Anesthesia and Long-term Oncological Outcomes

A Systematic Review and Meta-analysis

Chun-Yu Chang, MD; Meng-Yu Wu, MD; Yung-Jiun Chien, MD; I-Min Su, MD; Shih-Ching Wang, MD; Ming-Chang Kao, MD, PhD

Disclosures

Anesth Analg. 2021;132(3):623-634. 

In This Article

Abstract and Introduction

Abstract

Background: Whether propofol elicits a survival benefit over volatile anesthetics during cancer surgery remains inconclusive. The primary aim of this systematic review and meta-analysis is to compare the effects of propofol-based total intravenous anesthesia (TIVA) with any volatile anesthesia on long-term oncological outcomes. The secondary aim is to compare propofol-based TIVA with specific volatile agents on long-term oncological outcomes.

Methods: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library from inception through March 3, 2020. Randomized control trials and observational studies that compared the effects of propofol-based TIVA and volatile anesthesia on long-term oncological outcomes, which also reported hazard ratios (HR) as effect estimates, were considered eligible for inclusion. Using the inverse variance method with a random-effects model, HR and 95% confidence intervals (CI) were calculated. Trial sequential analysis was incorporated to test if the results were subject to a type I or type II error.

Results: Nineteen retrospective observational studies were included. Patients who received propofol-based TIVA during cancer surgery were associated with significantly better overall survival than those who received volatile anesthesia (HR = 0.79, 95% CI, 0.66–0.94, P = .008, I 2 = 82%). In contrast, no statistically significant difference was observed in recurrence-free survival between patients who received propofol-based TIVA and volatile anesthesia during cancer surgery (HR = 0.81, 95% CI, 0.61–1.07, P = .137, I 2 = 85%). In the subgroup analysis by different volatile anesthetics, patients who received propofol-based TIVA were associated with better overall survival than those who received desflurane (HR = 0.54, 95% CI, 0.36–0.80, P = .003, I 2 = 80%). In contrast, there was no statistically significant difference in overall survival between patients who received propofol-based TIVA and those who received sevoflurane (HR = 0.92, 95% CI, 0.74–1.14, P = .439, I 2 = 70%). In the trial sequential analysis of overall survival, the cumulative Z curve reached the required heterogeneity-adjusted information size and crossed the traditional significance boundary. In contrast, in the trial sequential analysis of recurrence-free survival, the cumulative Z curve did not cross the traditional significance boundary. However, the required heterogeneity-adjusted information size has not yet been reached.

Conclusions: Propofol-based TIVA is generally associated with better overall survival than volatile anesthesia during cancer surgery. Further large-scaled, high-quality randomized control trials are warranted to confirm our findings.

Introduction

Cancer remains the leading cause of death globally, accounting for an estimated 9.6 million deaths in 2018.[1] Despite the medical advances in surgical techniques, as well as neoadjuvant and adjuvant therapies accompanying surgery, many patients still suffer from a recurrence of cancer after surgery and curative treatment. The perioperative window has been known to influence cancer recurrence and may have an impact on the long-term survival of patients with cancer.[2] Surgery itself increases the risks of micrometastasis and the formation of new metastatic foci due to the shedding of tumor cells into the circulatory system, as well as the activation of the hypothalamic–pituitary–adrenal axis and the release of adrenaline, cortisol, and proinflammatory mediators caused by profound surgical stress and tissue damage.[3,4] Recent studies suggest that the choice of anesthetic techniques during cancer surgery, that is, propofol-based total intravenous anesthesia (TIVA) versus volatile anesthesia, may play an important role in this regard.[5–7]

Volatile anesthetics and intravenous propofol have distinct influences on both cancer cell biology and host immunity. Several in vitro studies have demonstrated that the exposure of tumor cells to volatile anesthetics is associated with an increased expression of prometastatic and protumorigenic factors via signaling pathways including hypoxia-inducible factor-1α and transforming growth factor-β/Smad.[8–10] These factors promote angiogenesis, tumor cell proliferation, migration, and invasion. In contrast, propofol has been shown to suppress the isoflurane-induced upregulation of hypoxia-inducible factor-1α,[10] and inhibit proliferation, migration, and invasion of tumor cells.[11] In addition, it has been postulated that volatile anesthetics can suppress both innate and adaptive immunity,[12] especially the natural killer cells, while propofol has been reported to preserve host immunity.[13] This notion has been supported by recent literature that reports the potential benefit of propofol-based TIVA over volatile anesthesia in overall survival, but not recurrence-free survival, of patients having cancer surgery.[14,15]

While awaiting the results of the ongoing prospective randomized control trials,[16–21] several retrospective cohort studies have been published to address this issue, yet the results are conflicting and inconclusive. To investigate the most recent studies with regard to the effects of propofol-based TIVA and volatile anesthesia on long-term oncological outcomes, we conducted an updated meta-analysis in the hope of providing further evidence for clinical practice.

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