Simple SummaryThis meta-analysis examined the effect of general anesthetics on metastasis and recurrence after cancer surgery from clinical and pre-clinical studies. It showed that propofol-based total intravenous anesthesia is associated with lower risk of metastasis/recurrence and lower IL-6 level than inhalational anesthesia. Pre-clinical studies confirmed clinical observation and explored potential mechanisms.AbstractMetastasis or recurrence following curative surgery is the main indicator of tumor progress and is the main cause of patient death. For more than three decades, the potential for general anesthesia to affect cancer outcomes has been a subject of concern with considerable research interest. Here, we conducted this systematic review and meta-analysis to summarize the effect of inhalational anesthesia (IHNA) vs. propofol-based total intravenous anesthesia (TIVA) on metastasis and recurrence after cancer surgery from clinical and pre-clinical studies. The relative risk for metastasis/recurrence in TIVA is 0.61 (95% confidence interval (95% CI) 0.46 to 0.82,p= 0.0009) compared to IHNA. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery, thus we analyzed inflammatory cytokines levels after surgery under IHNA or TIVA. Based on pooled analysis, a lower IL-6 level was noticed in TIVA in comparison to IHNA (standardized mean difference (SMD) = 0.77, 95% CI = 0.097 to 1.44, I2= 92%,p= 0.02) but not TNF-α or IL-10. Preclinical animal model studies show that inhalational anesthetics increase the risk of breast cancer metastasis compared to propofol. In conclusion, the current evidence suggests intravenous anesthetic propofol is associated with less metastasis/recurrence and lower postoperative IL-6 level over inhaled anesthetics in the oncological surgery. We urge more well-designed clinical and preclinical studies in this field.