Bladder cancer risk stratification using a urinary mRNA biomarker panel – A path towards cystoscopy triaging

Abstract

ObjectivesThe risk of bladder cancer (BCa) diagnosis and recurrence necessitates cystoscopy. Improved risk stratification may inform personalized triage and surveillance strategies. We aim to develop a urinary mRNA biomarker panel for risk stratification in patients undergoing BCa screening and surveillance. Methods and MaterialsUrine samples were collected from patients undergoing cystoscopy for BCa screening or surveillance. In patients who underwent transurethral resection of bladder tumor, urine samples were categorized based on tumor histopathology, size, and focality. Subjects with intermediate and high-risk BCa based on American Urological Association (AUA) guideline for non-muscle invasive bladder cancer were classified as “increased-risk”; those with no cancer and AUA low-risk BCa were classified as “low-risk”. Urine was evaluated for ROBO1, WNT5A, CDC42BPB, ABL1, CRH, IGF2, ANXA10, and UPK1B expression. A diagnostic model to detect “increased-risk” BCa was created using forward logistic regression analysis of cycle threshold values. Model validation was performed with ten-fold cross-validation. Sensitivity and specificity for detection of “increased-risk” BCa was determined and net benefit analysis performed. ResultsUrine samples (n = 257) were collected from 177 patients (95 screening, 76 surveillance, 6 both). There were 65 diagnoses of BCa (12 low, 22 intermediate, 31 high risk). ROBO1, CRH, and IGF2 expression correlated with “increased-risk” disease yielding sensitivity of 92.5% (95% CI, 84.9%–98.1%) and specificity of 73.5% (95% CI, 67.7–79.9%). The overall calculated standardized net benefit of the model was 0.81 (95%CI, 0.71–0.90). ConclusionsA 3-marker urinary mRNA panel allows for non-invasive identification of “increased-risk” BCa and with further validation may prove to be a tool to reduce the need for cystoscopies in low-risk patients.