Noninvasive multianalyte diagnostic assay for monitoring bladder cancer recurrence.

BACKGROUND: The purpose of this study was to establish the clinical performance of a urine-based assay, called a multianalyte diagnostic readout, in monitoring for bladder cancer recurrence. METHODS: This was a prospective, multicenter, single assessment observational study. The multianalyte diagnostic readout uses a combination of one protein and three DNA biomarkers. Urine samples from 733 patients undergoing monitoring for bladder cancer recurrence were analyzed for matrix metalloproteinase-2 levels, the presence of mutant FGFR3 DNA, and hypermethylation of the NID2 and VIM genes. The probability of a patient having (positive predictive value) or not having (negative predictive value) recurrent bladder cancer was determined by FGFR3 alone or all four biomarkers combined, respectively. RESULTS: Cystoscopy/biopsy diagnosed 63 patients with bladder cancer recurrence at the time of study assessment. The four-biomarker assay identified 237 patients as having a low probability of disease recurrence, 231 of whom were determined by cystoscopy as not having recurrent cancer, resulting in a negative predictive value of 97.5% at 90.5% sensitivity. The FGFR3 assay identified 49 patients with FGFR3 mutations, 19 of whom were confirmed by biopsy as having cancer, resulting in a positive predictive value of 38.8%, with 95.5% specificity. CONCLUSION: The urine-based multianalyte diagnostic readout assay was able to delineate the patient population into those highly likely to have bladder cancer recurrence, those unlikely to have recurrent disease, and those with an average risk for bladder cancer recurrence.