Performance of the URO17® Test in Detecting Bladder Cancer - Expert Commentary

Cytoscopy is the gold standard for bladder cancer diagnosis. The common non-invasive alternative is urine cytology, which has high specificity but a low sensitivity rate of approximately 34% and a high degree of inter-rater variability. Various non-invasive tests have been commercialized but they exhibit variable rates of sensitivity and specificity and have not been integrated into clinical practice. The URO17® test relies on keratin 17 (K17), an intermediate filament protein that binds important oncogenic proteins. K17 staining of urine cytology samples has been shown to have high levels of sensitivity and specificity in detecting urothelial carcinoma.

Porten et al. aimed to further evaluate the performance of URO17®. The test was used on 152 participants undergoing procedures for urologic malignancies, of which 76 were cases and 76 were controls. The median age of cases was 70 and the median age of controls was 65. The majority of cases underwent endoscopic bladder procedures (90%) and 54% received intravesical therapy before the study. Over a third of patients exhibited urothelial carcinoma recurrence. Overall, the URO17® test was associated with a sensitivity of 90% and a specificity of 88% (n = 167). In patients with suspected urothelial carcinoma (n = 91), the sensitivity was 90% and specificity was 53%. Positive predictive value (PPV) was consistent across subgroups, but negative predictive value (NPV) varied based on the subgroup (67 – 100%). No controls had a positive URO17® result. The test outperformed urine cytology in detecting low-grade or high-grade disease. However, there were 21 false positive and 6 false negative results.

The URO17® test outperformed many existing non-invasive tests but had a low specificity rate. This is likely due to factors including inflammation or prior BCG therapy. The relatively high PPV and NPV values suggest URO17® could be useful for ruling out active urothelial cancer. Prospective validation studies in larger cohorts, particularly to distinguish between confounding factors such as previous treatment are warranted. As urine new cell-free DNA technologies mature, it will be important to compare cell-based and cell-free based methods for urothelial cancer detection.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Porten SP, Wang EY, Vohra P, Carroll PR, Jahanfard S, Kim NW. Evaluation of URO17® to improve non-invasive detection of bladder cancer. Urol Oncol. 2024;42(6):176.e21-176.e28. doi:10.1016/j.urolonc.2024.02.012

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