Comparison of Neoadjuvant Immunochemotherapy and Chemotherapy in Patients with Resectable Limited- Stage Small-Cell Lung Cancer: Outcomes, Adverse Events, Recurrence Profiles and Prognostic Markers

Abstract Background Limited-stage small-cell lung cancer (LS-SCLC) has a poor prognosis. While immune checkpoint inhibitors (ICIs) benefit extensive-stage disease, evidence on neoadjuvant ICI use in resectable LS-SCLC is scarce. This study compared neoadjuvant immunochemotherapy versus chemotherapy alone in this setting. Methods This retrospective study included 65 patients with resectable stage I–IIIB LS-SCLC. Twenty-one patients received neoadjuvant immunochemotherapy (nCI group: etoposide + platinum + ICI), and 44 received chemotherapy alone (nC group). Primary endpoints were pathological responses. Secondary endpoints included objective response rate (ORR), disease-free survival (DFS), overall survival (OS), safety, and surgical outcomes. Additionally, recurrence patterns and prognostic factors for DFS and OS were explored. Results The pathological complete response (pCR) rate was significantly higher in the nCI group (52.4% vs. 18.2%; P = 0.005). The major pathological response (MPR) rate was also higher (61.9% vs. 38.6%; P > 0.05). The nCI group showed favorable trends in ORR (90% vs. 68%), R0 resection (100% vs. 97.7%), median DFS (48.7 vs. 17.2 months; hazard ratio [HR] = 0.87, P = 0.69), and median OS (not reached vs. 41.6; HR = 0.43, P = 0.12). Grade 3–4 treatment-related adverse events (TrAEs) were comparable (38.1% vs. 31.8%). Recurrence patterns differed: nCI had more distant recurrence (72.7% vs. 25.8%), while nC had more local recurrence (18.2% vs. 51.6%). Non-pCR/non-MPR, postoperative pro-gastrin releasing peptide (Pro-GRP) positivity and Stage III were independent risk factors. Conclusions Neoadjuvant immunochemotherapy significantly improved pCR rates and showed promising survival trends in resectable LS-SCLC, with a manageable safety profile. It altered recurrence patterns and identified pathological response and Pro-GRP as key prognostic markers.