Volatile Versus Propofol General Anesthesia and Long-term Survival After Breast Cancer Surgery

A National Registry Retrospective Cohort Study

Mats Enlund, M.D., Ph.D.; Anders Berglund, Ph.D.; Anna Enlund, M.D.; Leif Bergkvist, M.D., Ph.D.


Anesthesiology. 2022;137(3):315-326. 

In This Article

Abstract and Introduction


Background: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge.

Methods: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance.

Results: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the breast cancer to be more advanced. Median follow-up was 33 months (interquartile range, 19 to 48). In the full, unmatched cohort, there was a statistically significantly higher overall survival among patients receiving propofol (13,489 of 13,873 [97.2%]) versus inhaled volatile (4,039 of 4,801 [84.1%]; hazard ratio, 0.80; 95% CI, 0.70 to 0.90; P < 0.001). After 1:1 propensity score matching (4,658 matched pairs), there was no statistically significant difference in overall survival (propofol 4,284 of 4,658 [92.0%]) versus inhaled volatile (4,288 of 4,658 [92.1%]; hazard ratio, 0.98; 95% CI, 0.85 to 1.13; P = 0.756).

Conclusions: Among patients undergoing breast cancer surgery under general anesthesia, no association was observed between the choice of propofol or an inhaled volatile maintenance and overall survival.


Retrospective cohort studies have shown that choice of a general anesthetic may be associated with survival after cancer surgery.[1–14] Biologically reasonable explanations are available.[15–22] The absolute magnitude of differences in long-term survival in these retrospective studies are comparable to the effects of chemotherapy, approximately five percentage points. However, there are three studies that focused on breast cancer alone, whereby no difference in survival could be observed between the agents.[23–25] Moreover, in the first two published retrospective studies, breast cancer was an exception from the overall results that indicated an association between the choice of anesthetic for cancer surgery and long-term survival (Timothy Wigmore, B.M., B.Ch., F.R.C.A., F.F.I.C.M., F.C.I.C.M., Department of Anesthesiology and Critical Care Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom, December 2019, written communication).[1,2] It is thus important to clarify the effects of anesthetics on long-term survival for patients with breast cancer. If there is no difference between anesthetic options, there would be no need to "switch" from the globally dominating volatile anesthetic technique to propofol and thereby no requirements for investment in infrastructure and staff training. If, on the other hand, a clinically significant difference between the techniques can be established for breast cancer, it may have major implications for the patients. A difference of five percentage points in survival, as indicated in retrospective studies, means that life is extended every year globally for about 80,000 patients.

A prospective, randomized, controlled trial, the "CAN Study," is underway.[26] Early follow-up data for breast cancer were recently presented, indicating no difference in survival between propofol and sevoflurane groups for patients with a minimum 1-yr follow-up (median follow-up, 2.7 yr).[27] As expected, mortality was low during this short period of time, which calls for caution in interpreting the results. Large retrospective studies offer a complementary evidence base to the very few randomized, controlled trials registered so far. We have recently conducted a relatively large retrospective study with data from seven Swedish hospitals on the association between survival after breast cancer surgery and choice of anesthetics.[28] A total of 6,305 patients with breast cancer were included. However, the main finding was an illustration of the weakness of retrospective design. The interpretation of the results was influenced by the methods for analysis. In the current article, we therefore used two Swedish national registries to incorporate more stable data on population level to reduce both sampling bias and selection bias. By merging these two population registries, we expected to get a data set with both low bias and, in addition, important demographic, anesthetic, surgical, and oncologic data to statistically adjust for known factors affecting survival. Based on some of the results analyzed,[1,2] we conservatively hypothesize that propofol-based anesthesia in patients undergoing breast cancer surgery is associated with five percentage points higher absolute survival rate compared with inhaled volatile-based anesthesia.