ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY >
Pulse Field Ablation in Oncology: Current Progress and Future Directions
Received date: 2025-08-17
Revised date: 2025-08-28
Accepted date: 2025-09-02
Online published: 2025-11-06
Copyright
Pulsed field ablation (PFA), a non-thermal ablation technique that induces cell death via irreversible electroporation, has emerged as a promising therapeutic strategy for treating tumors located in anatomically complex regions. This review comprehensively examines recent developments in PFA, including its mechanisms foundations, established clinical applications in pancreatic, prostate and liver cancer, and expanding utility with other tumors, etc. Furthermore, we discuss synergistic approaches combining PFA with chemotherapy, immunotherapy, surgery and radiotherapy to augment therapeutic outcomes. In addition, technological innovations—such as robotic assistance, magnetic anchoring, and artificial intelligence—that improve precision and reproducibility are also explored. Despite encouraging clinical results, broader implementation of PFA necessitates higher-quality evidence from large-scale randomized trials and standardized treatment protocols. This review highlights the transformative potential of PFA in oncology while addressing contemporary challenges and future research directions to facilitate clinical translation.
Xie Liting , Zhang Chengyue , Lou Wenjing , Xu Fan , Ma Wenyuan , Jiang Tian’an . Pulse Field Ablation in Oncology: Current Progress and Future Directions[J]. ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY, 2025 , 9(4) : 426 -436 . DOI: 10.26599/AUDT.2025.250099
| [1] | Geboers B , Scheffer HJ , Graybill PM , Ruarus AH , Nieuwenhuizen S , Puijk RS , et al . High-voltage electrical pulses in oncology: irreversible electroporation, electrochemotherapy, gene electrotransfer, electrofusion, and electroimmunotherapy. Radiology 2020; 295: 254-272. |
| [2] | Ma W , Liu H , Xu F , Xu L , Zhang C , Lou W , et al. High-voltage electrical pulses for pancreatic cancer treatment in the era of precision medicine. Int J Surg 2025. |
| [3] | Xu M , Xie LT , Xiao YY , Liang P , Zhao QY , Wang ZM , et al . Chinese clinical practice guidelines for ultrasound-guided irreversible electroporation of liver cancer (version 2022). Hepatobiliary Pancreat Dis Int 2022; 21: 462-471. |
| [4] | Martin RC , 2nd, Kwon D , Chalikonda S , Sellers M , Kotz E , Scoggins C , et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg 2015; 262:486-494; discussion 492-484. |
| [5] | Wang H , Xue W , Yan W , Yin L , Dong B , He B , et al . Extended focal ablation of localized prostate cancer with high-frequency irreversible electroporation: a nonrandomized controlled trial. JAMA Surg 2022; 157: 693-700. |
| [6] | Xu M , Zhang W , Xu D , Dong G , Ren Z , Aji T , et al . Nanosecond pulsed electric field ablation as first-line curative therapy for hepatocellular carcinoma in high-risk locations a prospective multicenter. Int J Surg 2025; 111: 3289-3298. |
| [7] | Ruarus AH , Vroomen L , Geboers B , van Veldhuisen E , Puijk RS , Nieuwenhuizen S , et al . Percutaneous irreversible electroporation in locally advanced and recurrent pancreatic cancer (PANFIRE-2): a multicenter, prospective, single-arm, phase II study. Radiology 2020; 294: 212-220. |
| [8] | Timmer FEF , Geboers B , Ruarus AH , Vroomen L , Schouten EAC , van der Lei S , et al . MRI-guided stereotactic ablative body radiotherapy versus CT-guided percutaneous irreversible electroporation for locally advanced pancreatic cancer (CROSSFIRE): a single-centre, open-label, randomised phase 2 trial. Lancet Gastroenterol Hepatol 2024; 9: 448-459. |
| [9] | Chai W , Tian G , Jiang T . Percutaneous irreversible electroporation for portal vein tumor thrombus: A Case Report. Ultrasound Q 2017; 33: 296-299. |
| [10] | Franken LC , van Veldhuisen E , Ruarus AH , Coelen RJS , Roos E , van Delden OM , et al . Outcomes of irreversible electroporation for perihilar cholangiocarcinoma: a prospective pilot study. J Vasc Interv Radiol 2022; 33: 805-813.e801. |
| [11] | Ringel-Scaia VM , Beitel-White N , Lorenzo MF , Brock RM , Huie KE , Coutermarsh-Ott S , et al . High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity. EBioMedicine 2019; 44: 112-125. |
| [12] | Belfiore MP , Ronza FM , Romano F , Ianniello GP , De Lucia G , Gallo C , et al. Percutaneous CT-guided irreversible electroporation followed by chemotherapy as a novel neoadjuvant protocol in locally advanced pancreatic cancer: Our preliminary experience. Int J Surg 2015;21 Suppl 1:S34-39. |
| [13] | Lafranceschina S , Brunetti O , Delvecchio A , Conticchio M , Ammendola M , Currò G , et al. Systematic review of irreversible electroporation role in management of locally advanced pancreatic cancer. Cancers (Basel) 2019;11. |
| [14] | Campana LG , Daud A , Lancellotti F , Arroyo JP , Davalos RV , Di Prata C , et al. P ulsed electric fields in oncology: a snapshot of current clinical practices and research directions from the 4th world congress of electroporation. Cancers (Basel) 2023;15. |
| [15] | Holland MM , Bhutiani N , Kruse EJ , Weiss MJ , Christein JD , White RR , et al . A prospective, multi-institution assessment of irreversible electroporation for treatment of locally advanced pancreatic adenocarcinoma: initial outcomes from the AHPBA pancreatic registry. HPB (Oxford) 2019; 21: 1024-1031. |
| [16] | Martin RCG , 2nd, White RR , Bilimoria MM , Kluger MD , Iannitti DA , Polanco PM , et al. Effectiveness and safety of irreversible electroporation when used for the ablation of stage 3 pancreatic adenocarcinoma: initial results from the DIRECT registry study. Cancers (Basel) 2024;16. |
| [17] | Geboers B , Timmer F , Vos D , Scheffer H , Bakker J , Ruarus A , et al. Systemic immunomodulation by irreversible electroporation versus stereotactic ablative body radiotherapy in locally advanced pancreatic cancer: the CROSSFIRE trial. J Immunother Cancer 2025;13. |
| [18] | Zhang K , Teoh J , Laguna P , Dominguez-Escrig J , Barret E , Ramon-Borja JC , et al . Effect of focal vs extended irreversible electroporation for the ablation of localized low- or intermediate-risk prostate cancer on early oncological control: a randomized clinical trial. JAMA Surg 2023; 158: 343-349. |
| [19] | Collettini F , Enders J , Stephan C , Fischer T , Baur ADJ , Penzkofer T , et al . Image-guided irreversible electroporation of localized prostate cancer: functional and oncologic outcomes. Radiology 2019; 292: 250-257. |
| [20] | George AK , Miocinovic R , Patel AR , Lomas DJ , Correa AF , Chen DYT , et al. Irreversible electroporation for prostate tissue ablation in patients with intermediate-risk prostate cancer: results from the PRESERVE trial. Eur Urol 2025. |
| [21] | Ma Y , Chen Z , Liang B , Li R , Li J , Li Z , et al . Irreversible electroporation for hepatocellular carcinoma abutting the diaphragm: a prospective single-center study. J Clin Transl Hepatol 2022; 10: 190-196. |
| [22] | Meijerink MR , Ruarus AH , Vroomen L , Puijk RS , Geboers B , Nieuwenhuizen S , et al . Irreversible electroporation to treat unresectable colorectal liver metastases (COLDFIRE-2): a phase II, two-center, single-arm clinical trial. Radiology 2021; 299: 470-480. |
| [23] | Blaise L , Pereira H , Vilgrain V , Sutter O , Gigante E , Walter A , et al . Percutaneous ablation for locally advanced hepatocellular carcinoma with tumor portal invasion. Clin Res Hepatol Gastroenterol 2021; 45: 101731. |
| [24] | Ruys AT , van Haelst S , Busch OR , Rauws EA , Gouma DJ , van Gulik TM . Long-term survival in hilar cholangiocarcinoma also possible in unresectable patients. World journal of surgery 2012; 36: 2179-2186. |
| [25] | Narayanan G , Spano A , Gentile NT , Shnayder-Adams MM , Gurusamy V , Levi DM , et al . Irreversible electroporation as a valid treatment option for hepatic epithelioid hemangioendothelioma: an international multicenter experience. Cardiovasc Intervent Radiol 2024; 47: 883-890. |
| [26] | Tasu JP , Vionnet M , Velasco S , Lafitte L , Poignard C . Percutaneous irreversible electroporation for the treatment of pancreatic insulinoma. Diagn Interv Imaging 2023; 104: 307-308. |
| [27] | Niu L , Li J , Zeng J , Fang G , Zhou L , Xu K , et al . Percutaneous irreversible electroporation for pancreatic VIPoma: a case report. Pancreas 2017; 46: 135-137. |
| [28] | Trimmer CK , Khosla A , Morgan M , Stephenson SL , Ozayar A , Cadeddu JA . Minimally invasive percutaneous treatment of small renal tumors with irreversible electroporation: a single-center experience. J Vasc Interv Radiol 2015; 26: 1465-1471. |
| [29] | Wendler JJ , Ricke J , Pech M , Fischbach F , Jürgens J , Siedentopf S , et al . First delayed resection findings after irreversible electroporation (IRE) of human localised renal cell carcinoma (RCC) in the IRENE pilot phase 2a trial. Cardiovascular and interventional radiology 2016; 39: 239-250. |
| [30] | Wagstaff PG , de Bruin DM , Zondervan PJ , Savci Heijink CD , Engelbrecht MR , van Delden OM , et al . The efficacy and safety of irreversible electroporation for the ablation of renal masses: a prospective, human, in-vivo study protocol. BMC Cancer 2015; 15: 165. |
| [31] | Wendler JJ , Porsch M , Nitschke S , K?llermann J , Siedentopf S , Pech M , et al . A prospective Phase 2a pilot study investigating focal percutaneous irreversible electroporation (IRE) ablation by NanoKnife in patients with localised renal cell carcinoma (RCC) with delayed interval tumour resection (IRENE trial). Contemp Clin Trials 2015; 43: 10-19. |
| [32] | Ricke J , Jürgens JH , Deschamps F , Tselikas L , Uhde K , Kosiek O , et al . Irreversible electroporation (IRE) fails to demonstrate efficacy in a prospective multicenter phase II trial on lung malignancies: the ALICE trial. Cardiovasc Intervent Radiol 2015; 38: 401-408. |
| [33] | Fanta J , Horák P , Marvan J , Ma?ek M , Ka?par M , Pauk N , et al . [The NanoKnife and two successful cases of intracavitary irreversible electroporation of main bronchus tumours]. Rozhl Chir 2012; 91: 625-630 |
| [34] | Meijerink MR , Scheffer HJ , de Bree R , Sedee RJ . Percutaneous irreversible electroporation for recurrent thyroid cancer——a case report. J Vasc Interv Radiol 2015; 26:1180-1182. |
| [35] | Klein N , Zapf S , Gunther E , Stehling M . Treatment of lymph node metastases from gastric cancer with a combination of Irreversible Electroporation and Electrochemotherapy: a case report. Clin Case Rep 2017; 5: 1389-1394. |
| [36] | Kwok N , Lee LK , Arellano RS . Use of irreversible electroporation to treat metastatic pelvic lymphadenopathy. J Vasc Interv Radiol 2016; 27: 1257-1258. |
| [37] | Xu M , Jiang T . First report of successful treatment of cervical lymph node metastasis with irreversible electroporation. Qjm 2023; 116: 385-387. |
| [38] | Jiang T , Zhao Q , Tian G , Chen X , Wu L . Irreversible electroporation ablation of end-stage metastatic retroperitoneal lesions: Report on three cases and literature review. Exp Ther Med 2019; 18: 2243-2249 |
| [39] | Bhutiani N , Agle S , Li Y , Li S , Martin RC . Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma. J Surg Oncol 2016; 114: 181-186. |
| [40] | Neal RE , 2nd, Rossmeisl JH , Jr. D'Alfonso V , Robertson JL , Garcia PA , Elankumaran S , et al. , . In vitro and numerical support for combinatorial irreversible electroporation and electrochemotherapy glioma treatment. Ann Biomed Eng 2014; 42: 475-487 |
| [41] | Li J , Liu F , Gupta S , Li C . Interventional nanotheranostics of pancreatic ductal adenocarcinoma. Theranostics 2016; 6: 1393-1402. |
| [42] | Kotnik T , Rems L , Tarek M , Miklavcic D . Membrane electroporation and electropermeabilization: mechanisms and models. Annu Rev Biophys 2019; 48: 63-91. |
| [43] | Lv Y , Zhang Y , Huang J , Wang Y , Rubinsky B . A study on nonthermal irreversible electroporation of the thyroid. Technol Cancer Res Treat 2019; 18:1533033819876307. |
| [44] | Yang J , Eresen A , Shangguan J , Ma Q , Yaghmai V , Zhang Z . Irreversible electroporation ablation overcomes tumor-associated immunosuppression to improve the efficacy of DC vaccination in a mice model of pancreatic cancer. Oncoimmunology 2021; 10: 1875638. |
| [45] | Narayanan JSS , Ray P , Hayashi T , Whisenant TC , Vicente D , Carson DA , et al . Irreversible electroporation combined with checkpoint blockade and TLR7 stimulation induces antitumor immunity in a murine pancreatic cancer model. Cancer Immunol Res 2019; 7: 1714-1726. |
| [46] | Sugimoto K , Kakimi K , Takeuchi H , Fujieda N , Saito K , Sato E , et al . Irreversible electroporation versus radiofrequency ablation: comparison of systemic immune responses in patients with hepatocellular carcinoma. J Vasc Interv Radiol 2019; 30: 845-853.e6. |
| [47] | Li Q , Li J , Song S , Chen W , Shen X , Li S , et al. Nanoparticle-mediated tumor vaccines for personalized therapy: preparing tumor antigens in vivo or ex vivo? J Mater Chem B 2021; 9:2352-2366. |
| [48] | Xi P , Sun P , Chen M , Yao Z , Zhu Q , Li S , et al . Efficacy of irreversible electroporation combined with immunotherapy versus irreversible electroporation alone in locally advanced pancreatic cancer: a propensity score-matched retrospective study. Front Immunol 2025; 16: 1620988. |
| [49] | Kwon D , McFarland K , Velanovich V , Martin RC . Borderline and locally advanced pancreatic adenocarcinoma margin accentuation with intraoperative irreversible electroporation. Surgery 2014; 156: 910-920. |
| [50] | Ratnayake B , Al-Leswas D , Mohammadi-Zaniani G , Littler P , Sen G , Manas D , et al. Margin accentuation irreversible electroporation in stage III pancreatic cancer: a systematic review. Cancers (Basel) 2021;13. |
| [51] | Tasu JP , Herpe G , Damion J , Richer JP , Debeane B , Vionnet M , et al . Irreversible electroporation to bring initially unresectable locally advanced pancreatic adenocarcinoma to surgery: the IRECAP phase II study. Eur Radiol 2024; 34: 6885-6895. |
| [52] | Martin RCG , 2nd EC , Schoen P , Philips ME , Egger KM , McMasters CR . Impact of margin accentuation with intraoperative irreversible electroporation on local recurrence in resected pancreatic cancer. Surgery 2023; 173: 581-589. |
| [53] | Martin RC , 2nd, McFarland K , Ellis S , Velanovich V . Irreversible electroporation in locally advanced pancreatic cancer: potential improved overall survival. Ann Surg Oncol 2013;20 Suppl 3:S443-449. |
| [54] | Jiang L , Huang X , Hua X , Li Q , Zhang Y , Wang J , et al . Treatment of locally advanced pancreatic cancer with irreversible electroporation and intraoperative radiotherapy. Hepatobiliary Surg Nutr 2024; 13: 1087-1090. |
| [55] | M?nsson C , Brahmstaedt R , Nilsson A , Nygren P , Karlson BM . Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy. Eur J Surg Oncol 2016; 42: 1401-1406. |
| [56] | Ma YY , Leng Y , Xing YL , Li HM , Chen JB , Niu LZ . Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer. World J Clin Cases 2020; 8: 5564-5575. |
| [57] | van Veldhuisen E , Vroomen LG , Ruarus AH , Derksen TC , Busch OR , de Jong MC , et al . Value of CT-guided percutaneous irreversible electroporation added to FOLFIRINOX chemotherapy in locally advanced pancreatic cancer: a post hoc comparison. J Vasc Interv Radiol 2020; 31: 1600-1608. |
| [58] | Oikonomou D , Karamouzis MV , Moris D , Dimitrokallis N , Papamichael D , Kountourakis P , et al . Irreversible electroporation (IRE) combined with chemotherapy increases survival in locally advanced pancreatic cancer (LAPC). Am J Clin Oncol 2021; 44: 325-330. |
| [59] | Lin M , Alnaggar M , Liang S , Wang X , Liang Y , Zhang M , et al . An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer. Oncotarget 2017; 8: 101795-101807. |
| [60] | Yang Y , Qin Z , Du D , Wu Y , Qiu S , Mu F , et al . Safety and short-term efficacy of irreversible electroporation and allogenic natural killer cell immunotherapy combination in the treatment of patients with unresectable primary liver cancer. Cardiovasc Intervent Radiol 2019; 42: 48-59. |
| [61] | Pan Q , Hu C , Fan Y , Wang Y , Li R , Hu X . Efficacy of irreversible electroporation ablation combined with natural killer cells in treating locally advanced pancreatic cancer. J BUON 2020; 25: 1643-1649 |
| [62] | Zhang T , Chen J , Niu L , Liu Y , Ye G , Jiang M , et al . Clinical safety and efficacy of locoregional therapy combined with adoptive transfer of allogeneic gammadelta T cells for advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Vasc Interv Radiol 2022; 33: 19-27.e3. |
| [63] | Martin RC , 2nd Y , Li EA , Shore DA , Malik H , Li X , et al . Irreversible electroporation and beta-glucan-induced trained innate immunity for treatment of pancreatic ductal adenocarcinoma: a phase II study. J Am Coll Surg 2025; 240: 351-361. |
| [64] | Davis JM , Salibi PN , Motz BM , Vrochides D , McKillop IH , Iannitti DA . Irreversible electroporation-assisted resection for locally advanced pancreas cancer. Surg Innov 2023; 30: 332-339. |
| [65] | Li Q , Gao X , Zhang Y , Han X , Li Z , Zhang Y , et al . Magnetic anchoring and guidance-assisted endoscopic irreversible electroporation for gastric mucosal ablation: a preclinical study in canine model. Surg Endosc 2021; 35: 5665-5674. |
| [66] | Ren F , Li Q , Hu L , Yan X , Gao Z , Zhang J , et al . Safety and efficacy of magnetic anchoring electrode-assisted irreversible electroporation for gastric tissue ablation. Surg Endosc 2020; 34: 580-589. |
| [67] | L'Huillier R , Dumortier J , Mastier C , Cayot B , Chambon C , Benech N , et al . Robotic-assisted percutaneous irreversible electroporation for the treatment of hepatocellular carcinoma. Diagn Interv Imaging 2023; 104: 615-617. |
| [68] | Wardhana G , Fütterer JJ , Abayazid M . IRE made easy: introducing the robotic grid system for multiple parallel needle insertion in irreversible electroporation treatment. Int J Comput Assist Radiol Surg 2024; 19: 1517-1526. |
| [69] | Wardhana G , Mak YX , Abayazid M , Fütterer JJ , Ieee, editors. Design and characterization of a multiple needle insertion MRI-guided robot for irreversible electroporation (IRE) treatment. 9th IEEE RAS/EMBS international conference for biomedical robotics and biomechatronics (BioRob); 2022 Aug 21-24; Seoul Natl Univ, Seoul, SOUTH KOREA2022. |
| [70] | Fuhrmann I , Probst U , Wiggermann P , Beyer L . Navigation systems for treatment planning and execution of percutaneous irreversible electroporation. Technol Cancer Res Treat 2018; 17:1533033818791792. |
| [71] | Beyer LP , Pregler B , Michalik K , Niessen C , Dollinger M , Müller M , et al . Evaluation of a robotic system for irreversible electroporation (IRE) of malignant liver tumors: initial results. Int J Comput Assist Radiol Surg 2017; 12: 803-809. |
| [72] | He XF , Xiao YY , Zhang X , Zhang XB , Zhang X , Wei YT , et al . Preliminary clinical application of the robot-assisted CT-guided irreversible electroporation ablation for the treatment of pancreatic head carcinoma. Int J Med Robot 2020; 16: e2099. |
| [73] | Rao S , Bui TL , Sasani A , Sadeghi B , Macherla A , Houshyar R , et al . Irreversible electroporation for pancreatic cancer using intraprocedural cone-beam computed tomography fusion navigation: a case report. J Med Case Rep 2021; 15: 566. |
| [74] | Zhang K , Ru J , Wang W , Xu M , Mu L , Pan J , et al . ViT-based quantification of intratumoral heterogeneity for predicting the early recurrence in HCC following multiple ablation. Liver Int 2025; 45: e16051. |
| [75] | Martin II RCG , Durham AN , Besselink MG , Iannitti D , Weiss MJ , Wolfgang CL , et al . Irreversible electroporation in locally advanced pancreatic cancer: A call for standardization of energy delivery. Journal of Surgical Oncology 2016; 114: 865-871. |
| [76] | Pech M , Janitzky A , Wendler JJ , Strang C , Blaschke S , Dudeck O , et al . Irreversible electroporation of renal cell carcinoma: a first-in-man phase I clinical study. CardioVascular and Interventional Radiology 2011; 34: 132-138. |
| [77] | Dong L , Tong Z , Shi B , Zhuang Q , Li Y , Gong M , et al . The efficacy and safety of high-frequency irreversible electroporation for benign prostatic hyperplasia: a randomized controlled open-label multicenter trial. Chinese Journal of Urology 2025; 46: 161-165 |
| [78] | Rudno-Rudzińska J , Kielan W , Guziński M , Kulbacka J . Effects of calcium electroporation, electrochemotherapy, and irreversible electroporation on quality of life and progression-free survival in patients with pancreatic cancer: IREC clinical study. Advances in Clinical and Experimental Medicine 2021; 30: 765. |
/
| 〈 |
|
〉 |
Share: WeChat
Copyright ©2018 Advanced Ultrasound in Diagnosis and Therapy
|
Advanced Ultrasound in Diagnosis and Therapy (AUDT)
is licensed under a Creative Commons Attribution 4.0 International License.