The Interplay of Preoperative Sarcopenia, Systemic Inflammation, and Neoadjuvant Therapy in Resectable...

Preoperative sarcopenia has emerged as an important determinant of adverse postoperative and long-term outcomes in patients with resectable non-small cell lung cancer (NSCLC). Its frequent coexistence with systemic inflammation may further worsen survival outcomes. At the same time, neoadjuvant chemotherapy and chemoimmunotherapy have substantially improved pathological response and survival in resectable NSCLC. However, their interaction with host-related factors such as sarcopenia and systemic inflammatory status remains insufficiently characterized. This narrative review aims to synthesize current evidence regarding the interplay between preoperative sarcopenia, systemic inflammation, and neoadjuvant therapy in resectable NSCLC and evaluates their potential combined impact on surgical and oncological outcomes. A narrative synthesis of 20 studies involving patients undergoing lung cancer resection was performed. Sarcopenia was primarily assessed using computed tomography or PET-CT-derived skeletal muscle indices, most commonly the skeletal muscle index, whereas systemic inflammation was evaluated using biochemical inflammatory markers. The available evidence consistently indicates that preoperative sarcopenia is associated with poorer long-term survival, and this adverse effect appears to be amplified in the presence of systemic inflammation. Although neoadjuvant chemoimmunotherapy has improved tumor response and survival outcomes, it may also act as a systemic stressor capable of aggravating muscle loss. Importantly, no study to date has simultaneously evaluated sarcopenia, systemic inflammation, and neoadjuvant therapy within a unified analytical framework. Most available studies focus primarily on sarcopenia, while inflammatory or treatment-related parameters are typically analyzed separately. Overall, while sarcopenia and systemic inflammation are recognized predictors of adverse outcomes in resectable NSCLC, robust evidence integrating them with neoadjuvant therapy is lacking. Clarifying their potential interaction may improve risk stratification and help to optimize perioperative management strategies in the era of neoadjuvant therapy.