The efficacy and feasibility of neoadjuvant immunochemotherapy versus chemotherapy in Limited-Stage Small-Cell lung cancer.

BACKGROUND: The efficacy of neoadjuvant immunochemotherapy (NIC) in limited-stage small-cell lung cancer (LS-SCLC) remains undefined. This study aimed to evaluate the pathological and survival outcomes of NIC versus neoadjuvant chemotherapy (NC) and to compare NIC with upfront surgery in a real-world setting. MATERIALS AND METHODS: Patients with LS-SCLC (stage I-IIIB) who underwent upfront surgery or neoadjuvant treatment followed by radical surgery between February 2005 and November 2025 were retrospectively enrolled. Propensity score matching (PSM) (1:2) was used to compare the survival outcomes between the neoadjuvant and upfront surgery cohorts. The primary endpoint was pathological complete response (pCR) rate and major pathological response (MPR) rate. RESULTS: Among 164 included patients, 45 received neoadjuvant therapy (25 NIC, 20 NC). The NIC group achieved significantly higher pCR (52.0% vs. 5.0%; OR 19.31, p < 0.001) and major pathological response (MPR; 76.0% vs. 15.0%; OR 16.47, p < 0.001) rates compared to NC. Rates of pathological TNM and nodal downstaging were also superior with NIC. Surgical safety was comparable between NIC and NC. Within the neoadjuvant cohort, achieving pCR or MPR was associated with significantly improved disease-free survival (DFS). After PSM adjustment, the NIC group demonstrated significantly better DFS compared to the upfront surgery group (log-rank p = 0.007), with a trend toward improved overall survival. CONCLUSIONS: In LS-SCLC, NIC induces significantly deeper pathological responses than NC, translating into a promising DFS advantage over upfront surgery. pCR/MPR are strong prognostic surrogates. These findings support the therapeutic potential of surgery following NIC and warrant validation in prospective trials.