Clinical Validation of a Multiplex Urine Biomarker Assay for Surveillance of Recurrent Bladder Cancer
Yair Lotan, Michael Luu, Menghan Liu, Sergei Tikhonekov, Takashi Kobayashi, Michael Ahdoot, Hyung Lae. Kim, Sima Porten, Garry Peers, Yuki Kita, Timothy Daskivich, Kaoru Murakami, Toru Sakatani, Ian Pagano, Yingye Zheng, Zhen Zhang, Hideki Furuya, Charles J. RosserAbstract
Background: More than 50% of patients with non-muscle invasive bladder cancer (NMIBC) experience recurrence, requiring lifelong surveillance with repeated cystoscopy. Given the invasive nature and cost of cystoscopy, accurate non-invasive tools are needed to support risk-adapted monitoring. We evaluated the ability of Oncuria-Monitor to detect recurrent bladder cancer (BC) during surveillance. Methods: Between February 2017 and August 2020, six medical centers in the United States and Japan prospectively enrolled 300 patients with a history of BC, generating 1,248 serial urine samples. Participants were divided into training and validation cohorts. At each surveillance visit over two years, urine samples were analyzed in a blinded manner using Oncuria-Monitor and BladderChek™, alongside urine cytology. Test performance was compared with cystoscopy and histopathology-confirmed recurrence. Results: Recurrent BC was identified in 31% (93/300) of participants, with 143 total recurrences during follow-up, including 90 tumors in the validation cohort. In the validation cohort, Oncuria-Monitor achieved a sensitivity of 85.6% (95% CI: 78.1–92.2%) and negative predictive value (NPV) of 93.0% (95% CI: 89.2–96.4%). In comparison, BladderChek™ demonstrated a sensitivity of 20.0% and NPV of 88.0%, while urine cytology showed a sensitivity of 36.9% and NPV of 91.6%. The number needed to evaluate to detect one recurrence was 3 for both cystoscopy and Oncuria-Monitor, compared with 15 for BladderChek™ and 8 for cytology. Conclusions: In this prospective study, Oncuria-Monitor demonstrated clinically actionable performance, enabling a rule-out strategy that could safely reduce cystoscopy in approximately 25% of surveillance visits. These findings support a paradigm shift toward biomarker-guided, risk-adapted surveillance in BC.