Irreversible Electroporation of Prostate Cancer an Update

Research Article

Irreversible Electroporation of Prostate Cancer an Update

  • Anthony Kodzo-Grey Venyo *

*Corresponding Author: Anthony Kodzo-Grey Venyo, North Manchester General Hospital, Department of Urology, Delaunays Road, Manchester, M8 5RB, United Kingdom.

Citation: Anthony Kodzo-Grey Venyo., (2024), Irreversible Electroporation of Prostate Cancer an Update., Journal of Clinical Surgery and Research., 5(9); DOI:10.31579/2768-2757/152

Copyright: © 2024, Anthony Kodzo-Grey Venyo., This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 11 November 2024 | Accepted: 20 November 2024 | Published: 20 December 2024

Keywords: adenocarcinoma of prostate gland; prostate biopsy; ultrasound scan; computed tomography scan; magnetic resonance imaging scan; good oncology outcomes; further studies

Abstract

It has been known that the undertaking of radical treatment for localized prostate cancer has often been ensued by a major impact upon the quality of life of individuals who had undergone radical treatment for their localized prostate cancer, some of which include urinary incontinence and other types of voiding problems as well as erectile dysfunction. This has led to the development of focal therapy for prostate cancer, which has the objective of attaining equivalent oncology control of the problem, whilst improving upon episodes of voiding and incontinence problems as well as maintaining coital and erectile function preservation of each individual patient. Irreversible electroporation (IRE) is a new treatment option which utilises using pulsed high-voltage low-energy direct electric current for the ablation of tumour. As a non-thermal energy platform, IRE does have the advantage of sparing the peri-prostatic encompassing functional structures, including blood vessels and connective tissue. Histopathology examination outcomes pursuant to the undertaking of IRE to prostate cancer had demonstrated sharp demarcation between the ablated and non-ablated tissue, whereas thermal ablation techniques had demonstrated a transitional zone of partially damaged tissue due to insufficient temperatures for definitive ablation. An internation multi-centre study pursuant to the treatment 411 patients who had undergone treatment for prostate cancer from July 2015 up to April 2020 had concluded that: 

  • For men who are afflicted by localized prostate cancer, IRE could achieve good urinary and sexual function outcomes and a reasonable oncology result. 
  • The real-world data are consistent with earlier studies, including recently published randomized controlled studies. 
  • The long-term oncology results need further investigation and follow-up.
  • The rate of AEs was 1.8% at 3 months after IRE and major AEs were rare.
  • The IPSS initially had worsened but had returned to baseline level at 6 months. 
  • The IIEF-5 had worsened at 3 months and then had been maintained stable subsequently. 
  • IRE had been able to achieve a reasonable oncology outcome. 
  • The clinically significant prostate cancer rate in the repeat biopsy during 12–18 months was in 24.1%. 
  • The long-term oncology results need further investigation and follow-up. 
  • The real-world data are consistent with earlier studies including recently published randomized controlled studies.

Introduction

It has been iterated that prostate cancer represents the second most common solid tumour that afflicts men with an incidence which was 1,414,259 new cases globally in the year 2020.[1] [2] It has been pointed out that the standard of care for localized prostate cancer, depending upon the International Society of Urological Pathology (ISUP) grade and the stage of the disease, had traditionally been active surveillance, radical prostatectomy (RP), and radiotherapy (RT). RP and RT had been documented to be the long-standing curative whole-gland approaches which had been associated with the best possible oncology outcomes for patients who are afflicted by localized prostate cancer. Nevertheless, it has also been pointed out that these curative treatment options have tended to be associated with adverse quality-of-life outcomes such as urinary incontinence and sexual dysfunction. In view of this, newer advances in the field of prostate cancer management had been directed towards the provision of focal therapy with an intent of balancing the patient’s quality of life while treating the lesion effectively.

It has been pointed out that focal ablation therapy could cover a wide range of ablation treatment options depending upon the site of location of the tumour within the prostate gland. [1] It has been iterated that the most common ablative treatment options which tend to be used are focal, quadrant, hemi-ablation, and hockey-stick ablation. [1] [3] Focal therapies such as irreversible electroporation (IRE), high-intensity focused ultrasound (HIFU), cryoablation, radiofrequency ablation (RFA), photodynamic therapy (PDT), brachytherapy, and focal laser ablation (FLA) had been developed with the objective to preserve the non-cancerous prostatic tissue as well as to reduce the harm to the neurovascular bundles, urethra, urethral sphincter, and the rectum which could happen.[1] [4] It has been pointed out that cryotherapy, FLA, RFA, and PDT do administer localized thermal ablation but could also cause nonselective injury to the tissues that encompass the targeted area, as they do lack precision when they are compared to the IRE. [1] It has furthermore, been iterated that focal treatment options which rely upon thermal ablation are also affected by the heat sink effect, when the area of ablation is too close to the blood vessels.[1] [5] It has in addition been pointed out that IRE is a relatively new focal therapy when compared to HIFU or cryoablation, which had been explored more extensively. When a cell is subjected to an electric field, a process called electroporation does develop, wherein nanopores are formed upon the cell membrane. IRE is documented to use repetitive electric pulses in order to create nanopores upon the cell membrane and which induces cell death due to membrane instability and disruption of the cellular homeostasis. [1] [6]

Considering that utilization of irreversible electroporation in the treatment of localised prostate cancer has only been undertaken in a few well-resourced centres in the world, it would be envisaged that the majority of practising clinicians in every part of the world including: general practitioners, urologists, oncologists, pathologists, as well as radiologists would not be familiar with the utilization of irreversible electroporation in the treatment of localised prostate cancer. The ensuing article on irreversible electroporation of carcinoma of the prostate gland is divided into two parts:(A) Overview, and (B) miscellaneous narrations and discussions from some case reports, case series, and studies related to irreversible electroporation of prostate cancer. 

Aim

To provide an update on irreversible electroporation of prostate cancer 

Methods

Internet data bases were searched including: Google, google scholar; yahoo; and PUBMED. The search words that were used included: Irreversible electroporation of prostate cancer; prostatic cancer irreversible electroporation; Irreversible electroporation of the prostate gland. Fifty-six (56) references were identified which were used to write the article which has been divided into two parts: (A) Overview, and (B) miscellaneous narrations and discussions from some case reports, case series, and studies related to irreversible electroporation of prostate cancer.

Results

[A] Overview 

Definition / general statements [7]

  • It has been iterated that even though there are various types of cancer that afflicts the prostate gland, adenocarcinoma of the prostate gland is the most common malignancy of the prostate gland
  • It has been pointed out that adenocarcinoma of the prostate gland does originates from prostatic secretory epithelium
  • Essential features
  • The essential manifesting features of adenocarcinoma of the prostate gland had been summated as follows: [7]
  • It has been pointed out that the clinical and radiology-image features of the prostate gland, are neither sensitive nor specific to be used to establish the diagnosis of adenocarcinoma of the prostate gland 
  • It has been explained that diagnosis of adenocarcinoma of the prostate gland is often established based upon pathology examination of specimens of the prostate gland which had been obtained by non-targeted needle biopsies during the investigation of raised serum prostate specific antigen (PSA) of the patient
  • It has been pointed out that during pathology examination of specimens of the prostate gland, absence of basal cell layer in the specimen of the prostate gland is a pathognomonic histological feature
  • It has been iterated that the pathognomonic diagnostic features of adenocarcinoma of the prostate gland include the ensuing: circumferential perineural invasion, glomerulations and collagenous micronodules (mucinous fibroplasia)
  • It has been pointed out that other histopathology examination features of adenocarcinoma of the prostate gland include the ensuing: infiltrative architecture, nucleolar prominence, amphophilic cytoplasm and some intraluminal contents (crystalloids, blue mucin, pink amorphous material)
  • Terminology
  • It has been iterated that: Other terminologies, had tended to be utilized for adenocarcinoma of the prostate generally as follows: [7]
  • Prostate cancer
  • Prostate adenocarcinoma
  • It has been iterated that: Various sub-types of adenocarcinomas of the prostate gland exist including: 
  • Acinar adenocarcinoma
  • Ductal adenocarcinoma
  • Atrophic adenocarcinoma
  • Pseudo-hyperplastic adenocarcinoma
  • Microcystic adenocarcinoma
  • Foamy gland adenocarcinoma
  • Mucinous adenocarcinoma
  • Signet ring variant of adenocarcinoma
  • Pleomorphic giant cell adenocarcinoma
  • Sarcomatoid adenocarcinoma

Epidemiology

The epidemiology of adenocarcinoma of the prostate gland has been summated as follows: [7]

  • It has been documented that adenocarcinoma of the prostate gland, is the second most common cancer and second leading cause of cancer related death in American men. [8] 
  • It has been iterated that in 2024, about 2.0 million people would be diagnosed with cancer within the United States of America (U.S.A.) An estimated 310,720 women and 2,790 men would be diagnosed with breast cancer, which makes it the most common cancer diagnosis. Prostate cancer is the leading cancer diagnosis among men and the second most common diagnosis overall with 299,010 expected cases. Lung and bronchus cancer is the third most common cancer diagnosis with an estimated 234,580 new cases. [9] 
  • It has been iterated that 92% of U.S. cases of adenocarcinoma of the prostate gland, are diagnosed in men aged, who are aged 55+ years; and in 19.5% in men aged 75+ years. [10]
  • It has been iterated that adenocarcinoma of the prostate gland is found at autopsy in 40% of men who are aged 60+ years [11] 
  • It has been documented that incidental prostate cancer is reported in about 25% of cystoprostatectomies that had been undertaken for the treatment of urinary bladder cancer [12] 
  • It has been iterated that globally, the highest age standardized rates of adenocarcinoma of the prostate gland are in Oceania, North America, Europe [13] 
  • It has been iterated that lower rates of adenocarcinoma can be found in the developing countries and that this lower rates of adenocarcinoma of the prostate gland might be due to different screening programs and diagnostic pathways
  • It has been pointed out that there is a higher incidence of adenoma of the prostate gland in men of African heritage [13]

Sites

  • The sites of the prostate gland that are afflicted by adenocarcinoma had been summated as follows: [7]
  • The majority of adenocarcinoma of prostate gland tumours are stated to be multifocal tumours [14] 
  • It has been stated that 75% to 80% of adenocarcinomas of the prostate gland are found within the posterior / posterolateral peripheral zone of the prostate gland
  • It has been iterated that between about 13% to 20% of adenocarcinomas of the prostate gland are found in the transition (periurethral) zone [15] [16] 
  • It has been pointed out that most clinically significant adenocarcinomas of the prostate gland arise within the peripheral zone of the prostate gland which is sampled by needle biopsies
  • It has been iterated that transition zone prostate cancer is associated with favourable pathology examination features and better recurrence free survival [17] 
  • It has been pointed out that adenocarcinoma of the prostate gland less frequently afflicts the anterior prostate most likely due to inadequate sampling using standard biopsy approach [18] 

Pathophysiology

The pathophysiology of adenocarcinoma of the prostate gland has been summated as follows: [7]

  • It has been iterated that germline variants of primary adenocarcinoma of the prostate gland could increase the risk of developing prostate adenocarcinoma [] 
  • Somatic mutations in genes such as ERG, ETV1/4, FLI1, SPOP, FOXA1, IDH1, PTEN, TP53, MYC, CDH1 had been documented to be associated with adenocarcinoma of the prostate gland [19] [20] 
  • It has been iterated that the most common somatic genomic rearrangement in cases of adenocarcinoma of the prostate gland is fusion of the androgen regulated gene TMPRSS2 with a member of the ETS transcription family [20]

Aetiology

The aetiology of adenocarcinoma of the prostate gland has been summated as follows: [7]

  • Obesity increases the risk for the development of adenocarcinoma of the prostate gland [21] 
  • Non-modifiable risk factors that had been stated to be associated with the development of adenocarcinoma of the prostate gland had been iterated to include the ensuing: age, race and family history [22] 
  • Genetic susceptibility linked to African heritage [22]
  • Increased risk with first degree relative with prostate cancer [22]
  • BRCA2 mutations increase the risk for the development of adenocarcinoma of the prostate gland by 5-fold; BRCA2 associated cancers occur at a lower age and have worse survival outcomes [20] [22] [23] 
  • Additional germline variants associated with increased cancer risk is stated to occur in HOXB13 [20]
  • Increased risk for the development of adenocarcinoma of the prostate gland was stated to be in Lynch syndrome [24] 
  • Numerous single nucleotide polymorphisms (SNPs) that have a low to moderate effect on risk / progression have been identified [7] [25] 
  • It has been iterated that high levels of IGF1 might confer increased risk for the development of adenocarcinoma of the prostate gland [7] [26] 

Clinical features

  • The clinical manifesting features of primary adenocarcinoma of the prostate gland had been summated as follows: [7]
  • It has been iterated that generally adenocarcinoma at the time of initial diagnosis has tended to be asymptomatic unless locally advanced or metastatic
  • It has been stated that adenocarcinoma of the prostate gland is often discovered following investigation of nonspecific lower urinary tract symptoms
  • It has been iterated that in some cases of adenocarcinoma of the prostate gland, during digital rectal examination (DRE), the prostate gland may feel normal or may be enlarged / asymmetrical / hard / as well as have a palpable nodule present

Diagnosis

  • The process of the diagnosis of adenocarcinoma of the prostate gland has been summated as follows: [7]
  • It has been stated that generally prostate cancer is diagnosed by the systematic transrectal ultrasound guided prostate biopsies, and the pathologist then examines the specimens of the prostate biopsies to visualise the prostate cancer diagnostic features of the prostate biopsy specimens [7]
  • It has been iterated that trans-perineal needle biopsies of the prostate gland with targeted biopsies is increasingly undertaken which has tended to be associated with lower risk of infection [7]
  • It has been pointed out that the undertaking of pre-biopsy magnetic resonance imaging (MRI) scan which is ensued by the undertaking of systematic prostate biopsies which is supplemented with targeted biopsies from any radiological abnormality leads to improve the identification of clinically significant prostate cancer than systematic prostate biopsy alone [7] [27] 
  • It has been iterated that incidental prostate cancer is sometimes diagnosed in transurethral resection of prostate gland (TURP) specimens [7]
  • It has been iterated that immunohistochemistry studies of specimens of the prostate gland with basal cell markers (HMWCK, p63) and AMACR is utilised to establish the diagnosis of prostate cancer in equivocal cases [7]

Laboratory

The ensuing summations had been made regarding laboratory tests in the assessment, diagnosis, and follow-ups of individuals who are afflicted by adenocarcinoma of the prostate gland: [7]

  • Raised serum PSA
  • It has been pointed out that different serum PSA level cutoffs had been utilised to prompt the undertaking of prostate needle biopsy [7]
  • It has been iterated that age-specific serum PSA cutoffs, PSA velocity (rate of change in PSA over time) and PSA density (PSA per unit prostate volume - ng/mL/cc) might increase sensitivity and specificity of PSA testing [28] 
  • It has been pointed out that U.S.A. Preventative Services Task Force (USPSTF) had recommended against serum PSA based screening for prostate cancer in men who are aged 70 years and older [7]
  • For men, who are aged between 55 years and 69 years, the taking of periodic serum PSA based screening should be an individual choice based upon the advice of USPSTF [7]
  • It has been iterated that screening in this age group does offer a small potential benefit of reducing the chance of death from prostate cancer in some men; however, many men will experience potential harm [7] [29] 
  • It has been iterated that the American Urological Association (AUA) does not recommend serum PSA screening in men, who under age 40 years or in men aged 40 - 54 years at average risk [7]
  • For men who are aged between 55 years and 59 years, shared decision making has been stated to be desirable [7]
  • For men who are aged 70 years and over 70 years of age or men have less than (< ) 10 years and between 10 years and 15 year life expectancy, serum PSA screening is generally, not recommended [7] [30] 
  • Potential urine biomarker for prostate cancer is PCA3 [7] 

Radiology description

The radiology-image features of prostate cancer had been summated as follows; [7]

  • Ultrasound scan (USS) is generally used to guide prostate biopsies; and prostate cancer may appear upon ultrasound scan images as hypo-echoic but USS is neither sensitive nor specific for the diagnosis of prostate cancer [7]
  • Multiparametric MRI scan is commonly used for the local tumour staging and it may also be used to identify abnormalities for targeting at biopsy of the prostate gland [7]
  • MRI abnormalities are generally reported using either PI-RADS (Prostate Imaging - Reporting and Data System) or Likert score [7]
  • CT scan is used to identify metastatic disease within lymph nodes [7]
  • Bone scan is used to identify bone metastases [7]
  • PET scan is used to detect micro-metastatic disease in selected patients, such as men with raised PSA levels after treatment [7]

Prognostic factors

The factors of prognostication associated with adenocarcinoma of the prostate gland had been summated as follows: [7]

  • Biopsy: with regard to the pathology examination features of the prostate biopsy specimens, the extent of the tumour which has been assessed and documented in terms of mm measurement or percentage core involvement by the tumour, the grade of the tumour (Gleason score and grade group), perineural invasion, extra-prostatic extension, does determine the prognosis associated with the tumour
  • Radical prostatectomy: With regard to radical prostatectomy specimens, it has been iterated that the size of the tumour, the Gleason score of the tumour and the tumour grade group, the stage of the tumour, and the excision margin status of the tumour documenting absence or presence of tumour at the surgical excision margin represent factors that determine the prognosis of the tumour [7]
  • It has been iterated that during pathology examination of the prostate cancer specimen the finding of Cribriform morphology and intraductal carcinoma tends to be associated with invasive prostate cancer are adverse prognostic indicators [7] [31] 
  • It has been iterated that in a case of primary adenocarcinoma of the prostate gland, the finding of a small cell carcinoma component of the tumour is associated with a tumour that portends an aggressive behaviour and the tumour should be treated differently [7]
  • Some expert groups recommend incorporating intraductal component into the Gleason score while others recommend reporting it separately in a comment [7] [32] [33] [34] 

Treatment

  • The treatment of primary adenocarcinoma of prostate gland has been summated as follows: [7]
  • Preoperative risk stratification of adenocarcinoma of the prostate gland is based upon serum PSA level, clinical stage of the tumour, biopsy parameters of the tumour including: the extent of the tumour, the histopathology grade of the tumour, presence and absence and extent of cribriform morphology features of the tumour, intraductal carcinoma, as well as presence or absence of peri-neural invasion [7]
  • Primary treatment options of adenocarcinoma of the prostate gland are based upon pre-operative risk stratification including: [7]
  • Active surveillance
  • Focal therapy (cryotherapy, high intensity ultrasound)
  • Radical prostatectomy
  • Brachytherapy
  • External beam radiotherapy
  • Hormone therapy (e.g., luteinizing hormone releasing hormone [LHRH] analogues, antiandrogens)
  • Orchidectomy (rare in contemporary practice)
  • Chemotherapy (for metastatic disease)
  • Postprostatectomy options:
  • Generally, PSA monitoring and early salvage therapy if rising serum PSA
  • Less commonly adjuvant therapy for high stage disease or margin positivity

Gross description

Macroscopy pathology examination features of adenocarcinoma of prostate gland specimens had been summated as follows: [7]

  • Often macroscopy examination of the prostate gland in carcinoma of prostate tends to demonstrate grossly an inapparent tumour or what would be described no examination features of the prostate gland to suggest cancer
  • At times gross examination of the prostate gland may demonstrate formation of a cream mass

Microscopic (histologic) description

Microscopy pathology examination features of adenocarcinoma of the prostate gland has been summated as follows: [7]

  • Gleason grading of adenocarcinoma of the prostate gland is stated to be based upon the architecture of the tumour [7]
  • It has been iterated that the Gleason grades of the tumour represent a morphological spectrum from well-formed glands (pattern 3) to increasingly complicated glandular proliferations (pattern 4) to almost no glandular differentiation (pattern 5) [7] [35] 
  • Glandular crowding and infiltrative growth pattern [7]
  • Nuclear enlargement, nucleolar prominence [7]
  • Round generally monomorphic nuclei ]7]
  • Amphophilic cytoplasm [7]
  • Mitoses [7]
  • Apoptotic bodies [7]
  • Stromal desmoplasia [7]
  • Intraluminal contents: crystalloids, pink amorphous secretions, blue mucin [7]
  • Glomerulations, collagenous micronodules (mucinous fibroplasia) [7]
  • Absence of basal cell layer (generally requires immunohistochemical confirmation) [7]
  • There had been an extensive history of exploring urine as a source of biomarkers for prostate cancer that had resulted in a variety of urine tests that are in current clinical use. Importantly, at least three tests had demonstrated high sensitivity (~90%) and negative predictive value of about 95% for clinically significant tumours; nevertheless, there had not been widespread adoption of these tests. [36] Conceptual and methodological advances in the field will help to drive the development of novel urinary tests that in turn may lead to a shift in the clinical paradigm for prostate cancer diagnosis and management. [36] [37] 

Cytology description

  • Urine cytology for detecting prostate cancer is stated to have a very low sensitivity [7] [37] 
  • It has been pointed out that urine cytology is not used clinically in the diagnosis of prostate cancer [7]
  • It has been iterated that FNA of metastatic prostate cancer to a lymph node may show micro-acinar complexes / cell clusters / single cells with fragile cytoplasm and prominent nucleoli [7] [38] 
  • Positive stains
  • It has been iterated that tumour cells of adenocarcinoma of the prostate gland upon immunohistochemistry staining studies exhibit positive staining for the ensuing tumour markers: [7]
  • PSA
  • NKX3.1
  • AMACR (P504S, racemase)
  • Prostein (P501S)
  • PSMA
  • Rare tumours may exhibit aberrant expression of p63 [7] [39] [40

Negative stains

It has been iterated that tumour cells of adenocarcinoma of the prostate gland upon immunohistochemistry staining studies exhibit negative staining for the ensuing tumour markers: [7]

  • CK7
  • CK20
  • High molecular weight cytokeratins (34 beta E12, CK5, CK5/6)
  • p63
  • CDX2
  • GATA3
  • TTF1 [41] 

Molecular / cytogenetics description

The molecular / cytogenetics features of adenocarcinoma of the prostate gland had been summated as follows: [7]

  • Prostate cancer is stated to be a heritable disease [7]
  • It has been iterated that a family history of a first degree relative with prostate cancer increases the risk of developing prostate cancer by 2-fold [7] [42 
  • 30 - 40% of familial risk is due to genetic factors [20] 
  • Genetic factors include highly penetrable rare variants and more common low to moderate risk variants [20]
  • Highly penetrant variants occur in BRCA2 and HOXB13 [7]
  • Over 280 SNPs have been identified as prostate cancer risk factors [20] 
  • For most SNPs, the molecular mechanism of cancer association is generally unknown, as they occur in noncoding regions of the genome [20] 
  • Somatic mutations occur in genes such as ERG, ETV1/4, FLI1, SPOP, FOXA1, IDH1, PTEN, TP53, MYC, CDH1 [20][43] 
  • Most common somatic genomic rearrangement is fusion of the androgen regulated gene TMPRSS2 with a member of the ETS transcription family [20]
  • Somatic mutation profiles of prostate cancer are associated with clinical and pathological outcomes [7]
  • There are 7 major subtypes, which are defined by either specific gene fusions of ETS transcription family members (ERG, ETV1, ETV4 and FLI1) or mutations (SPOP, FOXA1, IDH1) [43] 
  • It has been iterated that different sub-types of prostate cancer have different molecular profiles, for example [43]:
    • ETS subset (59% of cases) are enriched in PTEN mutations
    • SPOP mutant subset (11%) of cases have distinct somatic copy number alteration profiles, including deletions of CHD1, 6q and 2q

Differential diagnoses

The differential diagnoses of prostate cancer had been summated as follows: [7]

  • Benign prostate tissue:
  • Pale cytoplasm
  • Corpora amylacea
  • No other intraluminal contents
  • Basal cell marker immunoreactivity
  • Prostate atrophy:
  • Lobular architecture
  • Scant cytoplasm
  • Basal cell marker immunoreactivity
  • Adenosis:
    • Lobular architecture
    • Basal cell marker immunoreactivity (often scattered)
  • Atypical small acinar proliferation (ASAP):
  • Small size
  • Lack of significant cytological atypia, including a lack of macronucleoli
  • High grade prostatic intraepithelial neoplasia (HGPIN):
  • Less architectural atypia
  • Maintained basal cells
  • Post-atrophic hyperplasia:
  • Some glands atrophic
  • Basal cell marker immunoreactivity (often scattered)
  • Partial atrophy:
  • Atrophic glands with abundant lateral pale cytoplasm
  • Irregularly distributed nuclei
  • Basal cell marker immunoreactivity (often scattered)
  • Radiation atypia:
  • Glandular atrophy
  • Nuclear irregularity and pleomorphism
  • Atypical stromal cells
  • Basal cell marker immunoreactivity
  • Urothelial carcinoma:
  • Nuclear irregularity and pleomorphism
  • Hyaline dense eosinophilic cytoplasm
  • Desmoplastic stromal reaction
  • Immunoreactivity for urothelial markers (GATA3, CK7, p63)
  • No expression of prostatic immunomarkers (PSA, PSAP, NKX3.1)

[B] Miscellaneous Narrations from Some Case Reports, Case Series and Studies Related to Irreversible Electroporation of Prostate Cancer 

Prabhakar et al. [1] made the ensuing iterations: 

  • Irreversible electroporation (IRE) is a new and promising focal therapy for the treatment of localized prostate cancer. 
  • they had summarized the literature on IRE for prostate cancer which had been published over the last decade preceding 2024.

Prabhakar et al. [1] searched PubMed and EMBASE with the end date of May 2023 to find relevant publications on prostate cancer ablation using IRE. They included original studies with focal IRE as the primary curative treatment which reported on functional or oncological outcomes were included. They also scanned bibliography of relevant studies to identify suitable articles. Prabhakar et al. [1] summated the results as follows:

  • They had included a total of 14 studies reporting on 899 patients treated with IRE for localized prostate cancer. 
  • Out of all the studies they had reviewed, 77% had reported on recurrence within the zone of ablation, and it had ranged from 0% to 38.9% for in-field and 3.6% to 28% for out-of-field recurrence. 
  • Even though, a standardised follow-up protocol was not followed, all the studies had employed serial prostate-specific antigen monitoring, a multiparametric magnetic resonance imaging, and a biopsy at between 6 months and 12 months pursuant to the IRE -treatment. 
  • Across all the studies, 58% had reported that the urinary continence had returned to the pretreatment levels and 25% had reported a minor decrease in the continence from the baseline at 12-months of follow-up. 
  • Erections sufficient for intercourse had varied from 44% to 75% at the baseline to 55% to 100% at 12-months of follow-up across all the studies.

Prabhakar et al. [1] made the ensuing conclusions:

  • IRE, as a focal therapy, had demonstrated promising results with minimal complications and reasonably effective oncological control, but the data comparing it to the standard of care was still lacking. 
  • Future research should focus upon randomized definitive comparisons between IRE, radical prostatectomy, and radiotherapy.

Blazevski et al. [44] assessed the safety, oncology as well as quality-of-life (QoL) outcomes of focal ablation of apical prostate cancer (PCa) lesions with irreversible electroporation (IRE). Blazevski et al. [44] included patients in the study if they had a PCa lesion within 3 mm of the apical capsule treated with IRE. The IRE procedure was undertaken in their institution by a single urologist. Blazevski et al. [44] collected the QoL and functional data prospectively from patients who had provided consent using the Expanded Prostate Cancer Index Composite (EPIC). The oncology follow-up included the obtaining of 3-month serum PSA levels, mpMRI at 6 months and trans-perineal biopsy at 1-year post treatment. Blazevski et al. [44] summated the results as follows: 

  • A total of 50 patients had apical PCa lesions which were treated between February 2013 and September 2018. 
  • The median follow-up was 44 months. 
  • There were no Clavien-Dindo grade 3 events or higher. 
  • No perioperative complications were documented. 
  • No significant difference was observed in the EPIC urinary or bowel QoL domain between baseline and 12-month post-treatment. 
  • One patient that amounted 2% of the patients required one pad per day for urinary incontinence 12-month post-treatment. 
  • There was a small but significant decline in EPIC sexual QoL (65 at baseline and 59 at 12-month post-IRE). 
  • Out of patients who were potent pre-treatment, 94% had remained potent after their treatments. 
  • The median serum PSA nadir had decreased by 71% (6.25-1.7 ng/mL). 
  • Only one patient which amounted to 2.5% of the patients had in-field residual disease upon pathology examination of his repeat prostate biopsy specimen.

Blazevski et al. [44] concluded that focal ablation using IRE for PCa in the distal apex appeared to be safe and feasible with acceptable early QoL and oncology outcomes.

Yaxley et al. [45] made the ensuing iterations: 

  • Focal irreversible electroporation (IRE) for prostate cancer is aimed to reduce quality of life complications; nevertheless, outcomes data had remained limited. 
  • They had aimed to evaluate the histopathology in-field clearance of prostate cancer at ≥12 months post-IRE.

Yaxley et al. [45] undertook a retrospective review of prospectively acquired data of consecutive patients who had been treated between August 2018 and August 2021. They defined significant recurrence as a ≥6 mm core Gleason 3+3, or ≥Gleason 3+4 with ≥4 mm tumour length. They also analysed a second definition of any focus of International Society of Urological Pathology (ISUP) ≥2. Yaxley et al. [45] summated the results as follows: 

  • The median follow-up of the entire cohort of patients was 23 months and the follow-up had ranged between 3 months and 39 months. 
  • For 64 primary IRE procedures, surveillance biopsy was undertaken in 40 patients out of 50 patients which amounted to 80.0% with ≥12 months follow-up. 
  • Significant in-field recurrence had occurred in 3 patients out of 40 patients which amounted to 7.5% of the patients, or in 4 patients out of 40 patients which amounted to in 10.0% of patients with any focus of ISUP >2. 
  • Significant out-of-field recurrence had occurred in 5 patients out of 40 patients which amounted to in 12.5% of the patients. 
  • In salvage IRE, three patients (3/6, 50.0%) had undetectable prostate-specific antigen levels, two had no residual cancer upon pathology examination of their prostate biopsy specimens and one patient had out-of-field recurrence. 
  • For sexually active men, erectile function was maintained in 24 patients out of 28 patients which amounted to in 85.7% of primary IRE. 
  • No incontinence had developed in primary IRE (0/64).

Yaxley et al. [45] made the ensuing conclusions:

  • Surveillance prostate biopsies are needed to exclude progression despite a normal post-IRE multiparametric magnetic resonance imaging (mpMRI). 
  • Salvage IRE is a promising option for localised recurrence after radiotherapy of prostate cancer with low morbidity.
  • Focal IRE for primary PCa is associated with complete in-field ablation of all cancer in 87.5

Conclusions

  • IRE is a new focal ablative treatment option for localised prostate cancer in carefully selected men. 
  • Published cohorts of treated patients with IRE of localized prostate cancer had reported encouraging short-term oncological and functional outcomes; nevertheless, longer-term data are required in order to validate this treatment before it could be recommended for widespread clinical usage.

Conflict Of Interest

Nil

Acknowledgements

Acknowledgements to: 

Einstein (Sao Paolo): For granting permission for reproduction of figures and contents of their Journal article under the Creative Commons Attribution License with the ensuing copyright iterations: Copyright the authors This content is licensed under a Creative Commons Attribution 4.0 International License 

References

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