A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

Numerical simulation of neural excitation during brain tumor ablation by microsecond pulses.

Replacing monopolar pulse with bipolar pulses of the same energized time can minimize unnecessary neurological side effects during irreversible electroporation (IRE). An improved neural excitation model that considers dynamic conductivity and thermal effects during brain tumor IRE ablation was proposed for the first time in this study. Nerve fiber excitation during IRE ablation by applying a monopolar pulse (100 µs) and a burst of bipolar pulses (energized time of 100 µs with both the sub-pulse length and interphase delay of 1 µs) was investigated. Our results suggest that both thermal effects and dynamic conductivity change the onset time of action potential (AP), and dynamic conductivity also changes the hyperpolarization amplitude. Considering both thermal effects and dynamic conductivity, the hyperpolarization amplitude in nerve fibers located 2 cm from the tumor center was reduced by approximately 23.8 mV and the onset time of AP was delayed by approximately 17.5 µs when a 500 V monopolar pulse was applied. Moreover, bipolar pulses decreased the excitable volume of brain tissue by approximately 68.8 % compared to monopolar pulse. Finally, bipolar pulses cause local excitation with lesser damage to surrounding healthy tissue in complete tumor ablation, demonstrating the potential benefits of bipolar pulses in brain tissue ablation.

Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience.

PURPOSE: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment. MATERIAL AND METHODS: Between 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm). RESULTS: IRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement. CONCLUSION: The current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.

IRE made easy: introducing the robotic grid system for multiple parallel needle insertion in irreversible electroporation treatment.

PURPOSE: Accurate needle placement is crucial for successful tumor treatment using the irreversible electroporation (IRE) method. Multiple needles are inserted around the tumor, ideally in parallel, to achieve uniform electric field distribution. This paper presents a robot utilizing a grid system to enable multiple needles insertion while maintaining parallelism between them. METHODS: The robotic system has two degrees of freedom, which allow for the adjustment of the grid system to accommodate targeting lesions in various positions. The robot's performance was evaluated by testing its accuracy across various configurations and target depth locations, as well as its ability to maintain the needle parallelism. RESULTS: The robot has dimensions of ϕ 134 mm and a height of 46 mm, with a total weight of 295 g. The system accuracy test showed that the robot can precisely target points across different target depths and needle orientations, with an average error of 2.71 ± 0.68 mm. Moreover, multiple insertions at different grid locations reveal needle orientation deviations typically below 1 ∘ . CONCLUSION: This study presented the design and validation of a robotic grid system. The robot is capable of maintaining insertion accuracy and needle parallelism during multiple needle insertions at various robot configurations. The robot showed promising results with limited needle deviation, making it suitable for IRE procedures.

Safety and Effectiveness of Irreversible Electroporation in Lymph Node Metastases.

PURPOSE: Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases. MATERIALS AND METHODS: An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS). RESULTS: Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively. CONCLUSION: IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.

Pulsed Field Ablation and Neurocardiology: Inert to Efferents or Delayed Destruction?

Background: The therapeutic use of irreversible electroporation in clinical cardiac laboratories, termed pulsed field ablation (PFA), is gaining pre-regulatory approval momentum among rhythm specialists for the mitigation of arrhythmogenic substrate without increased procedural risk. Though electroporation has been utilized in other branches of science and medicine for decades, apprehension regarding all the possible off-target complications of PFA have yet to be thoroughly identified and investigated. Methods: This brief review will summarize the preclinical and adult clinical data published to date on PFA's effects on the autonomic system that interplays closely with the cardiovascular system, termed the neurocardiovascular system. These data are contrasted with the findings of efferent destruction secondary to thermal cardiac ablation modalities, namely radiofrequency energy and liquid nitrogen-based cryoablation. Results: In vitro neurocardiology findings, in vivo neurocardiology findings, and clinical neurocardiology findings to date nearly unanimously support the preservation of a critical mass of perineural structures and extracellular matrices to allow for long-term nervous regeneration in both cardiac and non-cardiac settings. Conclusions: Limited histopathologic data exist for neurocardiovascular outcomes post-PFA. Neuron damage is not only theoretically possible, but has been observed with irreversible electroporation, however regeneration is almost always concomitantly described.

Biphasic Regulation of Apoptosis Following Gastric Irreversible Electroporation Using Tissue Immunohistochemistry of Activated Caspase-3 with TUNEL Method.

The regulation of apoptosis is the primary goal of ablation therapy. Irreversible electroporation (IRE) is a promising non-thermal tissue ablation-based therapy that induces apoptosis by manipulating electrical conditions. This study aimed to investigate IRE-induced gastric tissue apoptosis in response to changes in the electric field intensity, followed by the repair process. Among the 52 rats used in this study, 24 were used to explore apoptosis, and 28 were used to study regeneration. The apoptosis-to-necrosis ratio of the electrical field strength was evaluated using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3 immunohistochemistry. The size of IRE-induced ulcers in the gastric tissue continuously increased with increasing electrical intensity (r2 = 0.830, p < 0.001). The level of apoptosis gradually decreased after peaking at 200 V (1000 V/cm). The size of the 400 V-ablated ulcers continued to decrease, and they were not visible by day 14. The proliferation and migration of epithelial cells with fibroblasts were observed on day 3 and augmented on day 7 post-ablation. This investigation demonstrated the biphasic activation of apoptosis with respect to the electrical field strength. Visually and histologically, IRE-induced gastric ulcers demonstrated complete tissue regeneration after two weeks.

The Induction of Combined Hyperthermal Ablation Effect of Irreversible Electroporation with Polydopamine Nanoparticle-Coated Electrodes.

Irreversible electroporation (IRE) is a prominent non-thermal ablation method widely employed in clinical settings for the focal ablation therapy of solid tumors. Utilizing high-voltage, short-duration electric pulses, IRE induces perforation defects in the cell membrane, leading to apoptotic cell death. Despite the promise of irreversible electroporation (IRE) in clinical applications, it faces challenges concerning the coverage of target tissues for ablation, particularly when compared to other thermal ablation therapies such as radiofrequency ablation, microwave ablation, and cryoablation. This study aims to investigate the induced hyperthermal effect of IRE by applying a polydopamine nanoparticle (Dopa NP) coating on the electrode. We hypothesize that the induced hyperthermal effect enhances the therapeutic efficacy of IRE for cancer ablation. First, we observed the hyperthermal effect of IRE using Dopa NP-coated electrodes in hydrogel phantom models and then moved to in vivo models. In particular, in in vivo animal studies, the IRE treatment of rabbit hepatic lobes with Dopa NP-coated electrodes exhibited a two-fold higher increase in temperature (ΔT) compared to non-coated electrodes. Through a comprehensive analysis, we found that IRE treatment with Dopa NP-coated electrodes displayed the typical histological signatures of hyperthermal ablation, including the disruption of the hepatic cord and lobular structure, as well as the infiltration of erythrocytes. These findings unequivocally highlight the combined efficacy of IRE with Dopa NPs for electroporation and the hyperthermal ablation of target cancer tissues.

Electroporation in Translational Medicine: From Veterinary Experience to Human Oncology.

Electroporation (EP) is a broadly accepted procedure that, through the application of electric pulses with appropriate amplitudes and waveforms, promotes the delivery of anticancer molecules in various oncology therapies. EP considerably boosts the absorptivity of targeted cells to anticancer molecules of different natures, thus upgrading their effectiveness. Its use in veterinary oncology has been widely explored, and some applications, such as electrochemotherapy (ECT), are currently approved as first-line treatments for several neoplastic conditions. Other applications include irreversible electroporation and EP-based cancer vaccines. In human oncology, EP is still mostly restricted to therapies for cutaneous tumors and the palliation of cutaneous and visceral metastases of malignant tumors. Fields where veterinary experience could help smooth the clinical transition to humans include intraoperative EP, interventional medicine and cancer vaccines. This article recapitulates the state of the art of EP in veterinary and human oncology, recounting the most relevant results to date.

Pulsed field ablation: A promising approach for ventricular tachycardia ablation.

Radiofrequency ablation (RFA) has been a central therapeutic strategy for ventricular tachycardia (VT). However, concerns about its long-term effectiveness and complications have arisen. Pulsed field ablation (PFA), characterized by its nonthermal, highly tissue-selective ablation technique, has emerged as a promising alternative. This comprehensive review delves into the potential advantages and opportunities presented by PFA in the realm of VT, drawing insights from both animal experimentation and clinical case studies. PFA shows promise in generating superior lesions within scarred myocardial tissue, and its inherent repetition dependency holds the potential to enhance therapeutic outcomes. Clinical cases underscore the promise of PFA for VT ablation. Despite its promising applications, challenges such as catheter maneuverability and proarrhythmic effects require further investigation. Large-scale, long-term studies are essential to establish the suitability of PFA for VT treatment.

Ultrasound-guided percutaneous high-frequency irreversible electroporation in porcine livers using four electrode needles: A feasibility and safety study.

BACKGROUND: Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high-frequency irreversible electroporation (H-FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound-guided percutaneous H-FIRE using four electrode needles in porcine livers. METHODS: Twelve experimental pigs underwent percutaneous H-FIRE ablation using a compound steep-pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast-enhanced ultrasound (CEUS), contrast-enhanced magnetic resonance imaging (MRI), and hematoxylin-eosin staining were performed to evaluate the ablation performance. RESULTS: Ultrasound-guided percutaneous H-FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H-FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. CONCLUSIONS: This study demonstrated the feasibility and safety of ultrasound-guided percutaneous H-FIRE ablation in porcine livers in vivo, and proposed a four-needle method to optimize its clinical application.

Local Treatment of Colorectal Liver Metastases in the Presence of Extrahepatic Disease: Survival Outcomes from the Amsterdam Colorectal Liver Met Registry (AmCORE).

BACKGROUND: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites. METHODS: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS). RESULTS: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029-2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017-3.841, p = 0.041). CONCLUSIONS: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases.

Personalized Treatment Strategy in "Low-Risk Prostate Cancer Active Surveillance Candidates" Using Irreversible Electroporation: Prospective Evaluation of Feasibility, Morbidity, Functional and Oncological Outcomes.

PURPOSE: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in "active surveillance (AS)" candidates refusing standard treatment options. MATERIALS AND METHODS: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). RESULTS: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. CONCLUSIONS: Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

Irreversible Electroporation of the Hepatobiliary System: Current Utilization and Future Avenues.

Liver cancer remains a leading cause of cancer-related deaths worldwide despite numerous advances in treatment. While surgical resection remains the gold standard for curative treatment, it is only possible for a minority of patients. Thermal ablation is an effective option for the treatment of smaller tumors; however, its use is limited to tumors that are not located in proximity to sensitive structures due to the heat sink effect and the potential of thermal damage. Irreversible electroporation (IRE) is a non-thermal ablative modality that can deliver targeted treatment and the effective destruction of tumors that are in close proximity to or even surrounding vascular or biliary ducts with minimal damage to these structures. IRE produces short pulses of high-frequency energy which opens pores in the lipid bilayer of cells leading to apoptosis and cell death. IRE has been utilized clinically for over a decade in the treatment of liver cancers with multiple studies documenting an acceptable safety profile and high efficacy rates.

Electroporación irreversible: ampliando las fronteras de la ablación / Irreversible electroporation: Beyond the limits of tumor ablation

La electroporación irreversible o IRE (irreversible electroporation) es una técnica de ablación tumoral no térmica basada en la aplicación de pulsos eléctricos de alto voltaje entre pares de agujas insertadas alrededor de un tumor. La corriente generada favorece la creación de nanoporos en la membrana plasmática, desencadenando la apoptosis. Por ello, la IRE puede utilizarse de manera segura en localizaciones cercanas a estructuras vasculares delicadas, contraindicadas para el resto de técnicas termoablativas. Actualmente la IRE se emplea con éxito para la ablación de tumores en páncreas, riñón e hígado y, de manera muy extendida, como opción terapéutica focal para el cáncer de próstata. La necesidad de un manejo anestésico específico y la colocación precisa y en paralelo de múltiples agujas implican un alto nivel de complejidad, siendo necesaria una gran experiencia del equipo intervencionista. No obstante, se trata de una técnica muy prometedora con una gran capacidad inmunológica sistémica que puede provocar un efecto a distancia del tumor tratado (efecto abscopal).(AU)

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).(AU)

Irreversible Electroporation-Induced Inflammation Facilitates Neutrophil-Mediated Drug Delivery to Enhance Pancreatic Cancer Therapy.

Pancreatic cancer is a deadly disease with a five-year overall survival rate of around 11%. Chemotherapy is a cornerstone in the treatment of this malignancy, but the intratumoral delivery of chemotherapy drugs is impaired by the highly fibrotic tumor-associated stroma. Irreversible electroporation (IRE) is an ablative technique for treating locally advanced pancreatic cancer. During a typical IRE procedure, high-intensity electric pulses are released to kill tumor cells through the irreversible disruption of the cytoplasm membranes. IRE also induces rapid tumor infiltration by neutrophils and offers an opportunity for neutrophil-mediated drug delivery. We herein showed that the IRE-induced neutrophil trafficking was facilitated by the upregulation of neutrophil chemotaxis and migration as well as the release of several chemoattractants. Doxorubicin-loaded bovine serum albumin nanoparticles were prepared and loaded into neutrophils at a ratio of 9.9 ± 1.2 to 11.7 ± 2.0 pg of doxorubicin per cell. The resultant formulation (NP@NEs) efficiently accumulated in the IRE-treated KPC-A377 murine pancreatic tumors with an uptake value of 10.7 ± 1.5 (percent of injected dose per gram of tissue, abbreviated as %ID/g) at 48 h after intravenous injection. In both Panc02 and KPC-A377 murine pancreatic tumor models, the combination of IRE + NP@NEs inhibited tumor growth more effectively than either monotherapy. The tumors treated with the combination also exhibited the lowest frequency of Ki67+ proliferating cells and the highest abundance of terminal deoxynucleotidyl transferase dUTP nick end labeling+ (TUNEL+) apoptotic cells among the experiment groups. Minimal treatment-associated toxicity was observed. Our findings suggest that neutrophil-mediated delivery of chemotherapy drugs is a useful tool to enhance the response of pancreatic cancer to IRE.

Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma.

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.

Irreversible Electroporation (IRE) for Prostate Cancer (PCa) Treatment: The State of the Art.

We evaluated the most recent research from 2000 to 2023 in order to deeply investigate the applications of PCa IRE, first exploring its usage with primary intent and then salvage intent. Finally, we discuss the differences with other focal PCa treatments. In the case of primary-intent IRE, the in-field recurrence is quite low (ranges from 0% to 33%). Urinary continence after the treatment remains high (>86%). Due to several different patients in the studies, the preserved potency varied quite a lot (59-100%). Regarding complications, the highest occurrence rates are for those of Grades I and II (20-77% and 0-29%, respectively). Grade III complications represent less than 7%. Regarding the specific oncological outcomes, both PCa-specific survival and overall survival are 100%. Metastasis-free survival is 99.6%. In a long-term study, the Kaplan-Meier FFS rates reported are 91% at 3 years, 84% at 5 years, and 69% at 8 years. In the single study with salvage-intent IRE, the in-field recurrence was 7%. Urinary continence was still high (93%), but preserved potency was significantly lower than primary-intent IRE patients (23%). In addition, Grade III complications were slightly higher (10.8%). In conclusion, in males with localized low-intermediate-risk prostate cancer, IRE had an excellent safety profile and might have positive results for sexual and urinary function.

Focal Minimally Invasive Treatment in Localized Prostate Cancer: Comprehensive Review of Different Possible Strategies.

BACKGROUND: Focal therapy is a promising, minimally invasive method for the treatment of patients with localized prostate cancer. According to the existing literature, there is growing evidence for positive functional outcomes and oncological effectiveness. The aim of this review is to evaluate the technical efficacy of three minimally invasive techniques (cryoablation, electroporation, and microwave ablation) and their impact on quality of life in patients with prostate cancer. METHODS: Studies between January 2020 and July 2023 were selected using PubMed, Embase, and The Cochrane Library and analyzed following PRISMA guidelines; they have not been registered. RESULTS: Twenty-three studies investigating three different sources of energy to deliver focal therapy were found. Thirteen studies evaluated the performance of the cryoablation therapy, seven studies of the irreversible electroporation, and three studies of microwave ablation option. The majority of studies were retrospective cohort studies. Cryoablation showed excellent oncological outcomes for low-grade prostate cancer, whether performed on the lesion, on the hemigland, or on the entire gland, with the best results obtained for patients with intermediate risk. Irreversible electroporation showed promising oncological outcomes with no significant changes in functional outcomes. Microwave ablation showed great early functional outcomes. CONCLUSIONS: The oncological effectiveness of minimally invasive treatment in comparison to standard of care is still under investigation, despite encouraging results in terms of functional outcomes improvement and adverse events reduction. More comprehensive research is needed to fully understand the function of minimally invasive treatment in patients with localized PCa.

Irreversible electroporation: Beyond the limits of tumor ablation.

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).