FOCAL THERAPY Focal Irreversible Electroporation for Prostate Cancer
By: Sean Ong, MBBS, Epworth Healthcare, Melbourne, Australia; Jianliang Liu, MBBS, Epworth Healthcare, Melbourne, Australia, The Royal Melbourne Hospital, University of Melbourne, Australia; Nathan Lawrentschuk, MBBS, FRACS, PhD, Epworth Healthcare, Melbourne, Australia, The Royal Melbourne Hospital, University of Melbourne, Australia | Posted on: 09 Jun 2023
Irreversible electroporation (IRE) is an emerging form of focal therapy that utilizes pulses of electricity to ablate prostate cancer cells. At a microscopic level, the pulses of electricity create nanopores in the cell membranes, which then initiate apoptosis and permanent cell death.1 IRE does not rely on thermal change for ablation, therefore avoiding the heat-sink effect.2 Studies have demonstrated that structures such as large blood vessels and nerves are spared within the ablation zone.3,4 Therefore, IRE has the potential to provide good oncologic control while minimizing adverse effects such as urinary incontinence and erectile dysfunction for prostate cancer patients.5 Early results are promising; however, more data are needed to fully understand its efficacy and optimize its use.
The procedure is performed under a general anesthetic with the patient in the lithotomy position. Nineteen-gauge needles are placed transperineally into the prostate through a biopsy grid to surround the cancer with an adequate margin. Machine software calculates the voltages required to achieve optimal ablation parameters; this is refined by the urologist. Pulses of electricity are then administered between these probes, during which caution is taken not to exceed the thermal threshold. The probes are then removed, and an indwelling catheter inserted. Patients go home on the day of the procedure, and the catheter is removed 3-5 days postoperatively.
Focal IRE is used at the moment in 2 settings: for newly diagnosed and radio-recurrent prostate cancer.6 To the best of our knowledge, there are 8 existing cohort studies to date exploring IRE in newly diagnosed prostate cancer, and the results are summarized in the Table. The 2 largest studies, by Blazevski et al7 (n=123) and Yaxley et al8 (n=70) found a 9.8% and 10% in-field recurrence, respectively, and 12.7% and 27.5% out-of-field recurrence rate, respectively, at 12 months of follow-up. The FIRE trial is the only published data on IRE in the radio-recurrent setting to our knowledge.9 Their results found a 6% in-field recurrence and 18% out-of-field recurrence rate at 12 months. Six men were found to have metastatic disease.
Table. Summary of Existing Studies Evaluating Oncologic Outcomes, Functional Outcomes, and Complications of Irreversible Electroporation on Prostate Cancer
|Authors, y||No.||Patient demographics||In-field/out-of-field recurrence||No. men who progressed to whole-gland therapy||Functional outcomes||Complications|
|Blazevski et al, 202011||50||Median PSA 6.25 (IQR 4.35-8.9)
3+3: 5 patients
3+4: 37 patients
4+3: 6 patients
4+4: 2 patients
|In-field recurrence: 1 patient
Out-of-field recurrence: 8 patients
38/40 continent (95%), 30/32 potent (94%)
10 grade 1 (20%),
9 grade 2 (18%)
|Blazevski et al, 20207||123||Median PSA 5.725 (IQR 3.8-8.0)
3+3: 12 patients
3+4: 88 patients
4+3: 23 patients
|In-field recurrence: 10 patient
Out-of-field recurrence: 13 patients
80/81 continent (98.8%), 49/53 potent (93%)
27 grade 1 (22%),
11 grade 2 (9%)
|Collettini et al, 201912||30||Median PSA 8.65 (IQR 5-11)
3+3: 7 patients
3+4: 23 patients
|In-field recurrence: 5 patients
Out-of-field recurrence: 2 patients
28/29 continent (96.5%), 23/29 potent (79.3%)
2 intermittent hematuria grade 1 (6.7%), 3 UTI grade 2 (10%), 1 urethral stricture requiring surgery grade 3 (2%)
|Scheltema et al, 201713||18||Median PSA 3.5 (IQR 3.2-8.4)
3+3: 0 patients
3+4: 6 patients
4+3: 5 patients
4+4: 2 patients
≥4+5: 5 patients
|In-field recurrence: 1 patient
Out-of-field recurrence: 1 patient
8/8 continent (100%), 2/4 potent (50%)
5/18 grade 1, 2/18 grade 2
|Ting et al, 201614||25
|Median PSA 6.0 (IQR 4.3-8.6)
3+3: 2 patients
3+4: 15 patients
4+3: 8 patients
|In-field recurrence: 0 patients
Out-of-field recurrence: 5 patients
0% change from baseline for continence and potency
5 urinary retention grade 1 (20%), 6 intermittent hematuria (24%),
1 nSTEMI grade 3
|Van den Bos et al, 201815||63||Median PSA 6.0 (IQR 3.2-8.4)
3+3: 9 patients
3+4: 38 patients
4+3: 16 patients
|In-field recurrence: 7 patients
Out-of-field recurrence: 4 patients
|Not reported||12 Mo:
45/45 continent (100%), 10/13 potent (77%)
15 hematuria, dysuria, urgency grade 1 (24%);
7 UTI, incontinence grade 2 (11%)
|Yaxley et al, 20228||70||Median PSA 6.1
ISUP 1: 5 patients
ISUP 2: 35 patients
ISUP 3: 17 patients
ISUP 4: 6
ISUP 5: 7
|In-field recurrence, significant prostate cancer: 7 patients
In-field recurrence, insignificant prostate cancer: 3 patients
Out-of-field recurrence, significant prostate cancer: 6 patients
Out-of-field recurrence, insignificant prostate cancer: 18 patients
25/29 potent (85.7%), 68/70 continent (97.1%)
|No complications over Clavien-Dindo classification grade 2|
|Shin et al, 202216||17||Median PSA 7.5 ng/mL
ISUP 1: 11 patients
ISUP 2: 2 patients
ISUP 3: 4 patients
|In-field recurrence: 1 patient (5.9%)
Out-of-field recurrence: 1 patient (5.9%)
|1||Not mentioned||Clavien-Dindo classification:
10 grade 1 (59%),
2 grade 2 (12%)
|Blazevski et al, 20229||37||Median PSA 3.5
Previous brachytherapy: 26 patients (70%)
Previous EBRT 11 patients (30%)
ISUP 2: 15 patients
ISUP 3: 2 patients
ISUP 4: 7 patients
ISUP 5: 5 patients
|17 Patients had post-treatment biopsy
In-field significant recurrence: 1 patient (6%)
Out-of-field recurrence: 3 patients (18%)
|Local recurrence only: 4 patients
(RARP 1, ADT 2, surveillance 1)
Metastatic recurrence: 6 patients (ADT 6)
25/27 continent (93%), 4/27 potent enough for intercourse (15%)
7 grade 1/2 (19%), 7 grade 3 (19%)
|Abbreviations: ADT, androgen deprivation therapy; CTCAE, Common Terminology Criteria for Adverse Events; EBRT, external beam radiation therapy; IQR, interquartile range; ISUP, International Society of Urological Pathology; nSTEMI, non-ST-elevation myocardial infarction; PSA, prostate-specific antigen; RARP, robotic-assisted radical prostatectomy; UTI, urinary tract infection.|
Overall, the functional outcomes post-focal IRE are good compared to radical treatment. Potency rates in the newly diagnosed cohorts range from 85%-95%, and continence rates range from 88%-100%. Not surprisingly, in the radio-recurrent setting, the FIRE trial reported a 15% rate of potency and 93% continence. Clinically significant complications (ie, Clavien-Dindo classification 3 or greater) only occurred in radio-recurrent patients. There has been 1 case report of a rectoprostatic fistula.10
In summary, the literature shows that IRE is a safe procedure which can achieve good short-term oncologic control and low side-effect rates. Patient selection remains the key to improving outcomes, in particular decreasing rates of out-of-field recurrence overall and metastases rates in the radio-recurrent patients. New imaging modalities such as prostate-specific membrane antigen positron emission tomography-CT may help in this regard. Future studies need to incorporate larger cohort sizes and longer follow-up. Most importantly, consensus for study outcomes and follow-up across all focal therapy modalities needs to be reached in order to progress these new technologies closer toward routine clinical management.
- Faroja M, Ahmed M, Appelbaum L, et al. Irreversible electroporation ablation: is all the damage nonthermal?. Radiology. 2013;266(2):462-470.
- Yu NC, Raman SS, Kim YJ, Lassman C, Chang X, Lu DS. Microwave liver ablation: influence of hepatic vein size on heat-sink effect in a porcine model. J Vasc Interv Radiol. 2008;19(7):1087-1092.
- Li W, Fan Q, Ji Z, Qiu X, Li Z. The effects of irreversible electroporation (IRE) on nerves. PLoS One. 2011;6(4):e18831.
- Maor E, Ivorra A, Leor J, Rubinsky B. The effect of irreversible electroporation on blood vessels. Technol Cancer Res Treat. 2007;6(4):307-312.
- Valerio M, Dickinson L, Ali A, et al. Nanoknife electroporation ablation trial: a prospective development study investigating focal irreversible electroporation for localized prostate cancer. J Urol. 2017;197(3 Part 1):647-654.
- Ong S, Chen K, Grummet J, et al. Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?. BJU Int. 2023;131(1):20-31.
- Blazevski A, Scheltema MJ, Yuen B, et al. Oncological and quality-of-life outcomes following focal irreversible electroporation as primary treatment for localised prostate cancer: a biopsy-monitored prospective cohort. Eur Urol Oncol. 2020;3(3):283-290.
- Yaxley WJ, Gianduzzo T, Kua B, Oxford R, Yaxley JW. Focal therapy for prostate cancer with irreversible electroporation: oncological and functional results of a single institution study. Investig Clin Urol. 2022;63(3):285-293.
- Blazevski A, Geboers B, Scheltema MJ, et al. Salvage irreversible electroporation for radio-recurrent prostate cancer—the prospective FIRE trial. BJU Int. 2022;10.1111/bju.15947.
- Ong S, Alhamdani Z, Lawrentschuk N. Rectourethral fistula following focal irreversible electroporation for prostate cancer. BMJ Case Rep. 2022;15(9):e249816.
- Blazevski A, Amin A, Scheltema MJ, et al. Focal ablation of apical prostate cancer lesions with irreversible electroporation (IRE). World J Urol. 2021;39(4):1107-1114.
- Collettini F, Enders J, Stephan C, et al. Image-guided irreversible electroporation of localized prostate cancer: functional and oncologic outcomes. Radiology. 2019;292(1):250-257.
- Scheltema MJ, van den Bos W, Siriwardana AR, et al. Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer. BJU Int. 2017;120(Suppl 3):51-58.
- Ting F, Tran M, Böhm M, et al. Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control. Prostate Cancer Prostatic Dis. 2016;19(1):46-52.
- van den Bos W, Scheltema MJ, Siriwardana AR, et al. Focal irreversible electroporation as primary treatment for localized prostate cancer. BJU Int. 2018;121(5):716-724.
- Shin D, Yoon CE, Kwon HJ, et al. Irreversible electroporation for prostate cancer using PSMA PET-CT. Prostate Int. 2023;11(1):40-45.