The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies

Wan-Kun Chen, Chang-Hong Miao, Wan-Kun Chen, Chang-Hong Miao

Abstract

Animal models have shown that regional anesthesia (combined with or without general anesthesia) would attenuate the surgical stress response by preserving immune function and result in better long-term outcome. In order to test the hypothesis that cancer patients who had surgery with epidural anesthesia (EA) would have better outcome (either overall survival [OS] or recurrence-free survival [RFS]) than those who were general anesthesia (GA), we performed this meta-analysis. By searching relevant literature, a total of 14 studies containing 18 sub-studies (seven in OS analysis and eleven in RFS analysis) were identified and meta-analyzed. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the strength of association. For OS, the random-effects model was used to analyze the data and demonstrated an OS benefit in favor of EA compared with GA alone (HR = 0.84, 95% CI 0.74-0.96, P = 0.013). The influence analysis showed the robustness of the results. Specifically, a significantly positive association between EA and improved OS was observed in colorectal cancer (HR = 0.65, 95% CI 0.43-0.99, P = 0.045). For RFS, the random-effects model was used to analyze the data and no significant relationship between RFS benefit and EA (HR = 0.88, 95% CI 0.64-1.22, P = 0.457) was detected. In conclusion, our meta-analysis suggests that epidural anesthesia and/or analgesia might be associated with improved overall survival in patients with operable cancer undergoing surgery (especially in colorectal cancer), but it does not support an association between epidural anesthesia and cancer control. Prospective studies are needed to determine whether the association between epidural use and survival is causative.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. PRISMA flowchart.
Figure 1. PRISMA flowchart.
EA, epidural anesthesia; GA, general anesthesia.
Figure 2. Forest plot and influence analysis…
Figure 2. Forest plot and influence analysis of meta-analysis.
In figure 2A (for overall survival analysis) and 2C (for recurrence-free survival analysis), each study is shown by the point estimate of the hazard ratio (HR) (the size of the square is proportional to the weight of each study) and 95% confidence intervals (CIs) for the HR (extending lines). Figure 2B and 2D show the influence of individual studies on the summary HR. The vertical axis indicates the overall HR and the two vertical axes indicate its 95% CIs. Every hollow round indicates the pooled HR when the left study is omitted in this meta-analysis. The two ends of every broken line represent the respective 95% CIs.
Figure 3. Publication bias plots.
Figure 3. Publication bias plots.
Figure 3A and 3B show the Begg’s funnel plots of studies included in the meta-analysis for overall survival and recurrence-free survival, respectively. The vertical axis represents log [HR] and the horizontal axis means the standard error of log [HR]. Horizontal line and sloping lines in funnel plot represent summary HR and expected 95% CIs for a given standard error, respectively. Area of each circle represents contribution of the study to the pooled OR.

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