Focal therapy for prostate cancer (PCa) is a hybrid approach utilising ablative treatment of the involved prostate gland and continued active surveillance of the unaffected gland. Numerous energy sources exist, including irreversible electroporation (IRE). Focal IRE appears to be a safe, feasible treatment option in carefully selected patient cohorts. However, despite its increasing uptake, robust evidence to support its efficacy and optimal utilisation is still maturing. Furthermore, focal IRE is not currently offered at any public hospital in Australia; the FIREFLY registry will be the first of its kind.

This is a prospective, single-centre, clinical research registry. Primary objectives: 1. Determine the rate of 18 to 36-month local disease control 2. Determine the rate of 5-year biochemical progression-free survival. Secondary objectives: 1. Measure the change in clinician-reported quality of life 2. Measure the change in patient-reported generic and disease-specific quality of life 3. Determine the rate of salvage treatment. Men are deemed eligible if they have: an age of 40-85 years, life expectancy >10 years, prostate-specific antigen (PSA) <15 ng/ml, clinical stage T1c or T2a, Prostate Imaging-Reporting and Data System (PIRADS) score of 3-5 or suspicious prostate lesion on prostate-specific membrane antigen positron emission tomography (PSMA-PET), imaging-concordant International Society of Urological Pathology (ISUP) 1 (≥10mm in ≥1 core) or ISUP 2 (any length) or ISUP 3 (longest core <10mm) prostate adenocarcinoma, and template biopsies of the remaining gland showing either no cancer or clinically insignificant PCa (<10mm ISUP 1). All patients will undergo initial multiparametric MRI (mpMRI) or PSMA-PET, followed by targeted and template transperineal prostate biopsy. They will also complete baseline quality-of-life questionaries in the form of FACT-G7, IPSS, IIEF-5, and EPIC bowel domain. Oncological outcomes will be assessed by performing PSA testing at six weeks, followed by three-monthly. Repeat mpMRI and/or PSMA PET will be performed per-protocol 18 months post-treatment, or earlier if clinically indicated. Functional outcomes will be assessed by performing CTCAE and quality-of-life questionnaires at six weeks, followed by six-monthly.

Institutional ethics approval has been received. Patient recruitment has opened in March 2025, with a planned recruitment target of 100 patients. Statistical analyses will include: comparisons between patients with pathological progression and control, multivariable logistic regression analysis to identify predictors of pathological progression, and Kaplan-Meier analyses to evaluate freedom from pathological progression and salvage treatment.

The FIREFLY registry is the first exploring focal IRE treatment in an Australian public hospital setting. It aims to contribute to the growing body of international analyses on the feasibility/safety of focal IRE treatment and its oncological/functional outcomes.