What makes this a landmark study?

Since Exadaktylos’ (2006) extraordinary retrospective study showing a 30% reduction in breast cancer recurrence with a regional analgesia technique, we have been anxious to learn whether anaesthetic choice my impact cancer outcome.

Various in vitro studies suggested plausible explanations for how opioids and volatiles could promote cancer recurrence, although quality evidence remainded missing.

The Breast Cancer Recurrence Collaboration has filled this gap, setting out to answer this question with an international, multicenter, randomised controlled trial.

What did they do?

Over 12 years 2,132 women were enrolled and ranomised to either paravertebral block & propofol, or sevoflurane. Some in the paravertebral group were exposed to sevoflurane when required (17%), and did receive intraoperative fentanyl, although roughly half as much on average as the volatile group.

And they found?

There was no difference in cancer recurrence rate or persistent wound pain between groups. Even when analysing only patients who received no sevoflurane (83% of regional group) no difference was identified.

This does not mean that a paravertebral technique offers no benefit: it almost eliminated the need for volatile anaesthesia, reduced opioid demand and reduced post-operative nausea & vomiting – all positive outcomes. But it did not reduce cancer recurrence.

Be smart

This result cannot be generalised beyond breast cancer to more invasive, stress-inducing cancer surgery (eg. prostatectomy, pneumonectomy). Our knowledge of perioperative factors that depress host defences (surgical stress, volatiles and opioids) are still relevant when we consider how anaesthetic choices may contribute to improving patient outcomes.

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• Daniel I Sessler, Lijian Pei, Yuguang Huang, Edith Fleischmann, Peter Marhofer, Andrea Kurz, Douglas B Mayers, Tanja A Meyer-Treschan, Martin Grady, Ern Yu Tan, Sabry Ayad, Edward J Mascha, Donal J Buggy, and Breast Cancer Recurrence Collaboration.
• Department of Outcomes Research, Anesthesiology Institute and Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: ds@or.org.
• Lancet. 2019 Nov 16; 394 (10211): 1807-1815.

BackgroundThree perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain.MethodsWe did a randomised controlled trial at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, and the USA. Women (age <85 years) having potentially curative primary breast cancer resections were randomised by computer to either regional anaesthesia-analgesia (paravertebral blocks and propofol) or general anaesthesia (sevoflurane) and opioid analgesia. The primary outcome was local or metastatic breast cancer recurrence. The secondary outcome was incisional pain at 6 months and 12 months. Primary analyses were done under intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT00418457. The study was stopped after a preplanned futility boundary was crossed.FindingsBetween Jan 30, 2007, and Jan 18, 2018, 2132 women were enrolled to the study, of whom 24 were excluded before surgery. 1043 were assigned to regional anaesthesia-analgesia and 1065 were allocated to general anaesthesia. Baseline characteristics were well balanced between study groups. Median follow-up was 36 (IQR 24-49) months. Among women assigned regional anaesthesia-analgesia, 102 (10%) recurrences were reported, compared with 111 (10%) recurrences among those allocated general anaesthesia (hazard ratio 0·97, 95% CI 0·74-1·28; p=0·84). Incisional pain was reported by 442 (52%) of 856 patients assigned to regional anaesthesia-analgesia and 456 (52%) of 872 patients allocated to general anaesthesia at 6 months, and by 239 (28%) of 854 patients and 232 (27%) of 852 patients, respectively, at 12 months (overall interim-adjusted odds ratio 1·00, 95% CI 0·85-1·17; p=0·99). Neuropathic breast pain did not differ by anaesthetic technique and was reported by 87 (10%) of 859 patients assigned to regional anaesthesia-analgesia and 89 (10%) of 870 patients allocated to general anaesthesia at 6 months, and by 57 (7%) of 857 patients and 57 (7%) of 854 patients, respectively, at 12 months.InterpretationIn our study population, regional anaesthesia-analgesia (paravertebral block and propofol) did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anaesthesia (sevoflurane) and opioids. The frequency and severity of persistent incisional breast pain was unaffected by anaesthetic technique. Clinicians can use regional or general anaesthesia with respect to breast cancer recurrence and persistent incisional pain.FundingSisk Healthcare Foundation (Ireland), Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Peking Union Medical College Hospital, Science Fund for Junior Faculty 2016, Central Bank of Austria, and National Healthcare Group.Copyright © 2019 Elsevier Ltd. All rights reserved.

This article appears in the collections: Anesthesia technique and cancer recurrence and Landmark articles in Anesthesia.

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