with Xpert BC Monitor performed over time, we could have avoided up to 73%, 86.2%, or even up to all unnecessary cystoscopies, depending on whether the patient had two, three, or four consecutive negative tests. The panorama of emerging urinary biomarkers in the diagnosis and surveillance of NMIBC is wide, but none are currently included in daily clinical practice probably due to the availability, the cost that limits their use (44)(45)(46)(47).…”

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

“…Nevertheless, XPERT test with two negative tests avoids nearly 75% of unnecessary cystoscopies [ 229 , 230 , 231 , 232 , 233 , 234 ]. ADXBLADDER™ test measures the expression of MCM5 transcript [ 235 , 236 , 237 ]. In a large blinded prospective study ADXBLADDER™ test had an overall sensitivity of 44% but was able to exclude the presence of the most aggressive tumors with a negative predictive value of 99%.…”

“…In a large blinded prospective study ADXBLADDER™ test had an overall sensitivity of 44% but was able to exclude the presence of the most aggressive tumors with a negative predictive value of 99%. In another study, the test’s sensitivity was lower than urine cytology [ 235 , 237 ].…”