Defining the abscopal effect in non-small cell lung cancer in the era of immunotherapy and lung ablation treatment: a narrative review

The abscopal effect, first described in 1953, refers to the regression of distant, non-irradiated tumors following localized therapy. Historically considered rare, interest in this phenomenon has increased with the introduction of immunotherapy and local treatments for non-small cell lung cancer (NSCLC). This review summarizes the current evidence on the pathophysiology, clinical observations, and assessment of the abscopal effect in NSCLC following radiotherapy, lung ablation, and combined multimodality therapies. Preclinical and early clinical studies suggest that radiotherapy and ablative techniques such as cryoablation, microwave ablation, and pulsed electric field therapy may induce immunogenic cell death, leading to the release of tumor antigens and danger-associated molecular patterns that can activate systemic antitumor immune responses. When combined with immune checkpoint inhibitors, these local therapies may enhance immune activation, potentially improving both local and distant tumor control. However, recognition of abscopal effects remains inconsistent, largely due to limitations of conventional response assessment criteria. While iRECIST partly captures atypical response patterns, unequivocal out-of-field tumor regression is not systematically recorded in most clinical trials. The available evidence, primarily from preclinical models and early-phase studies, suggests that the true incidence of abscopal effects in NSCLC may be underrecognized. Accordingly, we propose a working definition of the abscopal effect in NSCLC: the regression (complete or partial response by iRECIST) of one or more non-irradiated lesions distant from the primary treatment site, occurring after localized therapy with or without systemic treatment, and confirmed by follow-up imaging within 4–8 weeks. Establishing standardized terminology and assessment criteria will be essential for accurately identifying and integrating potential abscopal responses in future NSCLC research and clinical practice.