Anesthesia type during surgery for treatment of biologically aggressive cancers: Results of the GA-CARES randomized, multicenter trial.

Abstract

LBA1512 Background: Surgical resection is a widely used treatment for cancer. Patients can be “seeded” with their own cancer cells during surgery, with the immune response to these circulating cancer cells influencing recurrence risk. Numerous preclinical and retrospective studies have suggested that propofol-based anesthesia may be superior to volatile halogenated ethers with respect to cell-mediated immunity, implantation of circulating tumor cells and cancer-related outcomes. Due to the above, an expert Consensus panel called for large, randomized trials on this topic. Methods: To test the hypothesis that propofol-based anesthesia leads to better cancer-related outcomes, adults at five U.S. sites scheduled for resection of biologically aggressive malignancies from the pancreas, esophagus, lung, stomach, bile ducts, liver, bladder, or peritoneal surface were randomly assigned to receive either propofol or a volatile agent for maintenance of general anesthesia. Data sources included the National Death Index (gold standard for vital status in the US), NY Cancer Registry, and hospital electronic medical records. The primary and key secondary endpoints were overall survival and disease-free survival, respectively. Assuming a 5% absolute difference in 2-year overall survival rates (85% vs 90%) between study arms, power using a planned two-sided log-rank test with type I error of 0.05 (no planned interim analyses) was calculated to be 97.4% based on a target enrollment of 1,800 subjects (final n=1,826). Results: The study population was diverse with 41.6% females, 22.1% non-whites, and 6.0% Latinos. Most patients were over 65 years of age and were at higher risk for surgery with approximately 85% classified as ASA 3 or 4. Adherence to the study protocol was very high with 95.9% of patients receiving the assigned anesthetic drug exclusively. Through up to 60 months of follow-up (median 40, IQR 22-60 months), 708 (40.2%) patients died in the intent-to-treat (ITT) population (n=1763). In contrast to our hypothesis, propofol-treated patients did not exhibit better survival (propofol 359 deaths/881 [40.7%] vs. volatile 349 deaths/882 [39.6%]; hazard ratio 1.07; 95%CI 0.92-1.24; P=0.371). In the per-protocol population (n=1411), significantly more patients randomized to propofol died through the pre-specified 2-year follow-up (25.5% vs. 20%; hazard ratio 1.31; 95%CI 1.05-1.64; p=0.017). Results were similar for disease-free survival and were consistent across numerous prespecified subgroups. Conclusions: Our large, multicenter trial shows that propofol-based anesthesia is not effective at improving cancer-related outcomes in patients who undergo resection of biologically aggressive malignancies; paradoxically, its use might result in worse outcomes compared with volatile anesthesia. Clinical trial information: NCT03034096 .