Immune checkpoint inhibitors before lung cancer surgery show acceptable safety profile

INTRODUCTION: The integration of immune checkpoint inhibitors (ICIs) into the management of resectable non-small cell lung cancer (NSCLC) has markedly improved pathological response and survival. However, the effect of ICI-based regimens on surgical feasibility, complexity, and perioperative safety remains uncertain. This study aimed to systematically evaluate surgical outcomes following neoadjuvant or perioperative ICI-based therapy, with or without chemotherapy. METHODS: A systematic search of PubMed, EMBASE, Scopus, Cochrane CENTRAL, and Web of Science was conducted from database inception to January 2025 according to PRISMA guidelines. Only prospective single-arm and randomized controlled trials reporting surgical outcomes after ICI-based regimens in resectable NSCLC were included. Pooled event proportions (EP) were estimated using random-effects meta-analysis with Freeman-Tukey transformation. Meta-regression analyses compared chemo-immunotherapy (CTIO) versus immunotherapy-only (IO) protocols. RESULTS: Twenty-seven eligible trials comprising 2691 patients were analyzed. The pooled EP for intraoperative complications was 0.03, postoperative complications 0.27, and postoperative mortality 0.01. Pneumonectomy was performed in 10% of cases. Minimally invasive surgery (MIS) was used in 47% of resections, with a 20% conversion rate and 9% surgical delays. Meta-regression revealed higher intraoperative complications and surgery omission with CTIO protocols, while IO regimens showed higher postoperative mortality. No significant differences were found in pneumonectomy rate, MIS utilization, or conversion. CONCLUSIONS: Surgery following ICI-based therapy is feasible and safe in appropriately selected patients but presents distinct perioperative challenges. Differing risk profiles between treatments underscore the need for multidisciplinary coordination, experienced thoracic surgeons, and treatment centralization in resectable NSCLC within the immunotherapy era.