Evaluation of Cxbladder Compared to the Conventional Workup of Haematuria to Exclude a Diagnosis of Urothelial Carcinoma

Background/Objectives: Haematuria is a common presenting symptom of Urothelial Carcinoma (UC). Traditionally, the “triple workup”—comprising flexible cystoscopy, voided urine cytology and upper tract imaging is used as the standard diagnostic approach for evaluating these patients. However, these investigations can be invasive, time-consuming, and costly. Cxbladder, a urine based genomic biomarker, utilises a non-invasive, singular urine sample to calculate probability of UC based on a patient’s risk factors and gene expression. The aim of Cxbladder is to establish patients with a high probability of no UC being present, which suggests that the traditional investigations are not required. This study evaluates the performance of Cxbladder Triage compared to the standard triple workup in patients presenting with haematuria, excluding a diagnosis of UC. Methods: A prospective, observational study was conducted at a single Australian tertiary hospital. A total of 258 patients, who presented with haematuria from 2020 to 2023, underwent both a Cxbladder Triage test and standard triple workup, comprising three urine cytology samples, imaging and a flexible cystoscopy. Some patients required either a bladder biopsy or tumour resection to further diagnose and treat a suspected UC. Diagnostic accuracy was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the proportion of missed tumours. Results: Overall, 5.4% of patients, presenting with haematuria were diagnosed with UC (n = 14). Cxbladder Triage demonstrated a sensitivity of 92.9% (95% confidence interval [CI]: 66.0–99.8) and an NPV of 92.9% (95% CI: 66.0–99.8). This was higher than cytology alone, which recorded a sensitivity of 42.9% (CI 9.9–81.6%) and NPV of 78.9% (95% CI: 54.4–94.0) for the detection of UC. When cytology and imaging were combined to investigate UC, the sensitivity and NPV recorded were 75.0% (95% CI: 42.8–94.5) and 80.0% (95% CI: 51.9–95.8), respectively. The proportion of UC cases missed by Cxbladder Triage was 6.7% (n = 1). Conclusions: In our cohort of patients presenting with haematuria, Cxbladder Triage offers a non-invasive alternative to the traditional workup for the detection of UC, with both a high sensitivity and NPV. Cxbladder Triage offers an alternative diagnostic workup for low-risk patients, which has the potential to reduce unnecessary invasive tests, procedures, and cost to the healthcare system.