The Accuracy of Confocal Laser Endomicroscopy in Diagnosing Bladder Cancer: A Systematic Review & Meta-Analyses

Background: Multiple advancements of endoscopic technology were designed to enhance the sensitivity and specificity of the diagnostic tools of bladder cancer; thus, we perform a meta-analysis to compare diagnostic performance between confocal laser endomicroscopy (CLE) and biopsy for detecting bladder cancer.Methods: We compared CLE’s accuracy in diagnosing bladder cancer reported by studies obtained from the electronic database MEDLINE, CENTRAL, and CINAHL, from May to June 2020. The pooled effect estimate was calculated employing the DerSimonian and Laird random-effects model. We only included moderate to high-quality studies, which had been assessed by the QUADAS-2 tool.Results: Eight studies were included in this review; five of those were good-quality studies. A total of 519 samples from 345 patients were included in the pooled effect estimate calculation. Pooled sensitivity and specificity of CLE in diagnosing bladder cancer were 90.2% (0.86, 0.93) and 78.1% (0.71, 0.85), respectively. The use of white-light cystoscopy (WLC) before CLE increased its specificity (56.8% versus 84.6%). Pooled sensitivity and specificity of CLE in predicting lowgrade lesion were 73% (0.66, 0.80) dan 83% (0.78, 0.87), respectively. Meanwhile, pooled sensitivity and specificity of CLE in predicting high-grade lesion were 73% (0.66, 0.78) and 79% (0.73, 0.83), respectively.Conclusions: CLE has good accuracy in distinguishing malignant and benign tumors. Grading tumors with this modality is also accurate. The use of probe CLE (pCLE), coupled with WLC, will increase its specificity.

Performance of Narrow Band Imaging (NBI) and Photodynamic Diagnosis (PDD) Fluorescence Imaging Compared to White Light Cystoscopy (WLC) in Detecting Non-Muscle Invasive Bladder Cancer: A Systematic Review and Lesion-Level Diagnostic Meta-Analysis

Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.

REVIEW OF DIAGNOSTIC OPPORTUNITIES FOR IMPROVEMENT OF DETECTION OF NON-MUSCLE INVASIVE BLADDER CANCER

Recently white light cystoscopy (WLC) is the standard method for detection of urothelial cell carcinoma of the bladder. Regarding the problem that on the one hand the sensitivity of WLC is not high enough, and on the other hand it can miss small ‘satellite’ tumors or carcinoma in situ (CIS), other techniques are used. Such techniques are the new imaging by photodynamic diagnosis (PDD) and narrow band imaging (NBI). The both techniques allow very accurate bladder cancer visualization. It is obviously very important to improve diagnostic accuracy and as consequence it increases the quality of resection. Regarding the meta-analysis of several studies, it can be concluded that the new imaging techniques should be applied for a more precise diagnostic, comparing with WLC. Further results of multicentric meta-analysis between these two techniques will stabilize their advantages for concrete clinical indications.

Comparison of Recurrence of Non-muscle Invasive Bladder Carcinoma after Transurethral Resection with Hexaminolevulinate Photodynamic Diagnosis or Regular Cystoscopy

Purpose: Comparison of recurrence of non-muscle invasive bladder carcinoma after transurethral resection with hexaminolevulinate photodynamic diagnosis (PDD) or regular white light cystoscopy (WLC).Methods: We included patients with newly suspected non-muscle invasive bladder carcinoma in this retrospective cohort study and compared those undergoing transurethral resection by WLC and PDD. The primary outcome was the difference in the recurrence rate after 60 months’ follow-up, but we also stratified recurrence by risk groups. The mean recurrence-free survival was compared between the cohorts. Odds ratios or hazard ratios are reported with 95% confidence intervals.Results: The WLC and PDD cohorts comprised 124 and 91 subjects, respectively. There were no significant differences in recurrence rates at 6 months (recurrence rate 9/123; 7.3%), 12 months (17/118; 14.4%), or 60 months (39/102; 38.2%), with odds ratios of 1.23 (0.48–3.25; P=0.64), 1.32 (0.67–2.62; P=0.42), and 1.12 (0.70–1.79; P=0.65), respectively. Further analysis showed no significant effect of PDD on recurrence by risk group or on mean recurrence-free survival (hazard ratio, 1.12; 0.70–1.79).Conclusion: Photodynamic diagnosis with hexaminolevulinate did not reduce the recurrence of non-muscle invasive bladder carcinoma compared to standard white light cystoscopy when used for transurethral resection.

First results of computer-enhanced optical diagnosis of bladder cancer

Bladder cancer is the sixth leading cancer cause worldwide. Non-muscle invasive tumors can be diagnosed and treated endoscopically. Based on biopsies alone, pathologists cannot determine the spatial organization of specimens, their relationship with each other, or their complete removal. To extend white light cystoscopy as the gold standard for bladder cancer detection, diagnosis and removal of small or flat lesions, new image-based technologies have been investigated. These include a stereo-cystoscope for improved orientation and navigation, computation of 2D and 3D panoramic images for extended visualization and documentation, as well as label-free fiber-based fluorescence-lifetime imaging (FLIM) and Raman-spectroscopy in combination with statistical data analysis. Combining all these technologies, cystoscopy can will be further enhanced to include new diagnostic possibilities.

Raman Spectroscopy to Characterize Bladder Tissue for Multidimensional Diagnostics of Cancer in Urology

Fiber optic Raman spectroscopy offers labelfree identification of cancer in the bladder under in vivo conditions. However, state-of-the-art Raman technology does not enable to scan the entire bladder wall. Our multidimensional approach within the project Uro-MDD combines panoramic 3D-image reconstruction of white light cystoscopy and fluorescence lifetime imaging to define regions of interest for Raman-assisted diagnostics. First Raman results are presented from human control and cancer bladder specimens that demonstrated how to obtain specific molecular information. Such Raman images can be used in a clinical setting to determine cancer margins and the resection status. Fiber probes are under development to translate the technique to in vivo screening.