Vascular-targeted photodynamic therapy (padoporfin, WST09) for recurrent prostate cancer after failure of external beam radiotherapy: a study of escalating light doses.

Abstract

To report on the efficacy of TOOKAD (WST 09; NegmaLerads, Magny-Les-Hameaux, France) vascular-targeted photodynamic therapy (VTP) as a method of whole-prostate ablation in patients with recurrent localized prostate cancer after the failure of external beam radiotherapy (EBRT). Patients received a fixed photosensitizer dose of 2 mg/kg and patient-specific light doses as determined by computer-aided treatment planning. Up to six cylindrical light-diffusing delivery fibres were placed transperineally in the prostate under ultrasonographic guidance. The treatment response was assessed by measuring serum prostate-specific antigen (PSA) levels, lesion formation (avascular areas of tissue) measured on 7-day gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) and a 6-month biopsy. Treatment of the whole prostate was possible with minimal effects on surrounding organs. An increased light dose improved the tissue response, with MRI-detectable avascular lesions, encompassing up to 80% of the prostate in some patients. A complete response, as determined by the 6-month biopsy, required that patients received light doses of at least 23 J/cm(2) in 90% of the prostate volume (D(90) > 23 J/cm(2)). Of the 13 patients who received at least this light dose, eight were biopsy-negative at 6 months. In this group of eight patients, PSA levels decreased and did so to negligible levels for those patients with a baseline PSA level of <5 ng/mL. Side-effects were modest and self-limited in most patients; there were recto-urethral fistulae in two patients, one of which closed spontaneously. TOOKAD-VTP can produce large avascular regions in the irradiated prostate, and result in a complete negative-biopsy response at high light doses. A response rate of more than half for those patients receiving the highest light doses shows the clinical potential of TOOKAD-VTP to manage recurrence of prostatic carcinoma after EBRT.