Liquid biopsies are increasingly used for the diagnosis and follow-up of cancer patients. Urine is a body fluid that can be used to detect cancers and others diseases. It is noninvasive and easy to collect. To detect Bladder Cancer (BC), cytology is the first assay used. It is an effective way to detect high grade BC but has a high rate of equivocal results, especially for low grade BC. Furthermore, cystoscopy is used to confirm cytology results and to determine cancer status. Cystoscopy is also effective but highly invasive, and not well accepted by patients, especially for BC follow-up. In this review we survey the numerous assays recently developed in order to diagnose BC at an early stage, and to facilitate the follow-up of patients. We discuss their effectiveness, ease of use, and applications. Finally, we discuss assays that, in the future, could improve the diagnosis and management of BC patients.

Urine cytology is non-invasive, easy to collect, with medium sensitivity and a high specificity. It is an effective way to detect high-grade bladder cancer (BC), but it is less effective on low-grade BC because the rate of equivocal results is much higher. Recently, the fluorescent properties of plasma membranes of urothelial tumor cells (UTC) found in urine cytology have been shown to be useful in improving the early detection of BC. This phenomenon is called peri-membrane fluorescence (PMF). Based on previous studies that have identified the PMF on UTCs, the main objective was to characterize this phenomenon. For this study, a software was specially created to quantify the PMF of all tested cells and different treatments performed. PMF was not found to be a morphological and discriminating feature of UTCs, all cells in shape and not from urine show PMF. We were able to highlight the crucial role of plasma membrane integrity in the maintenance of PMF. Finally, it was found that the induction of a strong cellular stress induced a decrease in PMF, mimicking what was observed in non-tumor cells collected from urine. These results suggest that PMF is found in cells able to resist this stress, such as tumor cells.