A Novel Urine-Based Assay for Bladder Cancer Diagnosis: Multi-Institutional Validation Study

Abstract Background CellDetect is a unique histochemical stain enabling color and morphological discrimination between malignant and benign cells based on differences in metabolic signature. Objective The objective of the present study was to validate the performance of this assay in a controlled, blinded, multicenter study. Design, setting, and participants The study, conducted in nine hospitals, included patients with documented history of bladder cancer, monitored for urothelial carcinoma (UCC) or scheduled for bladder cancer surgery. Outcome measurements and statistical analysis Cystoscopy and/or biopsy were used as a reference standard to determine sensitivity and specificity. Smears were stained by CellDetect and interpreted by two cytologists blinded to the patient's final diagnosis. The findings were compared with those of standard urine cytology and BTA stat. Results and limitations Two hundred and seventeen voided urine specimens were included. Ninety-six (44%) were positive by histology and 121 (56%) were negative by either cystoscopy or histology. The overall sensitivity of CellDetect was 84%. Notably, the sensitivity for detecting low-grade nonmuscle-invasive bladder cancer tumors was greater than this of BTA stat (78% vs 54%) and more than two-fold higher compared with standard cytology (33%, p ≤ 0.05). The specificity was 84% in patients undergoing routine surveillance by cystoscopy. At a median follow-up of 9 mo, 21% of the patients with positive CellDetect and negative reference standard developed UCC, which was significantly higher compared with the 5% of the true negative cases. Limitations include the lack of instrumental urine samples and the lack of patients with nongenitourinary cancers in the study population. Conclusions This study validates the performance of CellDetect as a urine-based assay to identify UCC in patients with history of bladder cancer. The high sensitivity was maintained across all cancer grades and stages without compromising the assay specificity. Further studies are required to test whether this novel stain can be incorporated in routine bladder cancer surveillance as a noninvasive alternative to cystoscopy. Patient summary Surveillance of bladder cancer requires frequent invasive procedures. In the present study, we validate the ability of a novel biomarker to accurately identify early-stage tumors in urine specimens for the noninvasive monitoring of patients with history of bladder cancer.