On May 29th 2016 at the Euroanaesthesia Congress, a full lecture hall listened to the Pro-Con-Debate between our esteemed colleagues William Harrop-Griffiths and Donal Buggy regarding the potential of regional anaesthesia techniques to decrease the likelihood of metastases after cancer surgery. Dr. Buggy started out with an enthusiastic recapitulation of the current state of evidence regarding beneficial effects. His lecture reviewed basic and translational evidence, and findings from retrospective investigations. Dr. Harrop-Griffiths proceeded to caution that the potential of regional anaesthesia techniques was not as clear-cut as hoped in the absence of prospective trials. The discussion that followed touched on several subjects, including the question of whether regional anaesthesia techniques as such, or local anaesthetics absorbed into the systemic circulation, are responsible for the putative effect.
The perioperative period of cancer surgery is increasingly recognized as a crucial and defining moment. Surgical resection can lead to the dissemination of tumour cells, while some cancer cells may be left behind in the surgical field. At the same time, changes in the patients’ homoeostasis suppress the immune system, which is meant to take on these tumour cells. Some physiological mechanisms of the body are even exploited by tumour cells. For example, cancer cells can shroud themselves in micro-thrombi, thereby evading detection by the immune system. Thus, in theory, we should strive to preserve the immune system as much as possible, and this would mean attenuating the surgical stress response. As anaesthesiologists, we can all think of one prototypical intervention to achieve this, namely regional anaesthesia.
Over the past 10 years, substantial research efforts have been directed at the potential of perioperative drugs and interventions to optimize patient outcomes. This research has had two main directions. On one hand, very specific, direct, mechanisms such as inhibition of subcellular pathways (e.g., Src kinase, epigenetic reprogramming) was investigated. On the other hand, research focused on general, unspecific mechanisms like the above-mentioned reduction in surgical stress response or the reduction in drugs considered conducive to tumour progression, such as opiates. As of now, we do not know whether one or both research avenues will prove to be right. This was highlighted during the discussion, when Dr. Fassoulaki from Athens emphasized that while we as anaesthesiologists talk about “breast cancer”, gynaecologic oncologists have a list of several types of breast cancer, each with distinctive biological properties and characteristics.
Overall, we have accumulated a certain level of evidence for most perioperative interventions. Specifically, there is very recent clinical evidence that propofol might offer benefits compared to volatile anaesthetics, the use of non-steroidal anti-inflammatory drugs may be advantageous, and regional anaesthesia is at worst neutral or at best beneficial. The evidence supporting a negative role for opiates has become more nuanced and in some sophisticated models of tumour metastasis, even high doses of opiates do not promote cancer spread.
The consensus that was reached was that as of June 2016, in keeping with a literature reference by Dr. Marcel Durieux, no change in clinical practice can be recommended based solely on presumed anti-tumour effects. Rather, anaesthesia technique should be chosen based on best available evidence concerning patient status and type of surgery.
So what can we do in the operating room on a daily basis? For the example of major abdominal surgery for malignancy, we might usually go for a multimodal analgesic approach involving two non-opiates, thoracic epidural anaesthesia, and, if possible, propofol as the general anaesthetic to have the best shot at improving the patient’s condition in the perioperative period. This coincides with the limited evidence we have concerning tumour surgery. So by choosing the most protective and most effective combination of anaesthetics and analgesics, we are pretty close to the “dream regimen” from the point of view of cancer recurrence anyway. In the end, anaesthesia is called upon to provide a safe passage of the patient through his perioperative period, and by doing so, to the best of our knowledge, we might even contribute to the overarching goal of reducing the risk of recurring disease.
Lastly, there are reasons other than recurrence to use regional anaesthesia in tumour surgery. In thoracotomy and mastectomy, for example, regional techniques most likely decrease incidence of chronic pain, and for major visceral tumour surgery, regional anaesthesia decreases postoperative mortality, even though recurrence rate was unaffected.
By the end of this decade we will see the completion of trials into the effects of regional anaesthesia as well as intravenous local anaesthetics on tumour recurrence. These results will clarify whether we as anaesthesiologists can really influence tumour biology with our interventions. Until then, we should keep concentrating on providing the safest and gentlest possible transition of our patients through the perioperative period of cancer surgery.