Refining risk stratification after indeterminate urinary cytology: Evidence from Bladder EpiCheck

Abstract

BACKGROUND: This study aimed to evaluate Bladder EpiCheck (BE) performance in detecting urothelial carcinoma (UC) and HG (high-grade) events in patients with indeterminate cytology and negative cystoscopy. METHODS: This prospective study included 63 patients who presented with indeterminate urinary cytology and negative cystoscopy between October 2022 and April 2024. A repeated urine sample was obtained and analyzed via both urinary cytology and BE test. Patients were followed for 1 year. The diagnostic performance of each test was assessed. Logistic regression models were developed to estimate the risk of UC and HG events on the basis of repeated cytology and BE results. RESULTS: Thirty-two patients (51%) experienced a UC event, of which 25 (78%) were HG events. Sensitivity (SN) for detecting UC events was significantly higher (80% vs. 17%; p < .001) for BE compared to repeated urinary cytology, whereas repeated cytology demonstrated higher specificity (SP) (59% vs. 96%; p = .02). Similar SN differences were observed for HG disease (80% vs. 25%; p < .001). However, when suspicious for high-grade urothelial carcinoma was considered a positive cytology result, no statistically significant differences were observed between BE and repeated cytology in either SN or SP. A prognostic model combining repeated cytology and BE outperformed models using baseline cytology combined with either test alone in predicting UC and HG events. CONCLUSIONS: In patients with indeterminate urinary cytology and negative cystoscopy, BE provided complementary diagnostic information for the detection of UC events and HG disease. The combination of BE and repeated urinary cytology provided the most accurate risk assessment.