Navigating Multimodality Therapy in Non-Small Cell Lung Cancer: Neoadjuvant-Only Versus Perioperative Immunotherapy,...

Neoadjuvant and perioperative immunotherapy have redefined the treatment landscape for select patients with early-stage and locally-advanced resectable non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis combined with platinum-based chemotherapy have achieved substantially higher rates of pathologic complete response and major pathologic response than chemotherapy alone, translating into meaningful improvements in event-free survival and, in select trials, overall survival. Despite this progress, several clinically important questions remain unanswered, including the relative value of neoadjuvant versus perioperative approaches, the optimal sequencing and duration of therapy, and how best to tailor treatment according to tumor biology, host features, and risk of disease recurrence. Emerging biomarkers such as PD-L1 expression, circulating tumor DNA dynamics, and pathologic response may help refine treatment selection although their role in routine decision making is still evolving. The integration of immunotherapy into curative-intent treatment also has important multidisciplinary implications. Accurate staging, appropriate biomarker testing, thoughtful considerations for multimodal therapy integration throughout the perioperative setting, high-quality surgical resection, and careful response assessment remain essential to maximize the benefit of systemic therapy. This review summarizes the current evidence supporting neoadjuvant and perioperative immunotherapy in resectable NSCLC and discusses key biomarkers, unresolved clinical questions, and the practical implications for multidisciplinary care.