How to Avoid Local Side Effects of Bladder Photodynamic Therapy: Impact of the Fluence Rate

Purpose: We studied how to avoid irritative bladder symptoms after bladder photodynamic therapy, such as urgency, frequency and pain, which are associated with the inflammation and destruction of normal urothelium. Materials and Methods: Rats bearing orthotopic bladder tumors were instilled with hexyl-aminolevulinate and illuminated with red light at a high vs low (100 vs 15 mW/cm(2)) fluence rate. Cystectomy specimens 48 hours after treatment were subjected to anatomopathological examination. Inflammatory reaction and apoptosis were evaluated. In vivo photobleaching was assessed during illumination at each fluence rate. Results: All superficial tumors were eradicated irrespective of light dose and fluence rate. High fluence rates induced necrosis with inflammatory reaction and absent normal urothelium. Low fluence rates did not provoke inflammation and resulted in apoptotic cell death with preserved urothelial integrity. This could be attributable to faster photobleaching of the photosensitizer in normal urothelium at low fluence rates. Conclusions: Bladder photodynamic therapy at a low fluence rate minimizes side effects without hampering therapeutic efficacy.