The Impact of Anesthesia on Cancer Recurrence and Postoperative Cognition
Cancer remains one of the leading causes of premature mortality worldwide, with global incidence and mortality projected to rise dramatically over the coming decades. After surgical intervention for cancer, surgical trauma, physiological stress, and immune suppression may influence both immediate postoperative recovery and long-term cancer outcomes. The selected anesthesia regimen also impacts outcomes, as different anesthetic agents exhibit varying immunomodulatory and inflammatory effects1 that may influence tumor progression, cancer recurrence, and the quality of postoperative recovery, particularly regarding cognition. Consequently, choosing the right anesthetic agents has become an area of increasing interest in oncologic anesthesia research and underscores the importance of individualized anesthetic strategies in cancer surgery.2
Propofol is one of the most widely used anesthetic agents due to its rapid onset, short duration of action, and recovery profile.3 Beyond its primary anesthetic action through modulation of gamma-aminobutyric acid (GABAA) receptors, propofol also affects NMDA receptors and voltage-gated ion channels, contributing to systemic benefits. Increasing evidence suggests that propofol also possesses immunomodulatory and anti-tumor properties. Preclinical studies across several cancer cell lines (including lung, colorectal, and pancreatic cancers) have demonstrated that propofol can suppress tumor growth, migration, and/or proliferation through metabolic disruption, regulation of microRNAs, and modulation of key signaling pathways. For example, propofol suppressed small cell lung cancer growth and promoted apoptosis through the microRNA-21 signaling pathway in a murine model of non-small cell lung cancer (NSCLC).4 These findings suggest that propofol-based anesthesia may improve oncologic outcomes by potentially reducing cancer recurrence.
Volatile inhaled anesthetics, including sevoflurane, isoflurane, desflurane, and halothane, are widely used for both induction and maintenance of anesthesia due to their ease of administration and reliable clinical effects. Some in vitro studies suggest agents like sevoflurane may inhibit tumor cell proliferation, induce apoptosis, and increase chemosensitivity. In particular, a study on colon cancer cells demonstrated sevoflurane inhibited cell proliferation, induced apoptosis, and regulated the epithelial-mesenchymal transition through the extracellular signal-regulated kinase (ERK) signaling pathway.5 However, other studies provide evidence for the anesthetic’s more detrimental effects: for example, sevoflurane was found to promote cell proliferation, migration, and invasion through PI3K/AKT signaling in cervical cancer cells.6 These conflicting findings highlight the complex links between volatile anesthetics in cancer progression and outcomes.
Propofol and volatile anesthetics may influence the development of postoperative cognitive dysfunction (POCD) through differing effects on neuroinflammation, neuronal signaling, and neurotoxicity. Propofol-based total intravenous anesthesia (TIVA) has been proposed to reduce the risk of early POCD by attenuating neuroinflammatory responses and limiting amyloid-β–related neurotoxicity, which may help preserve cognitive function after surgery. In addition, randomized controlled trials have reported lower rates of early POCD and postoperative delirium in patients receiving propofol compared to volatile agents, particularly among older adults undergoing major cancer or cardiac procedures.7 These findings suggest that propofol’s anti-inflammatory and neuroprotective properties may contribute to improved early postoperative cognitive outcomes.
In contrast, volatile anesthetics have been associated in some studies with greater neuroinflammation and transient impairment in early postoperative cognitive recovery. However, the evidence remains inconsistent. While some trials demonstrate increased early POCD incidence with volatile agents compared with propofol,7 other studies report no significant differences in cognitive outcomes between anesthetic types.8
Accumulating evidence suggests that the approach to anesthesia during cancer surgery may influence both tumor recurrence and postoperative cognition through distinct immunological and neuroinflammatory mechanisms, with propofol demonstrating potential benefits for patient outcomes. However, inconsistent findings across experimental and clinical studies highlight the need for further research to clarify the long-term oncologic and cognitive effects of propofol and volatile anesthetics, as well as how to guide optimal anesthetic strategies for cancer patients.
References
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2. Jin IH, Lew MW. The Impact of Total Intravenous Anesthesia and Volatile Anesthetics on Minimizing Cancer Recurrence and Postoperative Cognition. Cureus. 2025;17(7):e87379. https://doi.org/10.7759/cureus.87379
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6. Zhang W, Sheng B, Chen S, et al. Sevoflurane Enhances Proliferation, Metastatic Potential of Cervical Cancer Cells via the Histone Deacetylase 6 Modulation In Vitro. Anesthesiology. 2020;132(6):1469-1481. https://doi.org/10.1097/aln.0000000000003129
7. Varsha AV, Unnikrishnan KP, Babu S, PR Suneel, Thomas K. Comparison of Propofol-based TIVA vs Volatile Anaesthesia with Sevoflurane for Post Operative Delirium in Adult Coronary Artery Bypass Grafting Surgery: Prospective Randomized Single Blinded Study. Journal of cardiothoracic and vascular anesthesia. Published online May 1, 2024. https://doi.org/10.1053/j.jvca.2024.05.027
8. Guo L, Lin F, Dai H, et al. Impact of Sevoflurane Versus Propofol Anesthesia on Post-Operative Cognitive Dysfunction in Elderly Cancer Patients: A Double-Blinded Randomized Controlled Trial. Medical Science Monitor. 2020;26. https://doi.org/10.12659/msm.919293