[Clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder cancer]

Abstract

Purpose: To report our clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and to assess any side-effects of the diagnostic method.

Materials and methods: Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4 women with a median age of 71 years (range 44-84), 7 were primary cases and 11 were recurrent cases with bladder cancer. Two to two and half hours prior to endoscopy 1.5 g 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K. K.) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. The levels in images of the 5-aminolevulinic acid-induced fluorescence were compared with the pathological results. The area under the receiver operative characteristic (ROC) curve (AUC) in blue light endoscopy was also compared with that in white light endoscopy.

Results: Among the 129 specimens obtained by transurethral biopsy 45 were obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76 malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were detected pathologically, with a sensitivity of 89.5% and specificity of 58.5% with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more than that in white light endoscopy in not only all cases (p = 0.010) but also in cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002). Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did not seem to affect the accuracy of photodynamic diagnosis. Procedures were well tolerated by all patients with mild bladder irritability but no systemic side effect.

Conclusion: Photodynamic diagnosis with intravesically applied 5-ALA is more effective than observation by conventional cystoscopy in detecting bladder cancer without additional risk or complication, and is expected to become a golden standard in the detection program.