Marieke van Son

15 GENERAL INTRODUCTION AND THESIS OUTLINE mp-MRI is the best technique to evaluate local recurrence(78). Available whole-gland salvage treatments include salvage RP, cryotherapy, HIFU and brachytherapy. Although salvage RP and HIFU are associated with worse rates of urinary incontinence (40-50%) than salvage cryotherapy or brachytherapy (7-12%), all modalities have high impotence rates (±75%) and high rates of urethral stricture (±20%). Reported overall relapse rates are similar across all treatments, with 45-55% of patients experiencing post-salvage recurrence after 4.5 years(79). Due to these unfavorable oncologic and functional out- comes, ±90% of patients with radiorecurrent disease is currently treated with ADT(80). Introduction to focal therapy To reduce the burden of treatment-related side-effects, preservation of normal pros- tate tissue and surrounding structures is warranted. Focal therapy, which entails the targeted ablation of only the malignant area of the prostate, has been suggested as a way to accomplish this(81). However, efforts to adopt a focal therapy approach for prostate cancer have been challenged by the multifocal nature of the disease, with only 20-30% of men having unifocal or unilateral cancer(82). Figure 5: Monoclonal origin of metastatic prostate cancer. Adapted from: Liu et al., 2009 (81) Despite the notion of multiple lesions harboring clones of cancer cells, considerable evidence suggests that one lesion in the prostate (the index lesion or dominant intra- prostatic lesion) may be the most important predictor for the course of the disease and its prognosis(83). Furthermore, genetic studies on pathologic characteristics of metastatic prostate cancer indicate that a single precursor cell from one type of clone could be responsible for driving the cancer to metastasize and become lethal 1