The role of pulsed electric field therapy in non-small cell lung cancer: a narrative review of a novel minimally invasive intervention.

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung carcinoma cases and is often diagnosed at an advanced stage, leading to poor prognosis. Local tumor ablation is an emerging treatment option; however, thermal ablation techniques, such as radiofrequency ablation (RFA) or microwave ablation (MWA), can have many adverse events, such as a negative impact on the extracellular matrix (ECM) architecture, promoting tumor progression. Pulsed electric field (PEF) therapy is a non-thermal modality that induces electrostimulatory pulses, which can preserve the ECM architecture while stimulating anti-tumor immune responses. This narrative review evaluates the safety, efficacy, and immunomodulatory potential of PEF therapy in NSCLC. Methods: A comprehensive literature search was conducted in Google Scholar, MEDLINE, Embase, Scopus, PubMed, Web of Science, UpToDate, and the Cochrane Library through October 1, 2025. Eligible studies included adult patients (≥18 years) with histologically confirmed NSCLC treated with PEF. Two independent reviewers screened studies and extracted data on patient demographics, tumor characteristics, treatment modalities, adverse events, and outcomes. Key Content and Findings: Eleven studies (249 patients; 4 prospective, 7 retrospective) were included. Median patient age ranged from 53.5 to 72 years. PEF was delivered percutaneously (7 studies) or bronchoscopically (4 studies). PEF monotherapy was reported in eight studies, while PEF in combination with other therapies (stereotactic body radiotherapy, systemic therapy, or surgery) was studied in three papers. Adverse events were mostly mild to moderate; pneumothorax was the most common complication and occurred mainly in percutaneously treated patients (0.6-33.3%). Severe adverse events were rare, and no treatment-related mortality occurred. Treatment responses were heterogeneous: complete responses (CRs) occurred in 16-40% of patients in early-phase trials, with stable disease (SD) in 36-50%. In a propensity-matched cohort, PEF therapy for stage IV NSCLC showed superior 1-year progression-free survival (PFS; 63.2% Conclusions: PEF may play a role in stimulating an anti-tumor response and represents a promising, safe, non-thermal ablation modality for NSCLC treatment. It preserves ECM integrity while inducing local and systemic immunomodulatory effects. Early clinical evidence suggests potential efficacy. Nevertheless, randomized controlled trials are required to confirm clinical benefit and identify the patient populations most likely to benefit from PEF therapy.