Neoadjuvant immunotherapy in early-stage NSCLC: navigating biomarker dilemmas and special population challenges

Neoadjuvant immunotherapy has shown impressive outcomes in treating non-small cell lung cancer (NSCLC) recently due to advancements in immune checkpoint inhibitors (ICIs) research. Neoadjuvant immunotherapy can lower the tumor load, raise the complete surgical (R0) resection rate, and improve clinical outcomes by alleviating the immune system repression caused by tumor cells. This review provides a comprehensive evaluation of neoadjuvant immunotherapy in NSCLC, focusing on: (1) its safety and efficacy profiles, (2) the most recent clinical trial evidence, and (3) critical unresolved challenges including predictive biomarker development, management of driver mutation-positive patients, chronic obstructive pulmonary disease (COPD) comorbidity considerations, and its application in stage III-IVA (oligometastatic) disease. Furthermore, we explore future research directions to optimize neoadjuvant immunotherapy approaches for resectable NSCLC, aiming to guide clinical practice and investigation.