As the second leading cause of death in adults, cancer is a major global health concern.1 According to the American Cancer Society, an estimated 1.9 million new cancer cases were recorded in 2022 in the United States alone, with over 600,000 deaths from cancer.2 The current standard for cancer treatment involves surgery, radiotherapy, immunotherapy, and/or chemotherapy. Often, the elements of cancer treatment depend on the patient’s situation and the severity of the cancer. However, in emergent circumstances or other situations, immediate surgical excision may be necessary. Although surgery can be lifesaving for patients, it can increase the risk of micrometastasis due to disturbances in the tumor microenvironment, such as the shedding of tumor cells into the circulatory system, the activation of the hypothalamic–pituitary–adrenal (HPA) axis, and the release of pro-inflammatory mediators.3 Several studies have suggested that the anesthesia technique used during oncological surgery may play a role in post-operative outcomes, including overall survival and cancer recurrence.4,5
Volatile anesthesia and propofol have notably different effects on both cancer cell structure/functionality and host immunity, with potential long-term impacts on oncological outcomes. To date, there have been many research studies that demonstrate volatile anesthetics can increase expression of pro-metastatic and pro-tumorigenic factors such as hypoxia-inducible factor-1ɑ (HIF-1ɑ) and transforming growth factor-ꞵ.5 These factors are known to promote angiogenesis, tumor cell proliferation, invasion, chemoresistance, and migration. On the other hand, intravenous administration of propofol is associated with the inhibition of HIF-1ɑ,6 a master regulator of genes associated with initiating angiogenesis, apoptosis, and more. Increased expression of HIF-1ɑ is often an indicator of the development of embryonic vascularization, ischemic disease, and tumorigenesis.7 In 2014, researchers from London exposed human prostate cancer cells to either isoflurane, propofol, or both. HIF-1ɑ levels were experimentally increased through induction of hypoxia or treatment with cobalt chloride. Isoflurane assisted the hypoxia-induced upregulation of HIF-1ɑ, in addition to translocation from the cytoplasm to the nucleus. Here, the transcription factor can exert effects on downstream gene expression, ultimately resulting in cancer cell proliferation and migration.6 By contrast, cultures treated with propofol did not exhibit increased levels of HIF-1ɑ, despite artificial induction by the researchers. It was also found that propofol could prevent isoflurane-induced HIF-1ɑ activation and the resulting malignant effects.6
A 2021 meta-analysis compiled 19 retrospective observational studies and found that patients who received propofol anesthesia during oncological surgery had significantly better outcomes than those who received desflurane anesthesia. There was also a trend toward greater survival rates between patients who received propofol treatment and those who received sevoflurane/other volatile anesthetics; however, this difference was not statistically significant.5 When the researchers grouped the results by types of cancer, propofol treatment was associated with significantly better survival rates than volatile anesthesia for patients with gastroesophageal and hepatobiliary cancers, but not for patients with breast cancer, colorectal cancer, or glioma. Interestingly, there was no observed difference between propofol treatment and any type of volatile anesthesia administration in terms of recurrence-free survival.5
The choice of anesthesia approach during surgical procedures has significant implications for long-term oncological outcomes. The extant literature points toward a more beneficial impact of propofol anesthesia for use in cancer surgery, as opposed to volatile anesthetics. However, anesthesiologists must still consider patient-specific characteristics, including demographics and comorbidities, as well as cancer characteristics, such as type or severity of the tumor. As this field evolves, a tailored approach that accounts for both the anesthetic technique and the individual patient’s oncological profile will likely be crucial in optimizing long-term outcomes and enhancing overall cancer care.

References

1.Ahmad, Farida B., and Robert N. Anderson. “The Leading Causes of Death in the US for 2020.” JAMA, vol. 325, no. 18, May 2021, pp. 1829–30. https://doi.org/10.1001/jama.2021.5469
2.Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. “Cancer Statistics, 2022.” CA: a cancer journal for clinicians, 72(1), 2022
3.Dubowitz, Julia A., et al. “Implicating Anaesthesia and the Perioperative Period in Cancer Recurrence and Metastasis.” Clinical & Experimental Metastasis, vol. 35, no. 4, Apr. 2018, pp. 347–58. https://doi.org/10.1007/s10585-017-9862-x
4.Sessler, Daniel I., and Bernhard Riedel. “Anesthesia and Cancer Recurrence.” Anesthesiology, vol. 130, no. 1, Jan. 2019, pp. 3–5. https://doi.org/10.1097/ALN.0000000000002506
5.Chang, Chun-Yu, et al. “Anesthesia and Long-Term Oncological Outcomes: A Systematic Review and Meta-Analysis.” Anesthesia & Analgesia, vol. 132, no. 3, Mar. 2021, pp. 623–34. https://doi.org/10.1213/ANE.0000000000005237
6.Huang, H., et al. “Prostate Cancer Cell Malignancy via Modulation of HIF-1α Pathway with Isoflurane and Propofol Alone and in Combination.” British Journal of Cancer, vol. 111, no. 7, Sept. 2014, pp. 1338–49. https://doi.org/10.1038/bjc.2014.426
7.HIF1A Hypoxia Inducible Factor 1 Subunit Alpha [Homo Sapiens (Human)] – Gene – NCBI. https://www.ncbi.nlm.nih.gov/gene/3091. Accessed 17 Aug. 2024.