Molecular Test Stratifies Patients with Bladder Cancer Symptoms

A urine-based molecular diagnostic combines clinical risk factors and gene expression biomarkers to accurately triage patients presenting with blood in their urine (hematuria) who have a low probability of urothelial cancer (UC or bladder cancer).

Hematuria can be symptomatic of UC and ruling out patients with benign causes of such bleeding during primary evaluation is challenging. Patients with hematuria must typically undergo a full urological workup to investigate the possibility of bladder cancer, with a corresponding increase in the overall clinical and financial burden of these patients on health care systems.

Urologists at Palmerston North Hospital (New Zealand) working with a commercial company collected data from 587 patients with macrohematuria. Expression of five genes in a voided urine sample (genotypic) and age, gender, frequency of macrohematuria and smoking history (phenotypic) was analyzed. To provide gene expression data, a single mid-stream urine sample was collected from participants using the Urine Sampling System. Multigene analysis of samples from all studies was carried out in accordance with the standard operating procedure, as is used for the commercially available multigenic test.

Both urine sampling system and the multigenic Cxbladder Triage test are products of Pacific Edge Ltd. (Dunedin, New Zealand). Cxbladder Triage is a novel molecular test that combines the power of the genomic biomarkers with extra phenotypic and clinical risk factors to accurately identify and remove patients with hematuria who have a low probability of bladder cancer, from needing to have a full-urological work-up. In total, samples from 587 patients were available for modelling comprising 72 UC-positive and 515 UC-negative samples. A combined genotypic-phenotypic model (G + P INDEX) was compared with genotypic (G INDEX) and phenotypic (P INDEX) models. Area under receiver operating characteristic curves (AUC) defined the performance of each INDEX.

The G + P INDEX offered a bias-corrected AUC of 0.86 compared with 0.61 and 0.83, for the P and G INDEXs respectively. When the test-negative rate was 0.4, the G + P INDEX (sensitivity = 0.95; negative predictive value (NPV) = 0.98) offered improved performance compared with the G INDEX (sensitivity = 0.86; NPV = 0.96). In all 80% of patients with microhematuria who did not have UC were correctly triaged out using the G + P INDEX, therefore not requiring a full urological work-up.

David Gregory Darling, Chief Executive Officer of Pacific Edge, said, “This study shows that Cxbladder Triage can accurately identify those patients who have a low probability of UC with a high level of sensitivity (95%) and high negative predictive value NPV (98%). The use of this test will enable physicians to evaluate those patients presenting with hematuria, and quickly and accurately remove those with a low probability of cancer, thereby reducing the number of individuals who require an expensive and invasive full urological workup. The use of Cxbladder Triage will also allow clinicians to make effective choices about the deployment of their skills and capabilities on the patients who need it most.” The study was published on March 27, 2015, in the journal BMC Urology.

Related Links:
Palmerston North Hospital 
Pacific Edge Ltd.