Induction chemo-immunotherapy followed by surgery or radiotherapy for locally-advanced III stage non-small cell lung cancer: prospective single center non-randomized study (preliminary results)

Abstract

Background. The evolving modalities of systemic treatment for non-small cell lung cancer (NSCLC) promotes the need to redefine different strategies for combined treatment in stage III and borderline-resectable lung cancer. Hereby we present the outcomes of a neoadjuvant chemo-immunotherapy regimen with subsequent individualized local control strategy of patients with locally advanced NSCLC. Materials. Prospective, single-center, non-randomized observational study enrolled patients with the following criteria: age > 18 years, histologically confirmed NSCLC without driver mutations (EGFR, ALK, ROS1), clinically staged as IIIA–IIIC per the 8th edition TNM classification, including cases deemed resectable and borderline-resectable, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. The protocol comprised 4 cycles of neoadjuvant chemo-immunotherapy following MDT-based definition of surgical resection or radiotherapy — based on a technical resectability and a risk of cardiopulmonary complications. Results. From September 2021 to October 2025, 119 patients were enrolled with male: female ratio 103:16 and median age 65 years (IQR, 59–69). Clinical stage distribution was: IIIA — 63 (52.9 %), IIIB — 51 (42.9 %), IIIC — 4 (3.4 %) and IIb — 1 (0.8 %). Histologically, adenocarcinoma and squamous cell carcinoma accounted for 41 (34.4 %) and 78 (65.6 %) cases respectively. The full course of neoadjuvant / induction therapy was completed by 109 (91.6 %) patients. Radiological response assessment by RECIST criteria revealed a partial (iPR), complete response (iCR) or stable disease (iSD) in 68 (57 %), 11 (9.2 %) and 35 (29.4 %) cases respectively. For local control 76 (63.9 %) patients underwent surgical resection and 26 (21.9 %) received radiotherapy. Postoperative complications (Clavien — Dindo classification) occurred in 11 of 76 surgical patients (14.5 %; 95 % CI, 8.3–24.1). A major pathological response (MPR) and complete response (pCR) were achieved in 21 (27.6 %) and 30 (39.5 %) cases respectively. Median overall survival (OS) and event-free survival (EFS) in the surgical cohort have not been reached, whereas in the radiotherapy group, median OS was 29 months (95 % CI, 17.3; not estimable) and median EFS was 15.5 months (95 % CI, 12.7; not estimable). Conclusion. Our findings support consideration of induction / neoadjuvant chemo-immunotherapy for selected cohort of patients with locally-advanced and borderline-resectable stage III NSCLC. Future investigations are needed to explore the benefits of proposed strategy.