In Reply
This letter is in response to the letter by Dr. Milian, who argues that it is difficult to accept a mortality benefit from such level of anesthetic selection effect in our paper.1 Additionally, he states that propensity scores are associated with confounding in observational trials.
We agree that the magnitude of the anesthetic selection effect that we observed is considerably larger than in previous studies. A large retrospective analysis found a 30% lower death rate with the use of propofol anesthesia than with the use of sevoflurane or isoflurane in patients receiving surgical treatment for a solid tumor.2 Similarly, Enlund et al.3 reported a 25% lower death rate with propofol anesthesia than with sevoflurane in patients receiving colon cancer surgery. And we found a 65% lower death rate with propofol anesthesia than with desflurane anesthesia in patients receiving colon cancer surgery. This finding might result from the fact that we used more sophisticated statistics, larger sample size, and desflurane (but not sevoflurane or isoflurane).
In vitro and animal data support an important effect of anesthetic selection on cancer growth and survival. Furthermore, some previous retrospective analyses have suggested that there may be a clinically important effect in humans. Our results are consistent with the results of previous studies of propofol-based anesthesia that reported better outcomes after esophageal, gastric, or colon cancer, compared with volatile anesthetics.3–5 In addition, Sessler and Riedel6 also concluded that propofol-based anesthesia provided better outcomes after major surgery for gastrointestinal cancers (such as esophageal, or gastric, or colon cancer), but not breast cancer, compared with volatile anesthetics. That might be attributable to breast cancer patients having minor surgeries, and the degree of biologic perturbation depends on the magnitude of the surgical insult.6
It seems biologically implausible that something as complicated as cancer can be reduced by more than a factor-of-two simply by anesthetic selection. Furthermore, almost surely our results overestimate the true treatment effect, which is common in retrospective studies. Nonetheless, our results are at least consistent in direction and indicate that further work, especially randomized trials, should be pursued. Besides, the major problem in our retrospective study is that both groups of patients are severely imbalanced (i.e., age and tumor-node-metastasis), and we have tried our best to conduct a propensity score matching to deal with this issue.
Although Dr. Milian states that propensity scores are associated with confounding in observational trials, but we have applied two adjustment approaches, namely propensity score modeling and matching, to avoid potential confounding effects.7,8 Furthermore, all standardized mean differences for the variables are less than 0.1, which is usually interpreted as evidence that groups are matched well. Finally, we have mentioned that we still cannot avoid the possibility of residual confounding attributable to unmeasured confounders in the limitations in our published article.1
To the best of our knowledge, propofol anesthesia might be associated with better survival in patients who underwent major gastrointestinal cancer surgeries, but not minor surgeries.6 Prospective studies are warranted to evaluate the effects of propofol anesthesia on the surgical outcomes of cancer patients.
Competing Interests
The authors declare no competing interests.