Pendsé, DA; (2012) Photodynamic Therapy and Focal Therapy for Prostate Cancer. Doctoral thesis , UCL (University College London).

Abstract

Prostate Cancer is the most commonly diagnosed cancer in men. The incidence of prostate cancer has risen over the last two decades, although mortality rates have not increased to the same extent. For many men with localised prostate cancer the choice of treatment lies between radical surgery or radiotherapy and active surveillance. Evidence suggests that the survival benefits related to radical treatment are small, and that conservative management may be appropriate for many men. A strategy of focal therapy in prostate cancer aims to treat tumour foci within the prostate, without treating the whole gland, with a resultant reduction in side-effects. Photodynamic therapy (PDT) is the use of a photosensitising drug, which when activated by light can cause cellular damage. Tookad is a new-generation photosensitiser, which is activated in vasculature. Phase I and II clinical trials of Tookad PDT in men with recurrent prostate cancer following radiotherapy have been performed. These studies show that it is possible to ablate prostate tissue with Tookad PDT. This thesis describes a phase I/II clinical trial evaluating the safety and efficacy of Tookad PDT in men with primary prostate cancer. Treatments were performed under general anaesthetic, using 2mg/kg Tookad and interstitial light delivery via cylindrical diffuser fibres. 15 patients were included in part A (single-fibre, light-dose-escalation), 19 patients in part-B (multi-fibre, focal and whole-gland ablation). Follow-up was for 12-months, with assessment of treatment effect made on MRI. Post-treatment imaging demonstrated that prostate tissue can be ablated in a reproducible and controlled manner with Tookad PDT. Although genitourinary side-effects were relatively few, significant cardiovascular complications in this study lead to early termination of the clinical trial and withdrawal of the drug. Results suggest that Tookad PDT could potentially deliver either focal or whole-gland therapy. Further studies with modified photosensitsers are underway.

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