The clinical trial on the safety and effectiveness of the photodynamic diagnosis of non-muscle-invasive bladder cancer using fluorescent light-guided cystoscopy after oral administration of 5-aminolevulinic acid (5-ALA)

Photodiagnosis Photodyn Ther. 2016 Mar:13:91-96. doi: 10.1016/j.pdpdt.2015.12.011. Epub 2016 Jan 2.

Abstract

Objective: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy.

Methods: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source.

Results: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body.

Conclusions: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.

Keywords: 5-Aminolevulinic acid (5-ALA); Carcinoma in situ (CIS); Non-muscle invasive bladder cancer (NMIBC); Photodynamic diagnosis (PDD); The advanced medical technology.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid / administration & dosage*
  • Aminolevulinic Acid / adverse effects
  • Contrast Media / administration & dosage
  • Cystoscopy / adverse effects
  • Cystoscopy / methods*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Japan
  • Male
  • Microscopy, Fluorescence / methods*
  • Middle Aged
  • Muscle, Smooth / pathology
  • Neoplasm Invasiveness
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / adverse effects
  • Surgery, Computer-Assisted / adverse effects
  • Surgery, Computer-Assisted / methods*
  • Treatment Outcome
  • Urinary Bladder Neoplasms / diagnostic imaging*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery*

Substances

  • Contrast Media
  • Photosensitizing Agents
  • Aminolevulinic Acid