There has been ongoing debate about the relationship between cancer recurrence and anesthetic management. Therefore, the investigators will test the hypothesis that the recurrence free survival (RFS) after curative resection of NSCLC is higher in patient who received total intravenous anesthesia (TIVA) than volatile anesthetics in this multi-center randomized trials.

Surgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment which supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibits tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to retrospective observational nature of previous studies. Therefore, the investigators will test the hypothesis that the recurrence free survival (RFS) after curative resection of NSCLC is higher in patient who received TIVA than volatile anesthetics in this multi-center randomized trials.

This double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS group with a 1:1 ratio. A centralized, password-protected, and encrypted web-based electronic case report form will be used for randomization and data upload. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms.

The primary outcome will be recurrence free survival (RFS). Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years.

Confirmation of the study hypothesis would demonstrate that a relatively minor and low cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management.

Inclusion Criteria:

• American Society of Anesthesiologists physical status (ASA) Ⅰ-Ⅲ
• The Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Lung resection surgery (segmentectomy, lobectomy, bilobectomy, pneumonectomy; video-assisted, robot-assisted, or open) with curative intent for NSCLC (clinical Tumor, Node, Metastasis (TNM) stage Ⅰ- ⅢA).

Exclusion Criteria:

• Distant metastasis or malignant tumor in other organs that according to the attending surgeon is not in long-term remission
• Severe neurologic conditions
• Severe hepatic disease (Child-Pugh classification C)
• Renal failure requiring renal replacement therapy
• History of anesthesia and/or surgery within 1 yr
• Previous surgery due to lung cancer (except diagnostic biopsies)
• Contraindications to any study medication (history of allergy, hypersensitivity reaction, or any other contraindication)
• Planned joint extrapulmonary procedure
• Surgery under cardiopulmonary bypass or extracorporeal membrane oxygenation
• Postoperative sedation
• Pregnancy, or lactation
• Patient refusal.

Data sharing including the full protocol, individual participant and other relevant study data will be considered upon reasonable request. Only with the permission of the Data Review Board of Samsung Medical Center, the anonymized data will be available from the principal investigator (HJA).

within 3 years after publication

Data sharing including the full protocol, individual participant and other relevant study data will be considered upon reasonable request. Only with the permission of the Data Review Board of Samsung Medical Center, the anonymized data will be available from the principal investigator (HJA).