Real-world outcomes and prognostic risk stratification of neoadjuvant immunotherapy for stage III lung squamous cell carcinoma.

8047 Background: While neoadjuvant immunotherapy (nIO) is the standard of care for resectable NSCLC, its efficacy in "potentially resectable" (PR) stage III lung squamous cell carcinoma (LUSC)—specifically patients with T4 invasion or multi-station N2 disease—remains underrepresented in clinical trials. We evaluated whether nIO could facilitate surgical conversion in PR patients comparable to initially resectable (IR) candidates and constructed a multidimensional risk stratification system to optimize decision-making. Methods: We retrospectively analyzed patients with stage III LUSC treated with neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy (January 2019–December 2024). The cohort was stratified into IR and PR groups, with PR defined by complex anatomy (T4 invasion or multi-station N2). Endpoints included surgical conversion, major pathological response (MPR), disease-free survival (DFS), and overall survival (OS). Baseline predictors were identified via logistic regression. A pathological risk score (pRS) was developed using Cox regression based on independent risk factors for DFS in the R0 resection cohort. Results: Of 210 evaluable patients, 170 (81.0%) underwent surgery with a 96.5% R0 resection rate. The PR cohort (n = 128) achieved surgical conversion rates comparable to the IR cohort (n = 82) (82.9% vs. 90.7%; P = .19). Notably, PR patients demonstrated superior nodal downstaging (74.5% vs. 58.8%; P = .047) compared with IR patients. Long-term survival outcomes showed no statistically significant difference between PR and IR groups (DFS: HR, 1.25; 95% CI, 0.77-2.04; OS: HR, 1.41; 95% CI, 0.76-2.62). Multivariable analysis identified baseline NLR ≥ 2.75 and CYFRA 21-1 ≥ 6.0 ng/mL as independent predictors of poor therapeutic benefit. The constructed pRS system (integrating non-MPR status, vascular, and pleural invasion) effectively stratified postoperative recurrence risk (P < .0001; 1-year AUC, 0.73). Analysis of treatment failure (n = 40) revealed that baseline fibrinogen > 3.5 g/L was associated with disease progression, while grade 3–5 pneumonitis was a primary cause of surgical dropout in patients with high PD-L1 expression. Conclusions: In this real-world cohort, nIO facilitated high R0 resection rates in complex stage III LUSC, allowing potentially resectable patients to achieve survival outcomes equivalent to initially resectable candidates. Nodal clearance appears to be a key driver of benefit in the PR subgroup. The novel pRS system and biomarkers (NLR, CYFRA 21-1, fibrinogen) provide a robust framework for patient selection and postoperative management.