Abstract
Background/Objectives: Lidocaine has demonstrated immunomodulatory properties and promising antitumor effects in experimental models, but its impact on long-term outcomes following oncologic surgery remains unclear. This study aimed to compare the impact of intraoperative lidocaine versus remifentanil on long-term cancer outcomes after primary lung cancer surgery. Methods: This is a post hoc analysis of a randomized controlled trial (NCT03905837, EudraCT 2016-004271-52). From 154 patients who underwent elective lung resection via video-assisted thoracoscopic surgery (VATS) between January 2019 and June 2021 and were randomized to receive intraoperative lidocaine (intravenous or paravertebral) or remifentanil, we analyzed data from patients with confirmed primary lung cancer in the surgery specimen. Overall survival (OS) and disease-free survival (DFS) were assessed through May 2025. Survival outcomes were analyzed using Kaplan-Meier curves and log-rank tests. A multivariate Cox proportional hazards model was used to adjust for potential confounders. Results: Among the 97 patients with primary lung cancer finally included in the analysis, those in the lidocaine group exhibited improved OS compared with those who received intravenous remifentanil (log-rank p = 0.022). This association remained significant in the multivariate Cox regression analysis (HR 2.59, 95% CI 1.13-5.96, p = 0.025). No significant differences were observed in DFS overall (log-rank p = 0.283) or in DFS limited to recurrences of cancers present at the time of surgery, either the resected primary tumor or a prior malignancy (log-rank p = 0.080). Conclusions: In this post hoc analysis, lidocaine administration during oncologic lung resection was associated with improved OS in primary lung cancer patients. No differences in DFS were observed between groups; however, a non-significant trend toward improved DFS in lidocaine patients was noted when focusing on recurrences of cancers present at the time of surgery. Further investigation in larger prospective studies is warranted.