Recurrence of Breast Cancer after regional or general anaesthesia: A randomised control trial.

Sessler D et al. Lancet 2019 November ; 394:1807-1815. :DOI: 10.1016/S0140-6736(19)32313-X

Clinical Question

  • In patients with breast cancer having potentially curative surgery, does a strategy of paravertebral block and propofol anaesthesia, compared to a strategy of opioid and sevoflurane anaesthesia, reduce local or metastatic recurrence?


  • Studies have debated the effect of anaesthetic technique on cancer recurrence
  • Volatile anaesthesia and opioids have been associated with immunosuppression and increased metastatic tumour cell activity in vitro, while propofol and regional anaesthesia have been shown to reduce those effects
  • Breast cancer is the most common cancer in women, causing 11,400 deaths a year
  • Previous studies have shown mixed results- some have suggested a reduction in breast cancer recurrences with regional anaesthesia, others have shown no difference


  • Randomised, multicentre, single blind study
  • 1:1 computerised generated randomisation, stratified by study site with random blocking
  • Allocation concealment until shortly before surgery
  • Follow up performed by blinded investigator
  • Intention-to-treat analysis
  • 356 recurrences need to be observed to give 85% power to detect 30% reduction in cancer recurrence
  • Interim analysis to be performed at 25%, 50%, and 75% of recruitment
  • Expected to complete in 5 years
  • Primary outcome method assessed using adjusted Cox proportion hazard model
  • Secondary outcomes assessed using Wilcoxon Rank Sum


  • 13 Hospitals across 8 countries
    • Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, USA
  • Jan 2007 to Jan 2018


  • Inclusion
    • Women <85
    • Primary breast cancer (tumour stage 1-3, nodes stage 0-2)
    • Unilateral or bilateral mastectomy, with or without implants OR
    • Wide local excision with node dissection
  • Exclusion:
    • Previous breast cancer surgery
    • Inflammatory breast cancer
    • Free flap reconstruction
    • ASA IV or higher
    • Contraindication to either approach
    • Another cancer
  • 2134 patients randomised, 2108 patients included in final analysis
  • Baseline demographics similar between groups
    • 59% recruitment from China


  • Ultrasound guided paravertebral block at T1-T5
    • Multiple injection technique used
  • Propofol 60–90mcg/kg/min as maintenance
  • Supraglottic airway preferred over ETT
  • Conventional general anaesthetic permitted if block failed


  • 1–3mcg/kg fentanyl, 2–4mg/kg propofol induction
  • ETT or Supraglottic airway
  • Sevoflurane in 20% Nitrous and 80% O2 maintenance
  • Ventilated to ETCO2 4kPa
  • Fentanyl boluses intraoperatively

Management common to both groups

  • Midazolam/fenanyl premed
  • Opioids as clinically necessary
  • Temperature control, haemoglobin targets, depth of anaesthesia monitoring, and management of PONV standardised
  • Paracetamol and NSAIDS as post-op analgesia
    • IV patient controlled analgesia (PCA) with opiates if needed
  • Transition to oral agents over 24 hours


  • Primary outcome: Recurrence free cancer survival
    • Study terminated at 50% analysis – 211 recurrences analysed
    • 102/1043 recurrences in regional group (10%) vs 111/1065 recurrences (10%) in GA group
    • No significant difference
    • No significant difference seen on multiple subgroup analyses
  • Secondary outcome:
    • Chronic pain at 6 and 12 months: no difference
    • Opioid consumption at 48 hours: no difference
    • PONV in recovery: 8% vs 20%
    • PONV at 48 hours: no difference

Authors’ Conclusions

  • Regional anaesthesia-analgesia by paravertebral blocks and propofol did not reduce breast cancer recurrence after potential curative surgery compared with general anaesthesia with the volatile anaesthetic sevoflurane and opioids for analgesia


  • Important clinical question
  • Randomised
  • Blinded
  • Registered on
  • Intention to treat analysis
  • Multi-centre recruitment providing strong external validity


  • Trial terminated early, so technically underpowered
  • Surgical technique not standardised
  • Slow recruitment (11 years)
    • Significant changes in breast cancer treatment during this time may have affected results
  • Paravertebral technique not standardised, limiting internal/external validity
  • Paravertebral technique used does not reflect what is currently considered best practice (a single targeted injection below the costotransverse ligament, with pleural drop as the end point)
  • The sensory level of the blocks were not tested prior to- or post- anaesthesia
    • While this may be important for blinding, it does bring into question their low block failure rate of 5/1043
  • The majority of the recruits were from China
    • While there were no differences seen on subgroup analysis by ethnicity, other factors such as surgical technique or medical follow up may have skewed results

The Bottom Line

  • This large RCT of opiate-free anaesthesia with paravertebral block compared to sevoflurane and opioid based anaesthesia did not show any differences in breast cancer recurrence rates
  • It was underpowered, slow to recruit, and did not standardise the regional technique used, and therefore is not a conclusive trial comparable to my local practice
  • The role of anaesthetic technique in cancer care remains uncertain

External Links


Summary author: Segun Olusanya
Summary date: 23 Nov 2019
Peer-review editor: Duncan Chambler

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