# Confocal Laser Endomicroscopy for Bladder Cancer Detection: Where Do We Stand?
## 4 Discussion
### CLE Limitations  
Even if promising, CLE is still a new-coming device in clinical practice and only three papers [18; 19; 20] report a series including up to 50 patients. Moreover, only two papers have been published in the last three years. In fact, five papers were already present before the publication by [PERSON] et al. of the SR [34] with the same argument. This can be partially explained by the advent of the COVID-19 pandemic, which has slowed down many clinical activities, but it is also related to the actual limitations of CLE imaging for BCa diagnosis. The first is a technical one intrinsic to the probe, as the CLE probe needs a perpendicular contact with the bladder mucosa for image caption and delivering, which is not possible for lesions located in the anterior zone of the bladder [16]. Moreover, the probe is subjected to motion artefacts related both to the patient or the operator, and this can impair the quality of registration.  
Afterward, CLE imaging needs a correct interpretation, and this could create a bias among readers, as stated before. This suggests the need of structured training before starting CLE image interpretation in a clinical practice. Moreover, a greater amount of data regarding the CLE imaging of bladder tumors should be provided by multicenter studies to further validate image assessment and interpretation.  
The recent study by [PERSON] et al. [21] outlines that even if CLE in its actual form has a high negative predictive value (81% in this study), it is not still capable of being a potential substitute of histologic examination, especially for HG tumors, where a misdiagnosis can negatively affect the natural history of the disease. Therefore, further studies are needed to implement CLE accuracy and imaging interpretation before it can be presented as a possible alternative to histologic examination of retrieved specimens after TURBT. Specific tutoring through video sessions and real-time assessment tests are therefore further encouraged to improve the CLE image interpretations, as stated in the analyzed studies. Another potential solution, according to [PERSON] et al. [17], can be the validation of a dedicated software able to automatically acquire CLE imaging, delivering a video sequence of the bladder mucosa, which can allow an easier and more correct interpretation of CLE in contrast to a single image. This can reduce interobserver interpretation variability; however, it can also be potentially biased by software limitations.  
Other limitations of the application in clinical practice are the cost-effectiveness of the method in comparison to WLC and the availability of CLE probes, which limit CLE's current application only to clinical trials with defined protocols. However, a potential reduction in misdiagnosis through improved diagnostic accuracy could easily overcome this statement and this has already been documented for other diseases in the literature [35]. Thus, we predict a constant increase in CLE imaging adoption in clinical settings in the near future, in parallel to the technical amelioration of fluorescent contrast and probe technology.