Research Article: Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments

Date Published: April 15, 2019

Publisher: Public Library of Science

Author(s): E. Guenther, N. Klein, S. Zapf, S. Weil, C. Schlosser, B. Rubinsky, M. K. Stehling, Aamir Ahmad.

http://doi.org/10.1371/journal.pone.0215093

Abstract

Irreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time.

The patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8–16.93) for Gleason 6, 14.6% (CI95: 8.8–23.7) for Gleason 7 and 39.5% (CI95: 23.5–61.4) for Gleason 8–10.

The results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore.

Partial Text

The incidence of prostate cancer (PCa) is increasing worldwide, with an estimated 1.1 million new cases in 2012 [1]. Established PCa-treatments like radical prostatectomy (RPE) or radiation therapy (RT) aim to treat the whole prostate, which is associated with side effects such as impotence, incontinence and potential damage to the rectum and bladder [2][3], whilst at best providing only moderate survival benefits compared to active surveillance [4]. It has recently been shown that the largest PCa lesion with the highest tumor grade predominantly influences the progression of disease [5][6], suggesting that treatment of this index lesion alone would be highly effective [7][8]. Focal thermal therapies such as Cryosurgery, Radiofrequency Ablation (RFA) or High Intensity Focal Ultrasound (HIFU) have gained ground as minimally invasive alternatives to established therapies [9][10]. In comparison, Irreversible Electroporation (IRE), a novel tissue ablation technology, has the advantage of being non-thermal with elements of tissue selectivity [11], which significantly reduces toxicity on vital anatomical structures surrounding the malignancy. Because of these properties, IRE might become a standard therapy for PCa, and further, a problem solver for advanced T4-cancers for which there are few other treatment options and/or only treatable with resulting permanent damage.

This retrospective analysis of 471 treatments of PCa with IRE, comprising all clinical stages and recurrent disease, with over 6-year follow-up, to our knowledge constitutes as the largest patient cohort with the longest observation time. Our data appears coherent with the data previously published but extends to higher grades and stages confirming that IRE is an effective minimally-invasive procedure for the treatment of PCa.

The retrospective evaluation of our data allows the conclusion that Irreversible Electroporation (IRE) is a safe, effective and suitable modality for the treatment of PCa at all clinical stages and recurrent disease. Treatment fields included the lower urinary sphincter, seminal vesicles, neurovascular bundles and in some cases partially the rectum and bladder, yet overall toxicity was low. Continence was preserved in all cases. In terms of local tumor control the comparison of IRE with radical prostatectomy (RPE) revealed similar recurrence rates over time, suggesting similar effectiveness of IRE to RPE. Thus the data illustrates the feasibility of IRE for PCa treatments, with similar functional outcomes and short to midterm efficacy to RPE, but much lower toxicity profile. Before IRE has the potential to become a new standard of care for the treatment of PCa, the presented data needs to be confirmed by more systematic studies. A more stringent evaluation is of course required, of which the multi-center registry (NCT02255890) is a first step, as well as optimization and standardization of diagnostic work-up, patient selection, the technical procedure of IRE and follow-up regime.

 

Source:

http://doi.org/10.1371/journal.pone.0215093

 

Leave a Reply

Your email address will not be published.