A New Era, New Risks: The Cardio-Oncology Perspective on Immunotherapy in Non-Small Cell Lung Cancer

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. In recent years, mortality rates have declined due to antismoking policies, earlier detection, and the advent of targeted therapies and immunotherapy, particularly for non-small cell lung cancer (NSCLC), which accounts for 85% of all cases. With improved survival, however, LC patients are increasingly exposed to competing causes of mortality, among which cardiovascular disease (CVD) is highly prevalent, affecting 30–50% of patients and contributing to nearly 30% of deaths. This burden reflects both shared risk factors and the cardiotoxic potential of radiotherapy, chemotherapy, and immunotherapy. Beyond acute adverse cardiovascular events during treatment, real-world data indicate that immune checkpoint inhibitors (ICIs) may also exert chronic cardiovascular effects, significantly accelerating the atherosclerotic process in multimorbid patients. These findings underscore the importance of accurate baseline assessment and aggressive management of cardiovascular risk factors in LC patients—particularly in the adjuvant and neoadjuvant settings, where longer survival is anticipated. Moreover, long-term monitoring should be implemented through a tailored, multiparametric strategy that integrates novel biomarkers and advanced artificial intelligence–assisted imaging techniques. Achieving this ambitious goal requires the close collaboration of a multidisciplinary team, with cardiologists playing a pivotal role. This review will address the complexity of LC patients, focusing on the interplay of cardio-immuno-metabolic factors, summarizing the cardiovascular impact of immunotherapy across metastatic, locally advanced, and perioperative settings, and outlining practical strategies for the management of these vulnerable patients.