Perioperative antifibrotic therapy for patients with idiopathic pulmonary fibrosis undergoing lung cancer surgery: A systematic review and meta-analysis.

Background: Patients with idiopathic pulmonary fibrosis (IPF) undergoing lung cancer surgery face a 4.4-20 % risk of acute exacerbation (AE-IPF) with mortality exceeding 50 %. The potential role of perioperative antifibrotic therapy in reducing surgical complications in this high-risk population remains unclear.

Objectives: To evaluate whether perioperative antifibrotic therapy (pirfenidone/nintedanib) reduces complications, particularly acute exacerbations and mortality, in IPF patients undergoing lung cancer surgery through systematic review and meta-analysis.

Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of observational studies examining perioperative antifibrotic therapy in IPF patients undergoing lung cancer surgery. Four studies comprising 261 patients (124 treated, 137 controls) from Japan and Italy (2016-2024) were analyzed. Pooled risk ratios were calculated using Review Manager 5.4. The study protocol was registered with PROSPERO (ID: CRD42025649005).

Results: Perioperative antifibrotic therapy achieved a 69 % reduction in AE-IPF risk (RR 0.31, 95 % CI 0.13-0.70) and an 81 % reduction in 90-day mortality (RR 0.19, 95 % CI 0.07-0.52). Additional benefits included significantly shorter hospital stays (5 vs 7 days, p = 0.029) and reduced complications, including decreased prolonged air leak rates (3.4 % vs 26.9 %). Adverse events were minimal, consisting primarily of mild nausea and photosensitivity.

Conclusions: Perioperative antifibrotic therapy significantly reduces acute exacerbations and mortality in IPF patients undergoing lung cancer surgery. However, findings are limited by small observational studies concentrated in specific geographic regions. Randomized controlled trials are needed to confirm efficacy and establish standardized treatment protocols.