# Confocal Laser Endomicroscopy for Bladder Cancer Detection: Where Do We Stand?
## 4 Discussion
### CLE Advantages for BCa Management  
One of the principal limitations of WLC is the inability to directly discriminate hyper-emic flat areas suspicious for carcinoma in situ (CIS), which can be missed or confounded with inflammation. CLE provides clear advantages for those situations, as shown in the examined papers. The reliability of CLE imaging has been provided in the studies reported in this SR. [PERSON] et al. [18] reported that the correspondence of CLE imaging plus WLC evaluation corresponded to the final histological diagnosis in 81% of cases, even without a previous clinical experience on CLE utilization. Another important application of CLE relates to the detection of carcinoma in situ (CIS) in lesions, which are often misdiagnosed by WLC. The only work that addresses this argument is the one by [PERSON] et al. [17] in which the authors reported the comparison between 21 CIS cases analyzed by CLE and the subsequent biopsies, compared to a similar group of \"non-CLE\" ones, reporting a CIS detection rate of 83.3%, which is almost 20% higher than on WLC alone; it is also important to state that CIS microscopic features are variable, as a cellular layer can be completely flat or present a thickening of the urothel. This can bias image interpretation; therefore, a specific formation on CLE image interpretation is also crucial to optimize the CLE detection rate. According to the authors of [17], the CLE aspects of CIS appeared presented more pleomorphic and large cells compared with inflammatory lesions with extensive acellular areas and indistinct cell borders. However, CIS cases are not reported on further in other series, and this should be a main theme for future investigations. Moreover, CLE can provide significant advantages in the diagnostic assessment of BCa, allowing a clear and real-time recognition of small and low-grade tumors that can be treated by office fulguration instead of needing a surgical retrieval and histologic exam. This statement is outlined in the paper by [PERSON] et al. [20]. According to those authors, this could potentially shift the treatment of those lesions, with a reduction in surgical load, waiting lists for surgery, and medical costs for hospitalization, also avoiding the potential complications of TURBT. This is also outlined as the greatest advantage of CLE in the paper by [PERSON] et al. [21], even if the authors outline that further improvements in imaging processing are still needed to address this statement (see CLE Limitation Section 4.3). In fact, CLE-pooled sensitivity and specificity for low-grade urothelial carcinomas resulted 0.72 and 0.87, respectively, while it is 0.82 and 0.84, respectively, for high-grade ones. Thus, the false-negative rate for high-grade lesions is still too high to make this technique comparable to a histologic report, as there is the risk of missing potential high-grade tumors. However, CLE can have a role in verifying surgical radicality after TURBT, ensuring the presence of detrusor muscle in the resection specimens with clear benefit for the patient and reducing the needs for an early repeated TURBT. Another possible application of CLE is in combination with other optical imaging techniques like PDD, NBI, or OCT in view of a multimodal optical assessment. Even if interesting, the feasibility of combining two or more techniques is limited by the technical requirements (need of different cystoscopes, light filters, probes, and devices) [31]. However, there are already different reports in the literature that introduce the concept of \"multiparametric cystoscopy\" combining the information delivered from the different diagnostic tools available and validating it for clinical use. [PERSON] et al. [32] tested real-time multispectral imaging combining the imaging derived from WLC, PDD, and different enhanced vascular imaging technologies in 31 patients with suspected BCa. Another important study in this field is the one by [PERSON] et al.