By: Dan Sperling, MD

This is the last in a series of five articles on Irreversible Electroporation (IRE) for prostate cancer treatment.

With the growing interest in focal tumor ablation for prostate cancer, IRE has captured the interest of international clinical experts. In late December 2013, the scholarly journal Techniques in Vascular and Interventional Radiology published an article with the intriguing title, “Irreversible Electroporation: Ready for Prime Time?”[i] The authors write, “Emerging preclinical data as well as early clinical experience is showing promise for this technique in treating a variety of tumors including periportal liver masses, pancreatic cancer, perihilar renal tumors, prostate cancer, and other soft tissue tumors.” They caution, however, that IRE as a nonthermal ablation has yet to demonstrate safety and long term effectiveness against a high standard of research. In other words, if IRE is to be embraced in routine clinical practice, it must prove itself in randomized, prospective human trials. Four studies have been announced or begun as described below. 

1. NEAT Trial (Nanoknife Electroporation Ablation Trial). University College, London.

Twenty men with MRI-visible prostate cancer in the anterior of the prostate will be recruited and treated with focal IRE. The study’s purpose is to determine adverse events, genitourinary side effects, and early biopsy outcomes. Following focal ablation with IRE, patients will be followed for 12 months using standardized measures of urinary and sexual function. To examine disease control, at 6 months post-treatment each patient will undergo multiparametric MRI and targeted transperineal biopsy of the treated area.[ii]

2. A Pilot Study in Human Subjects Evaluating the Use of the NanoKnife System for Ablation of Prostate Cancer Tissue in a Low Risk Patient Population. Duke University, Durham NC

Although this is to be a small study (6 patients enrolled), it is similar to the University College study in its purpose. Patients with unifocal disease will be treated with IRE. The safety of the procedure will be determined by the occurrence of any adverse events, and the impact on urinary and sexual function. Short-term efficacy will be assessed by a transperineal 3-Dimensional Prostate Biopsy (3D-PMB) on the side of the gland treated at three months after treatment. To qualify patients previously diagnosed with low risk disease, prior to enrollment each patient will undergo 3D-PMB to identify a unifocal tumor which will be targeted for IRE treatment. After the 3 month post-treatment biopsy, all data will be submitted to the FDA for evaluation of short term safety and effectiveness. Subjects will continue to be followed for two years from treatment.[iii]

3. Safety and Efficacy of Irreversible Electroporation in Ablation of Prostate Cancer in Humans. Clinical Research Office of the Endourological Society (CROES)/AMC University Hospital, Netherlands.

This study is designed differently from the first two in that up to 16 enrolled men with low or intermediate risk prostate cancer who are already scheduled for prostatectomy will be treated with IRE about a month before surgery. The zone of treatment will be identified during an image-based planning stage using MRI and contrast enhanced ultrasound (CEUS) of the prostate. After IRE, safety data will be collected and patients followed at 1 week, 2 weeks, shortly before and after prostatectomy, and 1 week after surgery. Specifically, patients will again be imaged with MRI and CEUS shortly before prostatectomy to examine the zone of IRE ablation. The readings of the images will be compared with the ablation results demonstrated in the actual prostate specimens after surgery. Again, both safety and efficacy of IRE ablation will be evaluated, including standardized questionnaires of erectile function and patient satisfaction.[iv]

4. Multicenter Randomized Two-Arm Intervention Study Evaluating Irreversible Electroporation for the Ablation of Localized Unilateral Prostate Cancer. Clinical Research Office of the Endourological Society (CROES)/6 European centers.[v]

The most scientifically rigorous human study of IRE yet designed, this prospective randomized clinical trial has been announced by W. van den Bos, B.G. Muller, and J.J.C.M.H. de la Rosette. The proposed number of enrolled subjects (200) and the 5-year follow-up constitute a high level of scientific research. Subjects with predetermined unifocal prostate cancer will be randomized into two groups: one group will have the entire gland ablated using IRE, and the other group will have the half of the gland containing the cancer ablated using IRE. Subjects will be followed for safety and efficacy. Interested readers can access the published proposal, including the rationale for focal therapy, at http://www.croesoffice.org/portals/0/march2013vdbos.pdf.

While the first three studies will generate published results much sooner than the last, it is the high standard of clinical research that distinguishes the research proposed by Van den Bos, et al. The use of IRE in the prostate and other organs will continue to be available in a small number of U.S. centers during the research period, but the results of all four studies will be eagerly awaited. If IRE can be shown to fulfill its current promise as a therapy that selectively and effectively destroys cancer cells while sparing nearby structures, it will be a welcome addition to the field of prostate cancer treatment.

[i] Lu DS, Kee ST, Lee EW. Irreversible electroporation: ready for prime time? Tech Vasc Interv Radiol. 2013 Dec;16(4):277-86.

[ii] Valerio M, Dickinson L, Ali A, Ramachadran N et al. A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial

(NEAT).Contemp Clin Trials. 2014 Jul 26. Doi: 10.1016/j.cct.2014.07.006. [Epub ahead of print]

[iii] http://clinicaltrials.gov/ct2/show/NCT01972867?term=irreversible+electroporation+prostate&rank=4

[iv] http://clinicaltrials.gov/ct2/show/NCT01790451?term=irreversible+electroporation+prostate&rank=1

[v] Van den Bos W, Muller BG & de la Rosette JJ. A randomized controlled trial on focal therapy for localized prostate carcinoma: hemiblation versus complete abltion with irreversible electroporation. J Endourol. 2013 Mar;27(3):262-4.