Salvage Surgery Following Systemic Therapy in Initially Unresectable Non‐Small Cell Lung Cancer

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BACKGROUND: This study evaluated the safety, long-term survival, and prognostic factors associated with salvage pulmonary surgery following systemic therapy for initially unresectable non-small cell lung cancer (NSCLC). METHODS: Between 2014 and 2024, this single-center retrospective review identified 32 patients (median age: 61.0 years) with NSCLC initially considered unresectable who subsequently underwent curative-intent pulmonary resection after chemotherapy, targeted therapy, and/or immunotherapy. The primary endpoint was overall survival (OS); secondary endpoints included recurrence-free survival (RFS), major morbidity (Clavien-Dindo grade ≥ IIIa), and R0 resection rate. The Kaplan-Meier method and log-rank test were employed. RESULTS: Reasons for unresectability at initial diagnosis were distant metastasis (n = 20; 62.5%), N3 nodal disease (n = 6; 18.8%), bulky N2 nodal disease (n = 3; 9.4%), and tumor or nodal extension requiring pneumonectomy (n = 3; 9.4%). Overall, 65.6% patients underwent lobectomy, with R0 resection achieved in 81.3% and pathological complete or major response observed in 15.6%. Overall complication and major morbidity rates were 12.5% and 3.1%, respectively; no 90-day mortality was observed. After a median follow-up of 40.1 months, median OS was not reached, whereas median RFS was 49.9 months; 5-year OS and RFS were 75.0% (95% CI 51.6-88.3) and 46.3% (95% CI 26.3-64.2), respectively. Notably, adenocarcinoma histology was significantly more prevalent in the good-prognosis group (88.9% vs. 35.7%, p = 0.003). CONCLUSIONS: Salvage pulmonary surgery following systemic therapy is safe, yielding a 5-year OS rate of 75% in carefully selected patients with advanced NSCLC. Prevalent adenocarcinoma histology in the good-prognosis cohort is associated with superior outcomes.

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