By Michael Vlessides

Regional anesthesia and analgesia with paravertebral blocks and propofol do not reduce the recurrence of breast cancer after surgery when compared with volatile general anesthesia with sevoflurane and opioids, a study has concluded.

The international multicenter trial also found that the frequency and severity of persistent postoperative pain were similarly unaffected by anesthetic technique.

“Surgery is the primary treatment for most cancers, and recurrent cancers are often lethal,” said Daniel I. Sessler, MD, the Michael Cudahy Professor and Chair of the Department of Outcomes Research at Cleveland Clinic in Cleveland. “If there is anything that we can do to reduce cancer recurrence, even just a little, we will save many lives.

“It may seem unlikely that anything that anesthesiologists do for a couple of hours would have any effect on cancer recurrence, which occurs months to years later,” he added. “But there are reasons to believe that we might.”

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Indeed, regional anesthesia and analgesia have been shown to ameliorate three perioperative factors that impair host defense against cancer:

  1. the surgical stress response;
  2. use of volatile anesthetics; and
  3. consumption of opioids for analgesia.

“These factors led us to our primary hypothesis: that recurrence of breast cancer is less common with paravertebral anesthesia and analgesia than with volatile general anesthesia and opioids,” Dr. Sessler said.

“Our secondary hypothesis was that regional analgesia reduces persistent pain. The basis for this hypothesis is the strong association between acute postoperative pain and persistent pain. Nobody knows if the relationship is causal, but this association shows up in study after study. Since paravertebral analgesia is effective, it might well reduce persistent incisional pain.”

To test these hypotheses, Dr. Sessler and his colleagues enrolled 2,132 women into the multicenter, randomized controlled trial between Jan. 30, 2007, and Jan. 18, 2018. The trial was performed at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore and the United States.

Participants all had breast resections for potentially curative cancers. They were randomized to either regional anesthesia and analgesia with paravertebral block and propofol sedation or to sevoflurane general anesthesia with opioid analgesia.

“The women had at least a partial mastectomy and node dissections,” Dr. Sessler explained. “They were not just simple lumpectomies.”

Similar Post-op Radiation And Chemotherapy

The trial’s primary outcome was cancer recurrence, either local recurrence or metastatic breast cancer. Secondary outcomes included incisional pain at six and 12 months.

“This was a cumulative incidence study, which meant the sample size was based on the number of recurrences, not the number of patients enrolled,” Dr. Sessler explained. The trial was planned for a total of 351 recurrences.

There were 1,043 women assigned to the regional anesthesia group and 1,065 allocated to general anesthesia. Baseline characteristics were well balanced between the groups, and median follow-up was 36 months.

“About half the patients got postoperative radiation, and about half got postoperative chemotherapy,” Dr. Sessler noted.

The investigation found 102 recurrences (10%) among women assigned to regional anesthesia and analgesia, compared with 111 (10%) in their counterparts randomized to general anesthesia (hazard ratio, 0.97; 95% CI, 0.74-1.28; P=0.84).

Given these results, the study was stopped because of futility, according to a set of a priori rules. “There was absolutely no difference between the groups,” Dr. Sessler said.

These findings illustrate that regional anesthesia and analgesia with a paravertebral block and propofol do not reduce the incidence of postoperative breast cancer recurrence compared with volatile general anesthesia and opioids.

“Let me note, though, that these were relatively small operations,” he added. “And that’s important because small operations don’t cause as much surgical stress response as something like a major open abdominal surgery. So there’s less inhibition of natural killer cells from a small operation than from a big one.

“Regional anesthesia–analgesia might possibly still be helpful, but it needs to be tested in much larger operations,” he added. “But at least for breast cancer, it clearly doesn’t work.”

Persistence of Pain Also Similar

The trial also found no difference in persistent pain between the groups at either six or 12 months. Indeed, incisional pain was reported by 52% of regional anesthesia–analgesia patients and 52% of general anesthesia patients at six months. By 12 months, 28% of regional anesthesia–analgesia patients and 27% of general anesthesia patients reported such pain (overall interim-adjusted odds ratio, 1.00; 95% CI, 0.85-1.17; P=0.99).

Similarly, neuropathic breast pain did not differ in patients by anesthetic technique, occurring in 10% of patients in each of the treatment groups at six months, and 7% in each group at one year.

“So despite the strong association between acute postoperative pain and persistent pain, this did not appear to be a causal relationship because blocking the acute pain did not reduce persistent pain,” Dr. Sessler said.

Given recent emerging evidence, Juan P. Cata, MD, an assistant professor of anesthesiology and perioperative medicine at the University of Texas MD Anderson Cancer Center, in Houston, said he was not particularly surprised by the findings of the current investigation. “There are still a lot of people who hypothesize that anesthetics might influence tumor progression,” Dr. Cata said. “And while in vitro and animal studies have shown some interaction between anesthetics and tumor progression, the human studies are not showing the same in terms of regional anesthesia.”

That said, Dr. Cata also recognized the need for continuing research in the area. “I think the question remains open for different anesthetics, techniques and patient populations within,” he explained. “But these kinds of studies are not easy to do. They are very large and very expensive. So it’s going to take at least a few years to know whether we have an anesthetic technique that might influence overall survival in patients.”

Dr. Sessler reported these findings at a special session of the 2019 annual meeting of the American Society of Anesthesiologists, with simultaneous publication in the Lancet (2019;394[10211]:1807-1815).


Drs. Sessler and Cata reported no relevant financial disclosures. The trial was funded by Sisk 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.