Anesthesia Type during Cancer Surgery: Results of the GA-CARES Randomized, Multicenter Trial

Background: – Surgical resection is a widely used treatment for cancer. Patients can be “seeded” with their own cancer cells during surgery, and it has been postulated that the immune response to these circulating cancer cells can influence recurrence risk. Some preclinical and retrospective studies have suggested that propofol-based general anesthesia may be superior to volatile halogenated ethers with respect to cell-mediated immunity, implantation of circulating tumor cells, and cancer-related outcomes, but there are limited data from large randomized clinical trials. Methods: – The General Anesthetics in Cancer Resection (GA-CARES) trial is a multicenter, pragmatic, investigator-initiated, partially blinded, randomized superiority trial. Adults at five U.S. centers undergoing surgical resection of cancers associated with poor outcomes (pancreas, esophagus, lung, stomach, bile ducts, liver, bladder, or peritoneal surface) were randomized (1:1) to receive exclusive use of either propofol or volatile agent for maintenance of general anesthesia. The intent-to-treat population included all randomized patients (n = 1, 766) minus 3 patients who withdrew consent before surgery. The per-protocol population included patients completing surgery, with pathologically confirmed cancer, and receiving the assigned anesthetic drug. The primary endpoint was all-cause mortality (minimum 2-yr follow-up). Secondary endpoints included disease-free survival. Results: – Adherence to the protocol was high, with 95.9% of patients who had surgery receiving the assigned anesthetic exclusively. In contrast to the authors’ hypothesis, propofol-treated patients did not exhibit better survival (propofol 230 deaths out of 881 [26.1%] vs. volatile 202 deaths out of 882 [22.9%]; hazard ratio, 1.16; 95% CI, 0.96 to 1.41; P = 0.115 by exact stratified log rank test) in the intent-to-treat population (n = 1, 763). In the per-protocol population (n = 1, 411), significantly more patients randomized to propofol died through 2-yr follow-up (25.5% vs. 20%; hazard ratio, 1.31; 95% CI, 1.05 to 1.64; P = 0.017). Results were similar for disease-free survival (hazard ratio, 1.10; 95% CI, 0.9 to 1.36; P = 0.428) and were consistent across numerous subgroups. Conclusions: – Propofol-based anesthesia is not effective at improving cancer-related outcomes in patients undergoing resection of malignancies.