Comparison between intravesical and oral administration of 5‐aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer

Abstract

BACKGROUND: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5-aminolevulinic acid (ALA) (ALA-PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA-PDD (PDD-TURBT) for nonmuscle invasive bladder cancer. METHODS: Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA-induced fluorescence with the pathological result. PDD-TURBT was performed in 99 completely resectable cases corresponding to 210 ALA-PDD cases. To evaluate the abilities of PDD-TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT. RESULTS: The diagnostic accuracy and capability of ALA-PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA-PDD. The recurrence-free survival rate in the cases that underwent PDD-TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD-TURBT (hazard ratio, 0.578; P ¼ .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence-free survival. All procedures were well tolerated by all patients without any severe adverse events. CONCLUSIONS: This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA-PDD and PDD-TURBT are remarkably helpful in detection and intraoperative navigation programs.

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

“…PpIX has another property, which is its accumulation in tumor cells, and augmented red fluorescence results in the identification of tumor cells. Its emission of red fluorescence and accumulation in tumor cells are fundamental for PDD [16][17][18].…”

Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study

“…Currently, in Western countries, PDD by transurethral administration of a hexalated form of 5-ALA, 5-ALA hexyl ester (HAL), is performed as a routine medical practice. In Japan, Inoue et al [10] initiated a clinical study on the usefulness of 5-ALA in 2004, and obtained the outcome similar to those in studies performed overseas. Based on this our previous clinical study, we planned an investigator-initiated clinical trial with the aim of acquiring pharmaceutical approval.…”

“…The agent was approved for sale as an internal diagnostic drug for malignant glioma surgery in 2007 by the European Medicine Agency and in 2013 by Pharmaceuticals and Medical Device Agency in Japan where Nobelpharma and SBI Pharmaceuticals sell this agent for malignant glioma [10]. Based on these findings and in consideration of safety, 20 and 10 mg/kg were set to investigate the optimum dose for Japanese patients.…”

Photodynamic Diagnostic Ureterorenoscopy with Orally Administered 5-Aminolaevulinic Acid as Photosensitiser: How I Do It

“…Inoue et al [14] reported that the use of oral 5-ALA is just as effective as intravesical instillation.…”