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Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis

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Abstract

Cancer, currently the leading cause of death in the population aged less than 85 years, poses a significant global disease burden and is anticipated to continue to increase in incidence in both developed and developing nations. A substantial proportion of cancers are amenable to surgery, with more than 60% of patients undergoing tumour resection. Up to 80% of patients will receive anaesthesia for diagnostic, therapeutic or palliative intervention. Alarmingly, retrospective studies have implicated surgical stress in disease progression that is predominantly characterised by metastatic disease—the primary cause of cancer-associated mortality. Our understanding of the mechanisms of surgical stress and impact of perioperative interventions is, however, far from complete. Accumulating evidence from preclinical studies suggests that adrenergic-inflammatory pathways may contribute to cancer progression. Importantly, these pathways are amenable to modulation by adapting surgical (e.g. minimally invasive surgery) and anaesthetic technique (e.g. general vs. neuraxial anaesthesia). Disturbingly, drugs used for general anaesthesia (e.g. inhalational vs. intravenous anaesthesia and potentially opioid analgesia) may also affect behaviour of tumour cells and immune cells, suggesting that choice of anaesthetic agent may also be linked to adverse long-term cancer outcomes. Critically, current clinical practice guidelines on the use of anaesthetic techniques, anaesthetic agents and perioperative adjuvants (e.g. anti-inflammatory drugs) during cancer surgery do not take into account their potential effect on cancer outcomes due to a lack of robust prospective data. To help address this gap, we provide an up-to-date review of current clinical evidence supporting or refuting the role of perioperative stress, anaesthetic techniques and anaesthetic agents in cancer progression and review pre-clinical studies that provide insights into biological mechanisms.

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Acknowledgements

This work was supported by the David and Lorelle Skewes Foundation, the Peter Mac Foundation, the Australian and New Zealand College of Anaesthetists and the National Cancer Institute (Grant No. CA160890).

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Cancer Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia

    Julia A. Dubowitz, Erica K. Sloan & Bernhard J. Riedel

  2. Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Julia A. Dubowitz, Erica K. Sloan & Bernhard J. Riedel

  3. UCLA Norman Cousins Center, Semel Institute for Neuroscience and Human Behavior, UCLA Jonsson Comprehensive Cancer Center, UCLA AIDS Institute, Medical Plaza 300, Los Angeles, CA, 90095, USA

    Erica K. Sloan

  4. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Grattan St, Melbourne, VIC, 3010, Australia

    Bernhard J. Riedel

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Dubowitz, J.A., Sloan, E.K. & Riedel, B.J. Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis. Clin Exp Metastasis 35, 347–358 (2018). https://doi.org/10.1007/s10585-017-9862-x

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