Is there a room for radical salvage resection in initially-unresectable non-small cell lung cancer patients after EGFR-TKI based therapy?

Background: Tyrosine kinase inhibitors (TKIs) constitute the standard first-line systemic therapy for patients with unresectable epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Despite their initial efficacy, the majority of patients inevitably develop acquired resistance or experience local recurrence. This study aimed to evaluate the safety and feasibility of minimally invasive radical salvage surgery following TKI-based therapy in a cohort of patients with initially unresectable NSCLC. Methods: This retrospective single-center study evaluated patients who underwent radical salvage lung resection following TKI-based therapy. Surgical safety and short-term efficacy were assessed, and findings were compared with results from previously published studies. Results: Twenty-six patients underwent salvage surgery following first-line treatment with third-generation TKIs; 19 received TKI monotherapy, while seven received a combination of TKIs and chemotherapy. All patients underwent anatomical lung resection, with two cases requiring conversion to open thoracotomy. R0 resection was achieved in 96.2%. An R0 resection was achieved in 96.2% of cases. The median operative time was 145 minutes (range, 105-240 minutes), and the median intraoperative blood loss was 20 mL (range, 10-700 mL). Postoperative complications occurred in four patients (15.4%), including two major events in individuals who had received preoperative TKI therapy for more than 6 months. Compared to those with shorter treatment durations, patients with prolonged preoperative TKI exposure exhibited a longer postoperative hospital stay, although operative time, blood loss, and chest tube duration were comparable. Our perioperative outcomes were consistent with those reported in six prior retrospective studies. Conclusions: Radical salvage lung resection following TKI therapy is a feasible and safe option for carefully selected patients with initially unresectable EGFR-mutant NSCLC. This approach yields high rates of complete (R0) resection with acceptable morbidity. However, patients who have undergone extended preoperative TKI treatment may present with increased technical challenges and warrant meticulous perioperative planning.