William Harrop-Griffiths, Boyne Bellew
The ESA Focus Meeting on Regional Anaesthesia in the Perioperative Setting in Tel-Aviv in November 2017 dished up a particular delight: a clash of titans on the hottest topic in regional anaesthesia: Does the use of regional anaesthesia decrease the incidence of tumour recurrence after cancer surgery? Proposing the motion that regional anaesthesia prevents cancer recurrence was Dan Sessler from the Cleveland Clinic, USA, a leading academic who needs no introduction to any medical audience. Opposing him was William Harrop-Griffiths from London, UK, a man who always benefits from some sort of introduction. What follows is a summary of the points made during the debate, along with a recommendation of what anaesthetists should do if they wish to minimise the chances of cancer recurrence in their patients.
In 2006, Donal Buggy and Dan Sessler published a paper that suggested that regional analgesia during primary surgery for breast cancer might influence tumour recurrence.1 It was a retrospective study, as were several other studies published in the ensuing years that seemed to confirm a link between anaesthetic technique and cancer recurrence. The studies that suggested a link were balanced by some that suggested that there was no impact of anaesthetic technique and, given the drawbacks of retrospective studies and the variable findings, it became increasingly difficult to draw a firm conclusion on the issue. Members of the worldwide regional anaesthesia community, who for decades had been hoping that their clinical passion would at last be shown to affect one of the ‘big outcomes’ of medicine, could barely conceal their excitement, and many readily leapt aboard the ‘regional anaesthesia cures cancer’ bandwagon. Meanwhile, the people in white coats who work in laboratories and tend not to go to nightclubs at weekends got to work and proved plausible links between opiate drugs and cellular immunity in small animals and ex vitro human cells: opiates impair immunity and tumour recurrence is more likely when peri-operative immunity is impaired. A little over a year ago, the story seemed – at least to those of us who are passionate regional anaesthetists – clear: the use of regional anaesthetic and analgesic techniques minimises the use of opiates and thereby decreases tumour recurrence.
However, others were also using their retrospectoscopes: Tim Wigmore and his co-workers from the Royal Marsden Hospital in London, the UK’s premier cancer hospital, delved into their registries and found data that suggested that patients undergoing cancer surgery under total intravenous anaesthesia (TIVA) survived longer than a matched cohort who underwent surgery under inhalational anaesthesia. This brought great joy to the worldwide TIVA community who, just like the regional anaesthetists, had long been on the lookout for a good reason to justify the complexity of their clinical passion to other anaesthetists.
The current situation is as follows:
- There appears to be a ‘signal’ in retrospective studies suggesting that anaesthetic technique can have an influence on cancer recurrence.
- There seem to be two villains: opiates and volatile agents.
- Techniques that minimise the use of the villains are therefore potential heroes: regional anaesthesia and TIVA.
Many questions remain, not least of which is this: the TIVA technique used by the Royal Marsden Hospital uses large doses of Remifentanil, an opioid drug that, in theory at least, should be villainous to some extent. Would a combination of regional anaesthesia and opioid-free TIVA be the best of all techniques?
Buggy, Sessler, and co-workers wisely started a large-scale, multicentre, prospective, randomised study soon after their 2006 publication.3 In this study, tumour recurrence in two groups of patients is being studied: regional analgesia plus propofol anaesthesia, and opiates plus volatile anaesthesia. It is hoped that this study will indicate whether the ‘signal’ suggested by retrospective studies is supported by a properly conducted, prospective study. However, there are two potential problems with this study. The first is that even if there is a difference in recurrence between the two groups, it may not be possible to identify which of the two factors – avoidance of opiates and avoidance of volatiles – is the more relevant. Second, and perhaps more worryingly, this study was hoping to produce some results in 2018, but we are told that there will be some delay in this. The reason for this is that the power calculation of a study like this is dependent not on the number of patients who enter the trial but on the number who suffer recurrences. With overall improvements in cancer therapy, fewer and fewer patients are suffering recurrences, thereby delaying the results of the study. This opens up the prospect that by the time we can prove that anaesthetic technique affects tumour recurrence, cancer therapy will be so good that anaesthetic technique becomes irrelevant, returning the regional anaesthetists and TIVA enthusiasts to being two groups of odd people who play with ultrasound machines and algorithm-driven infusion pumps simply because they do.
What should we ordinary anaesthetists do while we wait for the Buggies, Sesslers, Wigmores, and white-coated people to give us definitive answers? My answer to this question is best summarised by Marcel Durieux4: ‘The good news is that if one adheres to best practices in anesthesiology, one, by and large, already uses a potentially optimal approach to the cancer patient. Decreasing postoperative opioid requirements by regional techniques, and by adopting a multimodal analgesic approach making maximum use of non-opioid adjuvants, including cyclooxygenase inhibitors, has many benefits apart from a putative role in preventing cancer recurrence. These approaches also limit volatile anesthetic requirements and reduce the surgical stress response, two factors implicated in recurrence. And our best practice already mitigates several other perioperative factors that have been suggested as relevant, including hypothermia, hypotension, anemia, and transfusion.’
Modesty prevents me from telling you who won the debate in the ESA meeting. All I will say is that the real winners were undoubtedly the registrants, who enjoyed a lively debate between two well-matched speakers on a fascinating topic.
- Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? 2006;105:660-4.
- Wigmore TJ, Mohammed K, Jhanji S. Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: a retrospective analysis. 2016;124:69-79.
- Sessler DI, Ben-Eliyahu S, Mascha EJ, Parat M-O, Buggy DJ. Can regional analgesia reduce the risk of recurrence after breast cancer? Methodology of a multicentre randomized trial. Contemp Clin Trials. 2008;29:517-26.
- Durieux ME. Anesthesia and cancer recurrence: improved understanding, but no reason for change. Anesth Analg. 2014;118:8-9.