Comparative Effectiveness of Fluorescent Versus White Light Cystoscopy for Initial Diagnosis or Surveillance of Bladder Cancer on Clinical Outcomes: Systematic Review and Meta-Analysis

Purpose: We systematically reviewed the comparative effectiveness of fluorescent vs white light cystoscopy on bladder cancer clinical outcomes. Materials and Methods: Systematic literature searches of Ovid MEDLINE (R) (January 1990 through September 2015), Cochrane databases and reference lists were performed. A total of 14 randomized trials of fluorescent cystoscopy using 5-aminolevulinic acid or hexaminolevulinic acid vs white light cystoscopy for the diagnosis of initial or recurrent bladder cancer that reported bladder cancer recurrence, progression, mortality and harms were selected for review. Results: Fluorescent cystoscopy was associated with a decreased risk of bladder cancer recurrence vs white light cystoscopy at short-term (less than 3 months, 10 trials, RR 0.59, 95% CI 0.40 to 0.88, I-2 =69%), intermediate-term (3 months to less than 1 year, 6 trials, RR 0.70, 95% CI 0.56 to 0.88, I(2=)19%) and long-termfollowup (1 year or more, 12 trials, RR 0.81, 95% CI 0.70 to 0.93, I(2=)49%). However, the findings were inconsistent, and potentially susceptible to performance and publication bias (strength of evidence low). There were no differences between cystoscopic methods in risk of mortality (3 trials, RR 1.28, 95% CI 0.55 to 2.95, I(2=)41%) (strength of evidence low) or progression (9 trials, RR 0.74, 95% CI 0.52 to 1.03, I(2=)0%) (strength of evidence moderate). Estimates for short-termrecurrence (6 trials, RR 0.62, 95% CI 0.38 to 1.00), long- term recurrence (7 trials, RR 0.75, 95% CI 0.62 to 0.92) and progression (4 trials, RR 0.51, 95% CI 0.28 to 0.96) were statistically significant in the subgroup of trials that used hexaminolevulinic acid, but there were no statistically significant interactions based on the photosensitizer used. Fluorescent cystoscopy was not associated with a decreased risk of long- term recurrence in 3 trials that used methods to reduce performance bias with initial cystoscopy (RR 0.96, 95% CI 0.79 to 1.18, I(2=)36%). Data on harms were sparse. Conclusions: Fluorescent cystoscopy was associated with a reduced risk of bladder cancer recurrence vs white light cystoscopy. However, additional trials that adequately guard against performance bias are needed to confirm these findings. Fluorescent cystoscopy with hexaminolevulinic acid may be associated with a decreased risk of progression, but more studies with long- term followup are needed to better understand the effects of the photosensitizer used on progression.