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Article of the Week: Focal irreversible electroporation as primary treatment for localized prostate cancer

Every Week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Focal irreversible electroporation as primary treatment for localized prostate cancer

 

Willemien van den Bos*†‡, Matthijs J. Scheltema*†‡, Amila R. Siriwardana*Anton M.F. Kalsbeek*, James E. Thompson, Francis Ting*, Maret Bohm*,
Anne-Maree Haynes*, Ron Shnier§, Warick Delprado¶ and Phillip D. Stricker

 

*Garvan Institute of Medical Research and Kinghorn Cancer Centre, St Vincents Prostate Cancer Centre, Darlinghurst, NSW, Australia, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, §Southern Radiology, Randwick, and Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia

 

Abstract

Objectives

To determine the safety, quality of life (QoL) and short‐term oncological outcomes of primary focal irreversible electroporation (IRE) for the treatment of localized prostate cancer (PCa), and to identify potential risk factors for oncological failure.

Patients and Methods

Patients who met the consensus guidelines on patient criteria and selection methods for primary focal therapy were eligible for analysis. Focal IRE was performed for organ‐confined clinically significant PCa, defined as high‐volume disease with Gleason sum score 6 (International Society of Urological Pathology [ISUP] grade 1) or any Gleason sum score of 7 (ISUP grades 2–3). Oncological, adverse event (AE) and QoL outcome data, with a minimum of 6 months’ follow‐up, were analysed. Patient characteristics and peri‐operative treatment variables were compared between patients with and without oncological failure on follow‐up biopsy. Wilcoxon’s signed rank test, Wilcoxon’s rank sum test and the chi‐squared test were used to assess statistically significant differences in paired continuous, unpaired continuous and categorical variables respectively.

Results

A total of 63 patients met all eligibility criteria and were included in the final analysis. No high‐grade AEs occurred. QoL questionnaire analysis demonstrated no significant change from baseline in physical (P = 0.81), mental (P = 0.48), bowel (P = 0.25) or urinary QoL domains (P = 0.41 and P = 0.25), but there was a mild decrease in the sexual QoL domain (median score 66 at baseline vs 54 at 6 months; P < 0.001). Compared with baseline, a decline of 70% in prostate‐specific antigen level (1.8 ng/mL, interquartile range 0.96–4.8 ng/mL) was seen at 6–12 months. A narrow safety margin (P = 0.047) and system errors (P = 0.010) were identified as potential early risk factors for in‐field oncological failure. In‐field and whole‐gland oncological control on follow‐up biopsies was 84% (38/45 patients) and 76% (34/45 patients); this increased to 97% (38/39 patients) and 87% (34/39 patients) when patients treated with a narrow safety margin and system errors were excluded.

Conclusion

Our data support the safety and feasibility of focal IRE as a primary treatment for localized PCa with effective short‐term oncological control in carefully selected men.

Editorial: Has tailored, tissue‐selective tumour ablation in men with prostate cancer come of age?

There are two principal challenges that face the growing number of clinical investigators that are evaluating tissue‐preserving therapies in men with prostate cancer.

The first is that every man’s prostate is different. So different and so unique are the personal attributes of a man’s prostate that it would, just like the iris or fingerprint, qualify as a unique identifier. It is just a few practical considerations that prevent it from doing so. This is a challenge that the clinician treating the liver, kidney or brain does not face – as these organs do not exhibit the between patient variability that we see in the prostate.

The second relates to within‐patient (or within‐prostate) differences. The nature of the tissue being treated will depend on which part of the prostate is being treated – peripheral, transition or central zone. Each of these zones will, in turn, be dependent on the age of the prostate, the extent of BPH, exhibit calcification and or cysts, and may or may not be infiltrated by acute and/or chronic inflammation.

These two sets of variability present considerable challenges to investigators that seek to selectively ablate a given zone of tissue, given that the nature of the target volume will be different in every man treated and exist in a context that is specific to the that man.

Add to this challenge the variability in prostate cancer tumour attributes – volume, location, heterogeneity (genetic, radiological, and histological), degree of immune infiltrate, and the extent of microscopic extension, we begin to get the picture 1.

The paper in this issue of the BJUI by van den Bos et al. 2 describes a modern attempt to overcome these challenges and attempt and achieve personalised care to individuals, their prostate glands, and their cancer.

The team used irreversible electroporation (IRE) to create a selective ablation zone around a given tumour volume, embracing a margin of 5–10 mm. This method of ablation has certain attributes that lend itself to the task. It can be applied to any zone of the prostate. It is not limited by the size of the prostate. It can create lesions of variable volume. The treatment is quick and therefore not overly affected by prostate gland swelling. Because the treatment uses an interstitial approach (needle based) the effectors of the treatment move with the prostate during respiration and changes in rectal fullness. These attributes mitigate most of the challenges generated by between‐patient variability.

The authors describe the methods by which they manage tumour‐specific differences. These important but rather technical constraints (to the non‐expert) comprise: tumour‐volume dependent variable needle load; individualised tissue impedance‐based energy adjustment; minimising variability in needle–needle distance; application of a 10‐mm margin; and near term verification of tissue change with post‐treatment MRI.

These conditions seem to have paid off. Although every patient underwent a treatment that was bespoke to both their prostate and their prostate cancer, the results were most promising for this truly personalised sub‐specialty of uro‐oncology.

The treatment was safe. There were no high‐grade adverse events reported in the 63 men included in the analysis. The disease‐specific and generic quality of life was not compromised by the range of interventions administered except in relation to the sexual quality of life domain that was marginally affected – a median score of 66 prior to therapy diminished to 54 when measured again 6‐months after treatment.

The authors managed to get a high proportion of men to undergo verification biopsy after treatment. From this they derived two oncological outcomes. These comprised freedom from clinically significant prostate cancer (high‐volume exclusive Gleason pattern 3 and/or any Gleason pattern 4 or 5) within and on the edge of field on the one hand and out of field on the other.

In patients who were free of any technical failure in relation to the administration of IRE and had a 10‐mm margin incorporated, the results were very promising with most of the patients evaluated free of disease both within (97% [38/39 men]) and out of field (87% [34/39 men]).

Although the numbers of patients reported upon are relatively small, the overall results represent a welcome improvement on previously published phase I clinical trial data using IRE, probably as a result of better patient selection and optimisation of energy delivery 3. The results, however, are reassuringly similar to previous case‐series that used alternative energy sources but were predicated on an anatomical‐based approach to tissue preservation 4. The tumour‐based approach reported upon by van den Bos et al. 2 is much more challenging as it exposes any subtle deficiencies in the base‐line risk‐stratification and imposes exacting constraints on the reliability of the energy source in creating irreversible cell kill where cell kill is intended.

Mark Emberton
Division of Surgery and Interventional Science, UCL, London, UK

 

References
  • Linch M, Goh G, Hiley C et al. Intratumoural evolutionary landscape of high‐risk prostate cancer: the PROGENY study of genomic and immune parametersAnn Oncol201728: 2472–80

 

  • van den Bos W, Scheltema MJ, Siriwardana AR et al. Focal irreversible electroporation as primary treatment for localized prostate cancerBJU Int 2018121: 716–24

 

  • Valerio M, Dickinson L, Ali A et al. Nanoknife electroporation ablation trial: a prospective development study investigating focal irreversible electroporation for localized prostate cancerJ Urol 2017197: 647–54

 

  • Ahmed HU, Hindley RG, Dickinson L et al. Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development studyLancet Oncol 201213: 622–32

 

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