PURPOSE: Accurate urine assays for bladder cancer detection would benefit 
patients and health care systems. Through extensive genomic and proteomic 
profiling of urine components we previously identified a panel of 8 biomarkers 
that can facilitate the detection of bladder cancer in voided urine samples. In 
this study we confirmed this diagnostic molecular signature in a diverse 
multicenter cohort.
MATERIALS AND METHODS: We performed a case-control, phase II study in which we 
analyzed voided urine from 102 subjects with bladder cancer and 206 with varying 
urological disorders. The urinary concentration of 8 biomarkers (IL-8, MMP-9 and 
10, PAI-1, VEGF, ANG, CA9 and APOE) was assessed by enzyme-linked immunosorbent 
assay. Diagnostic performance of the panel of tested biomarkers was evaluated 
using ROCs and descriptive statistical values, eg sensitivity and specificity.
RESULTS: Seven of the 8 urine biomarkers were increased in subjects with bladder 
cancer relative to those without bladder cancer. The 7 biomarkers were assessed 
in a new model, which had an AUROC of 0.88 (95% CI 0.84-0.93), and 74% 
sensitivity and 90% specificity. In contrast, the sensitivity of voided urine 
cytology and the UroVysion® cytogenetic test in this cohort was 39% and 54%, 
respectively. Study limitations include analysis performed on banked urine 
samples and the lack of voided urine cytology and cytogenetic test data on 
controls.
CONCLUSIONS: The study provides further evidence that the reported panel of 
diagnostic biomarkers can reliably achieve the noninvasive detection of bladder 
cancer with higher sensitivity than currently available urine based assays.