Anesthesia and Non-small Cell Lung Cancer Recurrence

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.