# Confocal Laser Endomicroscopy for Bladder Cancer Detection: Where Do We Stand?
## 4 Discussion  
Since the last two decades, the impact of new endoscopic technologies has markedly changed the diagnostic and management of BCa. For example, the recent advent of digital optics has outclassed the fiber-optic system for the enhanced quality of image definition, with relevant impact on BCa detection rate. As outlined by several articles [4; 5], the residual tumor rate after the first TURBT is not negligeable. To amend that, according to current guidelines [22], it is always advised to perform a second intervention (re-TURBT), not only when the first resection results are incomplete or in the absence of muscle layer in the specimen but also in all pT1 and high-grade cases. This procedure, even if mandatory, adds morbidity to the patient and potentially increases surgical waiting lists. Moreover, several articles show the actual limits of \"white-light\" (WL) cystoscopy, which can miss a consistent number of flat lesions--estimated around 58-68% [23; 24]. To overcome those limitations, recent technological advances have been purposed and validated. The most adopted are actually the \"macroscopic\" ones, which enhance tissue vision through better visualization of tissue vascularization or by gaining better contrast between different aspects of the urothel (i.e., the Storz professional image enhancement system (SPIES) or NBI) or to allow the detection of an area with incremented cellular metabolism (i.e., PDD, also known as \"blue-light\" cystoscopy) after the injection or instillation of photosensitizing agents (mainly hexylaminolevulinate) that bind to hyper-metabolic areas; those agents are sensible to a particular light spectrum (i.e., blue light) that emphasizes those areas during cystoscopy. However, all those techniques still have limitations as they cannot clearly discriminate between neoplastic and inflammatory areas. Therefore, rising attention is now given to \"microscopic\" techniques, which allow a real-time detection of tissue components and cellular aspects [25]. Although histology is the cornerstone for cancer diagnosis, this information is not available in real time during surgical intervention. Therefore, new imaging technologies that allow a direct characterization of cell architecture appear to overcome the limits of WLC and this is strongly demanded to reduce the risk of incomplete tumor resection or understaging [21; 22]. The first purposed one is optical coherence tomography (OCT), which provides real-time cross-sectional images of tissues by means of infrared-spectrum microwaves, producing images of 2 mm in depth and 10-20 um spatial resolution [25]. With OCT it is possible to discriminate between healthy and pathological urothel and to postulate on the invasiveness of a bladder lesion. However, this technique provides no information about tumor grade [26]. Differently from OCT, CLE allows high-resolution optical imaging of microscopic tissue architecture with a 500-1000\(\times\) magnification, a sort of \"optical biopsy\" that can give real-time information, allowing the clinician to discriminate the tissue microstructures of single cells, aiming for the distinction between low-grade and high-grade BCa areas and to ensure the complete exportation of nonvisible tumors. This can have an important impact to ensure the completeness of TURBT and to facilitate patients' follow-ups, as it can dramatically reduce the false-negative cystoscopy rate. Moreover, the actual availability of a validated image atlas [14] allows clinicians to provide a uniform interpretation of CLE imaging, therefore standardizing the technique and allowing the creation of dedicated formation programs and specific on-line courses. The advantages of CLE have already been validated and confirmed in clinical practice in other specialities, such as in gastroenterology for colorectal polyposis/cancer discrimination, in superficial gastric dysplasia/cancer, and in [PERSON]'s esophagus [27; 28].