Oral 5-aminolevulinic acid-mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A multicenter phase III study

Int J Urol. 2018 Aug;25(8):723-729. doi: 10.1111/iju.13718. Epub 2018 Jul 12.

Abstract

Objective: To confirm the reproducibility of the effectiveness and safety in photodynamic diagnosis of non-muscle-invasive bladder cancer using 5-aminolevulinic acid in a prospective multicenter non-randomized phase III trial.

Methods: A total of 61 patients with primary or recurrent non-muscle-invasive bladder cancer were prospectively enrolled from five hospitals between May 2015 and March 2016. 5-Aminolevulinic acid (20 mg/kg) was orally administered 3 h before transurethral resection of bladder tumors using white light or fluorescent light. Of 60 evaluable patients, 511 specimens were obtained from tumor-suspicious lesions and normal-looking mucosa. The primary end-point was sensitivity. The secondary end-points were specificity, positive and negative predictive values, and safety.

Results: The sensitivity of the fluorescent light source (79.6%) was significantly higher (P < 0.001) than that of the white light source (54.1%). In total, 25.4% (46/181) of tumor specimens were diagnosed as positive with only the fluorescent light source. In nine (15%) of 60 patients, the risk classification and recommended treatment after transurethral resection of bladder tumors were changed depending on the additional types of tumor diagnosed by the fluorescent light source. The specificity of the fluorescent light versus white light source was 80.6% versus 95.5%. No grade 4-5 adverse event was noted. Hypotension and urticaria were severe adverse events whose relationship to oral 5-aminolevulinic acid could not be excluded.

Conclusions: These findings confirm the diagnostic efficacy and safety of photodynamic diagnosis with 20 mg/kg of oral 5-aminolevulinic acid, and show that transurethral resection of bladder tumors with a fluorescent light source using oral 5-aminolevulinic acid is well tolerated.

Keywords: 5-aminolevurlinic acid; non-muscle-invasive bladder cancer; oral intake; photodynamic diagnosis; transurethral resection.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid / administration & dosage*
  • Aminolevulinic Acid / adverse effects
  • Carcinoma in Situ / diagnosis*
  • Carcinoma in Situ / pathology*
  • Carcinoma in Situ / surgery
  • Cystoscopy / methods
  • Female
  • Fluorescence
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / adverse effects
  • Prospective Studies
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery

Substances

  • Photosensitizing Agents
  • Aminolevulinic Acid