Integrating Surgery and Radiotherapy Following Tislelizumab-based Conversion Therapy in N3-Stage III NSCLC

This is a prospective, multicenter, single arm phase 2 clinical trial enrolling 30 newly diagnosed stage III NSCLC patients with N3 lymph-node metastasis (T1-4N3M0, AJCC 9th edition). Mainly eligible patients must be negative for sensitive gene muta-tions, treatment-naive for systemic or local therapy, aged ≥18 years, and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with at least one measurable lesion according to RECIST 1.1 criteria at baseline. Key exclu-sion criteria include invasion of critical structures such as the aorta, trachea, esopha-gus, or heart by the primary tumor or metastatic lymph nodes, as well as the presence of Pancoast tumors. Following induction therapy with 3-4 cycles of Tislelizumab combined with platinum-based chemotherapy, patients without disease progression will be evaluated by a multidisciplinary team (MDT) and assigned to treatment strategies based on eligibility and patient preference. Patients deemed eligible to surgery will receive standard lung cancer resection (excluding total pneumonectomy), including removal of the primary tumor, ipsilateral hilar, and ipsilateral mediastinal lymph nodes, followed by hypofractionated chemoradiotherapy targeting N3 meta-static lymph nodes. Patients ineligible for or unwilling to undergo surgery will re-ceive definitive conventional CRT. After completion of local treatment, all patients will continue Tislelizumab maintenance therapy until radiographic disease progres-sion, unacceptable toxicity, or completion of one year of treatment. The primary endpoint is the 1-year event-free survival rate (1y-EFS rate). Secondary endpoints include EFS, overall survival (OS), surgical conversion rate, time to distant metasta-sis (TTDM), time to local recurrence (TTLR), adverse events (AEs), and the impact of the integrated treatment approach on patient-reported outcomes (PROs). Explora-tory analyses will be conducted to identify predictive and prognostic biomarkers us-ing tumor tissue and blood samples collected at multiple time points during the study.