Perioperative Antifibrotic Treatment and Early Postoperative Outcomes in Patients With Idiopathic Pulmonary Fibrosis Undergoing Lung Cancer Surgery: A Systematic Review and Meta‐Analysis

ABSTRACT

Patients with idiopathic pulmonary fibrosis (IPF) undergoing lung cancer surgery are at high risk of acute exacerbation of IPF (AE‐IPF), which is associated with high mortality. Although antifibrotic therapy (AFT) has been proposed as a preventive strategy, evidence remains limited and heterogeneous, particularly regarding early postoperative outcomes. We systematically searched major databases, including PubMed and Ichushi‐Web, through August 2025 to evaluate perioperative AFT in patients with IPF undergoing surgery. Eligible studies reported postoperative AE‐IPF or mortality within 30–90 days. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using common‐ and random‐effects models. Five retrospective cohort studies predominantly evaluating pirfenidone were included. AFT was associated with a lower incidence of postoperative AE‐IPF both within 30 days (RR, 0.24; 95% CI, 0.07–0.76; I ²  = 0%) and 90 days (RR, 0.23; 95% CI, 0.09–0.57; I ²  = 0%). AFT was associated with lower mortality at 30 days (RR, 0.12; 95% CI, 0.02–0.91; I ²  = 0%) and 90 days (RR, 0.13; 95% CI, 0.02–0.76; I ²  = 0%). Sensitivity analyses, including a nationwide database study, supported the association, although the effect was attenuated. Evidence for nintedanib was limited to a small case series. Perioperative AFT, particularly with pirfenidone, was associated with lower rates of AE‐IPF and mortality, including within 30 days post‐lung cancer surgery. These findings underscore the clinical relevance of early postoperative outcomes and support further prospective studies to clarify the role of perioperative AFT.