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  • Review Article
  • Published:

Perioperative events influence cancer recurrence risk after surgery

Nature Reviews Clinical Oncology volume 15, pages 205–218 (2018)Cite this article

Subjects

Key Points

  • Surgery remains the primary treatment for patients with solid tumours, yet postoperative locoregional recurrence and distant metastasis occur frequently and confer high risks of morbidity and mortality

  • Deleterious effects of surgery include the initiation of local and/or systemic inflammation, increased catecholamine levels, immunosuppression, a prothrombotic state, and exposure to anaesthetic agents; these processes overlap with cancer-promoting signalling pathways

  • Cancer cells that escape resection are subject to perioperative physiological changes and might disseminate and colonize distant organs, thus contributing to postoperative cancer recurrence

  • Perioperative use of β-adrenoceptor antagonists, anti-inflammatory drugs, intravenous anaesthetics, and antithrombotic agents is linked with improved survival outcomes in patients with cancer

  • >60% of patients with cancer are treated with surgery; therefore, offsetting the deleterious effects of surgery by use of affordable and readily available therapies might rapidly improve the postoperative survival of patients with cancer

Abstract

Surgery is a mainstay treatment for patients with solid tumours. However, despite surgical resection with a curative intent and numerous advances in the effectiveness of (neo)adjuvant therapies, metastatic disease remains common and carries a high risk of mortality. The biological perturbations that accompany the surgical stress response and the pharmacological effects of anaesthetic drugs, paradoxically, might also promote disease recurrence or the progression of metastatic disease. When cancer cells persist after surgery, either locally or at undiagnosed distant sites, neuroendocrine, immune, and metabolic pathways activated in response to surgery and/or anaesthesia might promote their survival and proliferation. A consequence of this effect is that minimal residual disease might then escape equilibrium and progress to metastatic disease. Herein, we discuss the most promising proposals for the refinement of perioperative care that might address these challenges. We outline the rationale and early evidence for the adaptation of anaesthetic techniques and the strategic use of anti-adrenergic, anti-inflammatory, and/or antithrombotic therapies. Many of these strategies are currently under evaluation in large-cohort trials and hold promise as affordable, readily available interventions that will improve the postoperative recurrence-free survival of patients with cancer.

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Figure 1: The effects of surgery and perioperative stress on cancer recurrence.
Figure 2: Putative mechanisms of postoperative cancer recurrence and metastasis.

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Acknowledgements

The work of the authors is supported by the Australian and New Zealand College of Anaesthetists, The David and Lorelle Skewes Foundation, the Peter Mac Foundation, and the National Cancer Institute (CA160890). N.J.P is the recipient of a Cancer Research UK Clinical Research Fellowship. Work in the G.P lab is supported by the British Journal of Anaesthesia/Royal College of Anaesthetists via the National Institute of Academic Anaesthesia, Cancer Research UK Grand Challenge award (C59824/A25044), and the Institute of Cancer Research.

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  1. Jonathan G. Hiller and Nicholas J. Perry: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgical Oncology, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Parkville, 3010, Victoria, Australia

    Jonathan G. Hiller, Bernhard Riedel & Erica K. Sloan

  2. Faculty of Medicine, Dentistry and Health Sciences, Building 181, University of Melbourne, Grattan Street, Parkville, 3010, Victoria, Australia

    Jonathan G. Hiller & Bernhard Riedel

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

    Jonathan G. Hiller, Bernhard Riedel & Erica K. Sloan

  4. Faculty of Medicine, Nursing and Health Sciences, Monash University, 35 Rainforest Walk, Clayton, 3800, Victoria, Australia

    Jonathan G. Hiller

  5. Division of Cancer Biology, Signalling & Cancer Metabolism Team, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    Nicholas J. Perry & George Poulogiannis

  6. Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, Exhibition Road, London, SW7 2AZ, UK

    George Poulogiannis

  7. Cousins Center for Neuroimmunology, Semel Institute for Neuroscience and Human Behavior, Jonsson Comprehensive Cancer Center, and University of California Los Angeles AIDS Institute, University of California Los Angeles, Medical Plaza 300, Suite 3160, Los Angeles, 90095, California, USA

    Erica K. Sloan

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J.G.H, N.J.P, B.R, and E.K.S researched data for the article. All authors wrote, reviewed, and edited the manuscript before submission. J.G.H and N.J.P contributed equally.

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Correspondence to Bernhard Riedel.

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Hiller, J., Perry, N., Poulogiannis, G. et al. Perioperative events influence cancer recurrence risk after surgery. Nat Rev Clin Oncol 15, 205–218 (2018). https://doi.org/10.1038/nrclinonc.2017.194

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