Results of a prospective randomized study assessing the efficacy of fluorescent cystoscopy-assisted transurethral resection and single instillation of doxorubicin in patients with non-muscle-invasive bladder cancer

World J Urol. 2017 May;35(5):745-752. doi: 10.1007/s00345-016-1927-y. Epub 2016 Sep 7.

Abstract

Objectives: To assess the efficacy of two treatment options for non-muscle-invasive bladder cancer (NMIBC): (1) transurethral resection (TUR) guided by fluorescence cystoscopy (FC) with the use of 5-aminolevulinic acid (5-ALA) and (2) single early instillation of doxorubicin in a single-center open-label prospective randomized study with a 2 × 2 factorial design.

Patients and methods: Patients with clinical suspicion of primary or recurrent NMIBC were randomized into four study arms: FC-assisted TUR with 5-ALA and single instillation of doxorubicin, FC-assisted TUR without instillation, TUR in white light (WL) with single instillation of doxorubicin, and WL-TUR only. The study was designed to assess recurrence-free survival in arms with and without any of two interventions.

Results: Of 525 patients included, 377 (72 %) were eligible for primary outcome assessment. The median follow-up was 54.8 months. FC statistically significantly decreased the risk of disease recurrence and progression with hazard ratio (HR) 0.56 (95 % CI 0.39-0.80, p = 0.001) and 0.33 (95 % CI 0.12-0.91, p = 0.031), respectively. The HRs for recurrence and progression for single instillation of doxorubicin were 0.76 (95 % CI 0.54-1.07, p = 0.11) and 0.65 (95 % CI 0.28-1.52, p = 0.32), respectively. The overall and cancer-specific survival rates did not differ significantly based on the therapeutic interventions.

Conclusions: In patients with NMIBC, FC-assisted TUR with 5-ALA results in a substantial recurrence and progression risk reduction as compared to WL-TUR. The single early postoperative instillation of doxorubicin did not have a statistically significant impact on recurrence and progression risks.

Keywords: 5-Aminolevulinic acid; Fluorescence cystoscopy; Non-muscle-invasive bladder cancer; Single early instillation of chemotherapeutic drug.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravesical
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid
  • Antibiotics, Antineoplastic / therapeutic use*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / therapy*
  • Cystoscopy / methods*
  • Disease-Free Survival
  • Doxorubicin / therapeutic use*
  • Female
  • Fluorescence
  • Humans
  • Male
  • Middle Aged
  • Muscle, Smooth / pathology
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / epidemiology
  • Photosensitizing Agents
  • Proportional Hazards Models
  • Prospective Studies
  • Survival Rate
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • Antibiotics, Antineoplastic
  • Photosensitizing Agents
  • Doxorubicin
  • Aminolevulinic Acid