First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer.

Abstract

Irreversible electroporation, as a nonthermal therapy of prostate cancer, has been used in clinic for several years. The mechanism of irreversible electroporation ablation is thermal independent; thus, the main structures (eg, rectum, urethra, and neurovascular bundle) in prostate are spared during the treatment, which leads to the retention of prostate function. However, various clinical trials have shown that muscle contractions occur during this therapy, which warrants deep muscle anesthesia. Use of high-frequency bipolar pulses has been proposed to reduce muscle contractions during treatment, which has already triggered a multitude of studies at the cellular and animal scale. In this study, we first investigated the efficacy and safety of high-frequency bipolar pulses in human prostate cancer ablation. There are 40 male patients with prostate cancer aged between 51 and 85 years involved in this study. All patients received 250 high-frequency bipolar pulse bursts with the repeat frequency of 1 Hz. Each burst comprised 20 individual pulses of 5 microseconds, so one burst total energized time was 100 microseconds. The number of the electrodes ranged 2 to 6, depending on tumor size. A small amount of muscle relaxant was still needed, so there were no visible muscle contractions during the pulse delivery process. Four weeks after treatment, it was found that the ablation margins were distinct in magnetic resonance imaging scans, and the prostate capsule and urethra were retained. Eight patients underwent radical prostatectomy for pathological analysis after treatment, and the results of hematoxylin and eosin staining revealed that the urethra and major vasculature in prostate have been preserved. By overlaying the electric field contour on the ablation zone, the electric field lethality threshold is determined to be 522 ± 74 V/cm. This study is the first to validate the feasibility of tumor ablation by high-frequency bipolar pulses and provide valuable experience of irreversible electroporation in clinical applications.