Abstract
BACKGROUND: The systemic immune-inflammation index (SII) has shown prognostic value in cancers, but its dynamic perioperative changes and implications in non-small cell lung cancer (NSCLC) remain underexplored. This study investigates the prognostic significance of perioperative SII changing patterns in resectable stage I-III NSCLC. METHODS: A retrospective cohort of 2,489 patients undergoing curative resection for stage I-III NSCLC [2013-2018] was analyzed. SII (neutrophils × platelets/lymphocytes) was measured preoperatively, postoperatively, and serially over 12 months. Restricted cubic splines (RCS) and X-tile determined optimal SII cutoffs. Latent class growth mixed models (LCGMMs) identified longitudinal SII trajectories. Associations with recurrence-free survival (RFS) and overall survival (OS) were evaluated using Cox models. RESULTS: High preoperative SII (>50.4), elevated postoperative/preoperative SII ratio (>2.3), and persistent postoperative SII elevation independently predicted worse RFS [adjusted hazard ratios (HRs): 1.37, 1.76, and 2.46, respectively; all P<0.05]. Three distinct SII trajectories emerged: slow-decreasing (93.7%, 3-year RFS 74.4%), sharp-decreasing (4.0%, 3-year RFS 42.0%), and rising (2.31%, 3-year RFS 43.2%). The rising trajectory group exhibited bimodal SII peaks at 2-3 and 8-12 months postoperatively, correlating with a 2.46-fold increased recurrence risk [95% confidence interval (CI): 1.50-4.03; P<0.001] compared to the slow-decreasing group, even after adjusting for preoperative SII and clinicopathological factors. CONCLUSIONS: Perioperative SII changing patterns provide critical prognostic insights beyond static measurements and demonstrate potential for predicting postoperative recurrence risk in stage I-III NSCLC patients.