The patients are placed in the extended lithotomy position and sterile draped and a transurethral catheter (16 Ch) is inserted (figure 2). Figure 2 Patient placed this website in extended lithotomy position with transperineally inserted electrodes using brachytherapy grid under ultrasound guidance. The surgeon will assign the patients to two parallel groups. One

group will have a focal ablation of the prostate; the other group will receive an extended ablation. In this way, we are able to assess the side effects of electroporation with different treatment scenarios. In grouping the patients, the tumour position will be taken into account monitored by preceding biopsies, MRI and CEUS. Therefore, mainly the tumour will be treated but also a part of surrounding healthy prostate tissue.

The effects and the safety of the technique on both the tissues will be observed. To define the treatment area, a biplane transrectal ultrasound system (Amsterdam Hi Vision Preirus, Hitachi Medical Systems, The Netherlands, equipped with an endocavity probe, type EUP-U533, C8.0–4.0, L10.0-5.0; Athens 2102 Falcon and 2202Pro Focus, BK Medical, Denmark, equipped with an endocavity probe models 8658 and 8848) will be used to visualise the prostate in sagittal and axial direction. The volume and shape of the prostate will be determined. These data will be entered into the planning software system. The specified area will be chosen for ablation. Two up to six 19-gauge unipolar electrode needles will be inserted transperineally using a brachytherapy grid under continuous ultrasound guidance (figures 3 and ​and44). Figure 3 Three electrodes transperineally inserted through a brachytherapy grid. Figure 4 Transrectal ultrasound image with three inserted electrodes in right prostate lobe. For an extended ablation with >4 electrodes, 2 electrodes will be repositioned followed by a second IRE

course including the 4 electrodes in place. The locations will be verified using sagittal and axial ultrasound images of the prostate. Minimal distances between the needles and between the needles and essential structures (urethra, bladder neck, capsule and rectum) will be measured by ultrasound. The data will be transferred to the build-in planning software of the NanoKnife IRE device (figure 5). Figure 5 Planning software with localisation of two needles (green numbered circles). Entinostat The ablation procedure uses 90 pulses of 90 μs duration each with an electric field of 1500 V/cm between an electrode pair. Electric pulses are delivered between each of the electrode pairs. The actual treatment time will be approximately 5–10 min whereas the whole procedure is scheduled for 60 min. Ethics and dissemination Data will be presented at international conferences and published in peer-reviewed journals.