Irreversible Electroporation (IRE) in Oncology
Irreversible Electroporation (IRE) in Oncology
Irreversible electroporation (IRE) has established a clinical niche as a nonthermal ablation technique for eradicating unresectable tumors, particularly those near critical vascular structures such as blood vessels, nerves, and ducts. This advantage has driven rapid clinical adoption of IRE since its introduction to the clinic in 2010, with over 100 clinical trials registered worldwide today. IRE has proven particularly effective in cancers of the pancreas, liver, and prostate, where tumors often border sensitive structures that limit surgical candidacy and the use of thermal ablation modalities.
Both locally advanced pancreatic cancer (LAPC), which is typically unresectable, and borderline resectable pancreatic cancer (BRPC), often present the largest opportunity for IRE to drastically improve clinical outcomes. Proximity of the pancreas to the celiac trunk, hepatic artery, and superior mesenteric vessels limits surgical candidacy to fewer than 20% of patients and causes high morbidity rates with thermal ablation. Initial results from a recent clinical trial link adding IRE to induction chemotherapy for Stage 3 pancreatic cancer to nearly doubling median overall survival compared with chemotherapy alone (18 months vs. 10 months, p<0.0001) . Liver cancer follows a similar pattern with hepatocellular carcinoma (HCC), the third leading cause of cancer-related death worldwide, accounting for over 80% of primary liver tumors. The liver is also a frequent site of metastasis, especially from colorectal cancer. Standard treatment approaches for HCC and colorectal liver metastases (CRLM) include chemoradiation and surgical resection, which are often limited due to anatomical location or proximity to critical structures. In a study of unresectable CRLMs abutting the portal and hepatic veins, IRE achieved a median overall survival of 40.4 months . Prostate cancer presents a different challenge: although the 5-year relative survival rate approaches ~97% for all stages combined, contemporary treatment (e.g., active surveillance, radical prostatectomy, and radiation) often causes urinary incontinence and sexual dysfunction. Two-year outcomes from the PRESERVE clinical trial show durable oncologic control for intermediate-risk patients while preserving these structures and reducing the risk of complications . Hundreds of published research articles have demonstrated safe, effective treatment of these tumors using IRE, while feasibility in treating other solid tumors like lung and brain has also been demonstrated .
Interestingly, beyond direct tumor destruction, IRE appears to activate the immune system. Several studies report that cancerous cells killed by IRE release DAMPs and antigens that can stimulate immune cell recruitment to clear the primary tumor and reduce distant metastasis . Researchers are now combining IRE with immunotherapies to try to sustain and amplify this response, a strategy that has shown early success in both animal models and patients .
IRE was first described as a viable option for controlled tissue destruction just two decades ago. In that short span, it has reshaped treatment for soft-tissue tumors once deemed inoperable; however, significant gaps remain. Treatment protocols vary across institutions, imaging tools for confirming complete ablation are still evolving, and changes to tumor microenvironment post-IRE have only recently begun to be investigated. Continued research and collaboration between industry partners, clinicians, and researchers will be essential to closing these gaps.
— Contributed by Arianna E. Sanchez, Julio P. Arroyo, Rafael V. Davalos