Original article Photodynamic Therapy of Bladder Cancer – A Phase I Study Using Hexaminolevulinate (HAL)  M. J. Bader, M.D. a,b, * 1 , Herbert Stepp, Ph.D. b,1 , Wolfgang Beyer, Ph.D. b , Thomas Pongratz b , Ronald Sroka, Ph.D. b , Martin Kriegmair, M.D. c , Dirk Zaak, M.D. d , Mona Welschof, Ph.D. e , Derya Tilki, M.D. a , Christian G. Stief, M.D. a , Raphaela Waidelich, M.D. a a Department of Urology, Ludwig Maximilians Universität München, Campus Grohadern, Munich, Germany b Laser Research Laboratory, LIFE Center, Ludwig Maximilians Universität München, Campus Großhadern, Munich, Germany c Urology Clinic Dr. Castringius Munich-Planegg, Planegg, Germany d Urology Clinic Traunstein, Traunstein, Germany e Photocure ASA, Oslo, Norway Received 23 December 2011; received in revised form 9 February 2012; accepted 9 February 2012 Abstract Objectives: To assess the safety and feasibility of hexaminolevulinate (HAL) based photodynamic therapy (PDT) as adjuvant treatment after transurethral resection of the bladder (TURB) in patients with intermediate or high-risk urothelial cell carcinoma (UCC) of the bladder. Materials and methods: Seventeen patients received 50 ml of either a 16 mM (4 patients) or 8 mM HAL (13 patients) solution instilled intravesically. Bladder wall irradiation was performed using an incoherent white light source coupled via a quartz fiber assembled into a flexible transurethral irrigation catheter. Each patient received 3 treatments with HAL-PDT 6 weeks apart. After PDT, patients were followed by regular cystoscopy for up to 21 months to assess time to recurrence. Reported adverse events (AEs) were coded according the World Health Organization Adverse Reaction Terminology (WHO-ART). Efficacy was assessed by cystoscopy, cytology, and histology, and was defined as the number of patients who were tumor-free at 6 or 21 months after initial PDT treatment. Transient bladder irritability was reported by 15 of the 17 patients and resolved completely in all patients. No evidence of a cumulative effect of treatment on the incidence of AEs could be detected. PDT treatment was performed without any technical complications. Furthermore preliminary assessment of efficacy showed that of the 17 patients included, 9 (52.9%; 95% CI: 27.8 –77.0) were tumor-free at 6 months, 4 (23.5%; 95% CI: 6.8 – 49.9) were tumor-free at 9 months, and 2 (11.8%, 95% CI: 1.5–36.4) were tumor-free after 21 months. Conclusions: PDT using hexaminolevulinate and an incoherent white light system with the special flexible irradiation catheter system is technically feasible and safe and may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer. © 2013 Elsevier Inc. All rights reserved. Keywords: Bladder cancer; Photodynamic therapy; Hexaminolevulinate; Protoporphyrin fluorescence 1. Introduction Non-muscle-invasive bladder cancer is currently treated by transurethral resection (TURB) and/or fulguration. How- ever, recurrence and progression rates following endoscopic treatment of visible lesions are significant. The probabilities of recurrence range from about 15% to 61% at 1 year and from 31% to 78% at 5 years; the progression rate ranges from about 1% to 17% at 1 year and from 1% to 45% at 5 years [1]. To prevent recurrent and progressive disease, adjuvant intravesical chemotherapy and immunotherapy are applied. There is also rising interest in new therapeutic strategies such as photodynamic therapy (PDT). PDT has been shown to be effective in even bacillus Calmette-Guerin (BCG) refractory UCC and might offer a potential alterna- tive for patients indicated for cystectomy [2]. The PDT mechanism relies on a specific light interaction with a photosensitized target tissue. The first generation  This work was supported by Photocure ASA, Oslo, Norway, Karl Storz GmbH and Co. KG, Tuttlingen, Germany, and OptiMed GmbH, Ettlingen, Germany. * Corresponding author. Tel.: +00498970952971; fax: +00498970955444. E-mail address: markus.bader@med.uni-muenchen.de (M.J. Bader). 1 These authors contributed equally to this work. Urologic Oncology: Seminars and Original Investigations 31 (2013) 1178 –1183 1078-1439/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.urolonc.2012.02.007