A Review of Urine Ancillary Tests in the Era of the Paris System

Aside from its diagnostic importance, urinary tract endoscopy is an uncomfortable, expensive, and time-consuming procedure. Patients with a history of urothelial carcinoma remain at an increased risk for recurrence and the development of de novo disease; most have had exposure to carcinogenic risk factors for decades prior to their first diagnosis that have bathed the entire urothelial tract. Consequently, monitoring these patients over their lifetime has made urothelial carcinoma one of the most expensive cancers for the US healthcare system. This expense has provided a financial incentive for academic and commercial groups to develop a test with a sufficient negative predictive value to reduce the frequency of surveillance procedures. Slide-based tests require a separate slide prepared from a split urine sample or from an additional urinary tract specimen. This process can place an additional burden on the laboratory due to changes in the workflow, especially if the split specimens need to be stored until a cytologic diagnosis is rendered (i.e., when used as a reflex test). Importantly, slide-based tests allow for the result to be directly correlated with cytomorphologic findings; however, these tests require the cells of interest to be present. Thus, slide-based tests suffer from the same sensitivity issues as urinary tract cytology. In contrast, slide-free tests do not require an additional slide to be prepared, and laboratory testing may be centralized to a core facility or performed on-site. Some tests detect the expression of altered or abnormally expressed subcellular material (proteins, DNA, etc.) in urothelial neoplasms, which are found in tumor cells and/or in the urine specimen when the proteins are either excreted or leaked from degenerating tumor cells. Slide-free tests may also be developed into point-of-care tests, meaning that the result may be available to the urologist but not to the cytopathologist. Since these proteins are often disassociated from the tumor cells that produce them, such tests may have a positive result even if tumor cells are absent in the tested specimen. Here we review critical concepts as well as several ancillary tests that have been developed for urinary tract specimens.