MP63-02: Prospective Multi-institutional Validation of a 3-Gene mRNA Biomarker Panel for Detection and Surveillance of Non-Muscle Invasive Bladder Cancer
Introduction: Risk stratification for patients with non-muscle invasive bladder cancer (NMIBC) is essential for treatment planning. Urinary biomarkers based on mRNA are a promising non-invasive modality for potential augmentation of current detection and surveillance methods. Previously we reported a 3-gene mRNA panel strongly associated with bladder cancer (BCa) showing promise as a screening and surveillance assay. Here we validate the performance of this assay prospectively in a multi-institution cohort to further demonstrate its potential utility in the management of NMIBC. Methods: Urine samples were collected from patients undergoing BCa screening and surveillance between 2016 and 2022 at Stanford University and the Veterans Affairs Palo Alto Health Care System. Patients with lesions concerning for bladder cancer on cystoscopy underwent transurethral resection, with stage and grade determined by histopathologic diagnosis. BCa incidence were categorized by AUA risk stratification. Voided urine samples were collected, centrifuged, and RNA was isolated from the pellet. qPCR was performed to evaluate expression of ROBO1, CRH, and IGF2. Assay positivity was evaluated via previously published formula, and sensitivity and specificity for the detection of any BCa, as well as increased-risk disease (AUA intermediate and high-risk NMIBC), were determined. Results: 216 patients provided urine samples at time of diagnostic cystoscopy, and 233 patients provided 587 samples at surveillance cystoscopies. In the detection cohort, 88 new cancers were diagnosed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the biomarker panel for any BCa was 1, 0.43, 0.53, and 1 respectively. In the surveillance cohort 189 recurrences occurred. For detection of any recurrence, the sensitivity, specificity, NPV, and PPV of the biomarker panel were 0.97, 0.24, 0.41, and 0.96, and for increased-risk disease, were 0.98, 0.25, 0.36, and 0.96 respectively. Using this assay, 59 cystoscopies (25%) could have been avoided in the detection group without missing a single incidence of BCa, and 96 cystoscopies (17%) could have been avoided in the surveillance group while missing only 4 increased-risk BCas. Conclusions: The 3-gene urinary mRNA biomarker panel shows high sensitivity for detection of NMIBC in an extended patient cohort. With further validation in prospective trials, this panel may facilitate biomarker-informed BCa screening and surveillance. SOURCE OF Funding: Department of Veterans Affairs BLR&D Merit Review I01 BX004962
