Perioperative Intravenous Lidocaine and Metastatic Cancer Recurrence - A Narrative Review

Abstract

Cancer is a major global health problem and the second leading cause of death worldwide. When detected early, surgery provides a potentially curative intervention for many solid organ tumours. Unfortunately, cancer frequently recurs postoperatively. Evidence from laboratory and retrospective clinical studies suggests that the choice of anaesthetic and analgesic agents used perioperatively may influence the activity of residual cancer cells and thus affect subsequent recurrence risk. The amide local anaesthetic lidocaine has a well-established role in perioperative therapeutics, whether used systemically as an analgesic agent or in the provision of regional anaesthesia. Under laboratory conditions, lidocaine has been shown to inhibit cancer cell behaviour and exerts beneficial effects on components of the inflammatory and immune responses which are known to affect cancer biology. These findings raise the possibility that lidocaine administered perioperatively as a safe and inexpensive intravenous infusion may provide significant benefits in terms of long term cancer outcomes. However, despite the volume of promising laboratory data, robust prospective clinical evidence supporting beneficial anti-cancer effects of perioperative lidocaine treatment is lacking, although trials are planned to address this. This review provides a state of the art summary of the current knowledge base and recent advances regarding perioperative lidocaine therapy, its biological effects and influence on postoperative cancer outcomes.

Keywords: anaesthesia; cancer; lidocaine; local anaesthetics; recurrence; surgery.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Wall and Buggy.

Figures

Figure 1

Schematic overview of pathophysiological mechanisms involved in peri-operative metastasis formation. ① As it develops, the primary tumour releases extracellular vesicles (EVs) containing growth factors, miRNAs etc. ② EV-contained factors create a pre-metastatic niche in distant organs by stimulating local cells such as fibroblasts, macrophages and mesenchymal stem cells to promote pro-neoplastic processes such as angiogenesis, inflammation and stromal remodelling. ③ During surgery, malignant cells are dispersed from the primary tumour and are released into the bloodstream to form circulating tumour cells (CTCs). ④ CTC are borne in the circulation to distant tissue beds where they arrest and extravasate into a pre-metastatic niche. ⑤ Survival conditions for the tumour cell are rendered even more favourable by the effects of mediators of the surgical stress response and inflammation, furthering the processes of angiogenesis, immune evasion etc. thus enabling the cancer cell to survive and proliferate and eventually form a clinically significant metastasis. (Created with BioRender®).

Figure 2

Potential anti-neoplastic mechanisms of action of systemic lidocaine during surgery. As a colonic tumour is excised (marked with *), tumour cells are released into the circulation to form circulating tumour cells (CTCs). These CTCs arrest within liver parenchyma where the likelihood of forming future clinically significant metastatic disease depends on the balance of pro- and anti-neoplastic processes present in the tumour microenvironment. Perioperative systemic lidocaine bathes the tumour cells and their microenvironment during this sensitive period and potentially beneficially alters the odds of host survival via an effect on any of ① - ④ outlined in the figure. (Created with BioRender®).