Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid

Abstract

OBJECTIVES: Tiny papillary tumors and flat urothelial lesions such as dysplasia or carcinoma in situ can easily be missed during routine cystoscopy. Various methods for in vivo detection of fluorescing agents (preferentially localized in malignant tissue) have been developed. Most of them are based on systemically administered synthetic porphyrin compounds and require sensitive detection devices and image processing units for fluorescence visualization. The usefulness of intracellularly accumulated endogenous protoporphyrin IX (PPIX), induced by 5-aminolevulinic acid (ALA), for diagnosis of early bladder cancer and the correlation with cystoscopic, microscopic, and fluorescence findings was investigated. METHODS: ALA was instilled intravesically in 68 patients, followed by fluorescence cystoscopy with violet light from a krypton ion laser that produced fluorescence excitation. There were 299 biopsies obtained from fluorescing and nonfluorescing areas of the bladder. RESULTS: ALA-induced fluorescence could be easily observed with the naked eye during cystoscopy under violet light illumination. All tumor lesions were sharply marked with brightly shining red fluorescence. Correlation of fluorescence and microscopic findings gave a sensitivity of 100% and a specificity of 68.5%. There were 26 malignant or precancerous lesions that were missed during routine cystoscopy but were detected only by ALA-induced fluorescence. CONCLUSIONS: Labeling of urothelial lesions by PPIX fluorescence induced by intravesically instilled ALA seems to be a promising diagnostic procedure for malignant lesions that are difficult to visualize with standard cystoscopy.