Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study

J Urol. 2018 May;199(5):1158-1165. doi: 10.1016/j.juro.2017.11.096. Epub 2017 Dec 2.


Purpose: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance.

Materials and methods: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy.

Results: Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious.

Conclusions: Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.

Trial registration: ClinicalTrials.gov NCT02560584.

Keywords: bladder neoplasms; carcinoma in situ; cystoscopy; local; neoplasm recurrence; optical imaging.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid / analogs & derivatives*
  • Cystoscopy* / adverse effects
  • Cystoscopy* / instrumentation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Photosensitizing Agents*
  • Prospective Studies
  • Urinary Bladder Neoplasms / diagnosis*


  • Photosensitizing Agents
  • Aminolevulinic Acid
  • 5-aminolevulinic acid hexyl ester

Associated data

  • ClinicalTrials.gov/NCT02560584