High-frequency irreversible electroporation versus transurethral resection of the prostate for benign prostatic hyperplasia (GIANT): a single-centre, randomised, double-blind, phase 3, non-inferiority trial

Background Transurethral resection of the prostate (TURP) is the gold standard for treating benign prostatic hyperplasia (BPH) but frequently causes retrograde ejaculation and bleeding. High-frequency irreversible electroporation (H-FIRE) is a non-thermal ablation technique offering tissue selectivity. We aimed to compare the efficacy and safety of H-FIRE versus TURP in men with symptomatic BPH. Methods In this investigator-initiated, single-centre, randomised, double-blind, non-inferiority trial at Shanghai East Hospital, China, men aged 40 years or older with symptomatic BPH (prostate volume 30–100 mL) were assigned (1:1) to undergo H-FIRE or TURP. To maintain blinding, a sham protocol involving perineal dressings and standardised irrigation was used. The co-primary outcomes were change from baseline in maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS) at 3 months. Non-inferiority margins were −4 mL/s for Qmax and 3 points for IPSS. Efficacy was analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT05306145. Findings Between June 30, 2022, and May 25, 2025, 118 participants were enrolled and randomly assigned to H-FIRE (n = 59) or TURP (n = 59). H-FIRE was non-inferior to TURP for both primary endpoints: mean Qmax improvement was 7.95 mL/s with H-FIRE versus 7.84 mL/s with TURP (adjusted difference 0.11 mL/s, 95% CI −2.52 to 2.73; p=0.001 for non-inferiority); mean IPSS reduction was −13.24 versus −13.75 (adjusted difference 0.50, −1.09 to 2.10; p=0.001 for non-inferiority). Retrograde ejaculation occurred in 0% (0/59) of patients in the H-FIRE group compared with 54.2% (32/59) in the TURP group (p < 0.0001). H-FIRE was associated with greater haemodynamic stability (mean haemoglobin change +0.82 g/L [95% CI −1.84 to 3.48] versus −12.14 g/L [−14.72 to −9.55]; p < 0.0001) but required longer postoperative catheterisation (median 19 days [IQR 15.0–22.0] versus 4 days [4.0–5.0]). There were no grade 3–4 adverse events, and no deaths occurred in either group. Interpretation At 3 months, H-FIRE provided short-term functional improvement non-inferior to TURP while completely preserving ejaculatory function and minimising blood loss. Although associated with longer temporary catheterisation due to tissue resorption, H-FIRE represents a viable function-sparing alternative for men prioritising sexual health and offers potential for ambulatory management. Funding National Natural Science Foundation of China (No. 82373048) and National Natural Science Foundation of China for Youth (No. 82303612).