Sequential whole bladder photodynamic therapy treatments: A preclinical study

Abstract

We postulated that sequential whole bladder photodynamic therapy (WBPDT) treatments with a low WBPDT dose would result in improved safety profile and good local tumor control. However, the drawback with such a proposal is the potential cumulative effect of sequential WBPDT treatments on bladder function. We designed this preclinical study to determine the safety of sequential WBPDT treatments. Six female dogs underwent a single WBPDT treatment comprising 1.5 mg/kg of Photofrin® and 15 J/cm 2 of light. Four dogs received a second treatment; and three dogs received three treatments. Pre- and post-WBPDT evaluations included cystoscopy and saline cystometry at baseline, 1 week, and 12 weeks. Gross and histopathologic analysis of cystectomy specimens occurred at 1 and 12 weeks. A single photodynamic therapy (PDT) treatment induced average bladder capacity losses of 11% (0–33) and 0% at post-WBPDT weeks 1 and 12, respectively. A second sequential WBPDT treatment caused average bladder capacity losses of 36% (0–57%) and 17% (2–24%) at weeks 1 and 12, respectively. Three sequential WBPDT treatments induced average bladder capacity losses of 22% (0–42) and 0% at weeks 1 and 12, respectively. Full recovery in bladder capacity occurred in all cases except after the second sequential treatment, which induced a persistent bladder capacity loss of 17% at 12 weeks. Histopathologic analysis of cystectomy specimens revealed a focal discernible injury to the superficial muscle in only one of the dogs that received three treatments. We conclude that sequential WBPDT treatments using low dose PDT Photofrin® (1.5 mg/kg and light ≤15 J/cm 2) is safe, and we recommend using this low WBPDT dose in clinical investigation.