This insurance provides cover for damage to research participants through injury or death caused by the study (€450 000 for death or injury for each participant who participates in the research; €3 500 000 for death or

injury for all paticipants who participate in the research; €5 000 000 for the total damage incurred by the organisation for all damage disclosed during by scientific research for the investigator in the meaning of said Act in each year of insurance coverage). Discussion This will be the largest study cohort on IRE pre-RP. Previously, Neal et al described two human IRE cases performed without serious adverse events followed by uncomplicated radical prostatectomies. The histology shows tissue necrosis plus a variable extent of reactive stromal fibrosis, inflammatory infiltrates and regenerative changes in epithelial lining of prostatic ducts.32 So far, several focal therapies have been proposed and investigated for prostate cancer. In the past, the first phase I/II assessments of new focal ablation modalities have often been skipped and these methods were immediately used in clinical practice. The primary goals of this project are to determine the

safety and efficacy of IRE. The interest in QoL is increasingly important, and it is therefore of paramount importance to assess this aspect in addition to adverse events, pain and side effects. Furthermore, it is essential to select validated and recommended questionnaires, to be able to compare the focal therapy trial outcomes.13 An additional aspect of this study is the short-term evaluation of ‘salvage RP’, which is important, because some

patients will fail focal therapy and will need secondary radical resection of the prostate. This study protocol has some limitations. First, ablations of the posterior peripheral zone directly adjacent to the rectum have to be avoided in order to minimise possible rectal damage. Hydrodissection of the Denonvilliers’ space may be an option to be able to ablate closer to the capsule of this zone in case of later projects evaluating the role of IRE as focal treatment. Second, the maximum Brefeldin_A period between IRE and RP in this trial is 4 weeks. This limits analysis of the histopathology beyond this timeframe. It is clear that postponing the RP for evolving IRE effects is ethically not feasible. We will not use a customised mpMRI-based 3D-printed prostatectomy mold as described by Turkbey et al.22 Consequently, MRI slices and histopathology slides will not precisely match which will impede the exact comparison, resulting in a reduction of the correlation. Conclusion This trial will investigate the safety and efficacy of IRE in prostate cancer. Safety will be evaluated by reporting adverse events; side effects and QoL using validated questionnaires. Histopathology and radiological imaging will assess efficacy.