Grading urothelial carcinoma with probe-based confocal laser endomicroscopy during flexible cystoscopy

Abstract Purpose Urothelial bladder cancer (UCB) care requires frequent follow-up cystoscopy and surgery. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic evaluation with the potential for outpatient grading of UCB. This study aims to investigate the diagnostic accuracy and interobserver variability for the grading of UCB with CLE during flexible cystoscopy (fCLE). Methods Participants scheduled for transurethral resection of papillary bladder tumors were prospectively included for intra-operative fCLE. Exclusion criteria were flat lesions, fluorescein allergy or pregnancy. Two independent observers evaluated fCLE, classifying tumors as low- or high-grade urothelial carcinoma (LGUC/HGUC) or benign. Interobserver agreement was calculated with Cohens kappa (κ) and diagnostic accuracy with 2 × 2 tables. Histopathology was the reference test. Results Histopathology of 34 lesions revealed 14 HGUC, 14 LGUC and 6 benign tumors. Diagnostic yield for fCLE was 80–85% with a κ of 0.75. Respectively, sensitivity, specificity, NPV and PPV were: for benign tumors 0–20%, 96–100%, unmeasureable-50% and 87%, for LGUC 57–64%, 41–58%, 44–53% and 54–69% and for HGUC 38–57%, 56–68%, 38–57% and 56–68%, with an interobserver agreement of κ 0.61. Conclusion fCLE is currently insufficient to grade UCB.