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Anesthesia Technique Flops in Large Breast Cancer Trial

October 23, 2019 By No effect on recurrence or pain with regional method, opioid avoidance Christina Bennett

Despite expectations to the contrary, regional anesthesia-analgesia with paravertebral blocks and propofol during breast cancer surgery did not lower the risk of disease recurrence or incidence of persistent pain compared with general anesthesia with sevoflurane and opioids, a randomized trial found.

Among women in this large international study, the recurrence rate was the same (10%) for those who received regional anesthesia-analgesia and for those who received general anesthesia with opioids (HR 0.97, 95% CI 0.74-1.28, P=0.84), Daniel Sessler, MD, of the Cleveland Clinic in Ohio, and colleagues reported in The Lancet.

In addition, the proportion of patients who had persistent pain at 6 months after surgery was identical for the two anesthetic techniques (52%). At 12 months after surgery, the incidence of persistent pain remained similar for both, at 28% with the regional technique and 27% with general anesthesia (overall interim-adjusted odds ratio [OR] 1.00, 95% CI 0.85-1.17, P=0.99).

The frequency of neuropathic pain in the breast area was also the same for both techniques at 6 months after surgery (10%) and again at 12 months (7%).

“These robust findings disprove earlier expectations,” commented Faraj Abdallah, MD, of the University of Ottawa in Canada, and Duminda Wijeysundera, MD, PhD, of the University of Toronto in Canada, in a corresponding editorial.

Research suggests that volatile anaesthetics like sevoflurane can enhance cancer cells’ metastatic potential, the study authors explained, while opioids can inhibit immune function in humans and have been shown to promote breast tumor growth in mice.

On the other hand, mechanistic studies suggest that propofol has anti-inflammatory properties and keeps immune function intact, and although inconsistent, retrospective studies have reported fewer breast cancer recurrences among patients who received regional anesthesia. In addition, small studies have reported that using regional nerve blocks during breast cancer surgery may reduce the incidence and severity of persistent pain afterwards.

Sessler told MedPage Today that one way to look at the trial results is that the trial failed. “The other way to look at it is that anesthesiologists can use various different approaches per patient preference, and it won’t hurt anyone.”

He said that for most patients in the U.S. and internationally, paravertebral blocks are not used, so these findings will reinforce the current standard of using general anesthesia. “It means that people don’t have to change their anesthetic — what they’re doing already is the right thing.”

From 2007 to 2018, the trial enrolled more than 2,100 women younger than age 85 with primary breast cancer from 13 hospitals in eight countries. Most participants were from China (59.4%), followed by Ireland (19.2%), the U.S. (8.5%), and Austria (8.1%).

To be eligible, women could not have disease spread beyond the breast or axillary nodes and had to be scheduled for a mastectomy (unilateral or bilateral, with or without breast implants) or wide local excision with node dissection. Women were randomly assigned to one of the two anesthetic techniques.

A total of 1,043 women were randomized to receive regional anesthesia-analgesia and 1,065 to receive general anesthesia. The treatment groups were well balanced for patient demographics as well as several tumor and treatment characteristics, including tumor stage, receipt of neoadjuvant radiation or chemotherapy, surgery type, and year of surgery.

However, two patient characteristics (body-mass index and American Society of Anesthesiologists physical status) were not balanced between the treatment groups, but the difference was considered not clinically meaningful.

The trial also showed that quality of life and duration of hospitalization did not differ by anesthetic technique. In addition, neither serious adverse events related to regional anesthesia-analgesia nor cases of pneumothorax were seen. Nausea 1 day after surgery was more common after general anesthesia compared with regional anesthesia-analgesia (OR 0.47, 98.3% CI 0.37-0.60, P<0.0001), but this difference disappeared by day 2.

A subgroup analysis revealed differences between study sites, with Chinese sites trending toward a lower risk of breast cancer recurrence with regional anesthesia-analgesia (HR 0.77, 95% CI 0.55-1.09, P=0.15), but Sessler cautioned that the difference was neither “statistically significant” nor “clinically meaningful.”

One issue the editorial authors raised was that pain intensity and exposure to an inhaled volatile general anesthetic might have a dose-response relationship with risk of recurrence. They reasoned that because the duration of surgery was short — on average, 1.3 hours for both treatment groups — patients who received general anesthesia received relatively low amounts of opioids and had a relatively short exposure to the inhaled general anesthetic.

“Therefore, it is plausible that the benefits of regional nerve block and propofol anesthesia apply principally to patients undergoing prolonged procedures with more associated surgical pain,” they asserted.

Sessler expressed a similar view about the regional nerve block, saying: “This study doesn’t say that it’s not important for any type of surgery ever. It’s just for breast cancer.”

The study was funded by several entities, including internal sources, the Sisk Healthcare Foundation, Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Science Fund for Junior Faculty, Central Bank of Austria, and the National Healthcare Group. The funders did not participate in the study design, data collection, data analysis, data interpretation, or writing of the journal article.