By: Jenna Bassett, PhD
“The leading cause of death after cancer surgery is the recurrence of cancer,” said senior study author Jin-Tae Kim, MD, PhD, of the Department of Anesthesiology and Pain Medicine at Seoul National University Hospital, South Korea. “If there is a difference in cancer recurrence rate according to the type of anesthesia used, even a small difference would make a big difference for patients.”
The retrospective study analyzed the effect of anesthesia administration on the long-term outcomes of 5,331 patients with breast cancer. The investigators used propensity score matching to ensure the IV and volatile anesthetic cohorts (1,766 in each group after matching) shared similar baseline characteristics.
Patients in the IV group were treated with propofol and remifentanil, and those in the volatile group received enflurane, isoflurane, sevoflurane or desflurane. The primary end point was recurrence-free survival following surgery, and the secondary end point was overall survival.
The Kaplan-Meier survival curves generated from these data showed no significant difference in 5-year, recurrence-free survival between the two cohorts (IV group, 93.2%; inhalation group, 93.8%; P=0.49). Additionally, there was no significant difference in the 5-year overall survival rate between the IV and inhalation groups (94.2% and 94.5%, respectively; P=0.37).
Dr. Kim and his colleagues developed a Cox proportional hazards model for recurrence-free survival to further investigate whether the type of anesthesia had an effect on long-term outcomes after breast cancer surgery. Based on this model, the odds for recurrence-free survival were similar in each anesthetic approach (hazard ratio, 0.96; 95% CI, 0.69-1.32; P=0.78).
The results of these analyses indicate there is no association between the type of anesthesia used for surgery and the patient’s long-term outcomes. Factors that were associated with a higher risk for disease recurrence and all-cause mortality included age younger than 40 years, nonadherence to standard cancer therapy, and breast cancer subtypes other than luminal-A.
Based on the study results, Dr. Kim said, “Both anesthetic techniques can be used for breast cancer surgery, and the choice of anesthetic agent should be made according to the characteristics of the individual patient. Selection of IV or volatile anesthesia should be based on factors other than cancer recurrence.”
Anesthesia and Cancer Prevention
Although surgical resection can be a curative procedure, the surgery itself has a potential to support metastasis or progression of minimal residual disease. For example, natural killer cells, the body’s major anticancer defense system, can be impaired by inflammation and immunosuppression—occurrences commonly associated with major surgery. Identifying the surgical elements that can affect these factors and finding ways to mitigate or prevent damage should reduce the risk for developing recurrent or metastatic disease after surgery.
Anesthesia has the potential to both promote and prevent disease recurrence. Propofol, for example, has antioxidant and anti-inflammatory effects that may prevent recurrence, while volatile anesthetics can harm immune system function, potentially increasing cancer recurrence risk.
“If anesthetic management has even a small influence on cancer recurrence, we need to take the possibility seriously,” said Daniel I. Sessler, MD, of the Department of Outcomes Research at the Anesthesiology Institute, Cleveland Clinic, in Ohio. “There are mechanistic reasons to believe that both regional analgesia and intravenous anesthesia might be protective, and animal research is also supportive. On the other hand, there is currently limited and contradictory clinical evidence—mostly retrospective.”
Several groups have investigated the possible link between the use of anesthesia and cancer recurrence, but these studies have had variable results. Whereas some studies show reduced inflammation, decreased risk for recurrence, or improved prognosis associated with anesthesia use across a variety of cancers, other studies, including this most recent work, show no relationship between anesthesia and long-term outcomes.
An editorial by Dr. Sessler in the same issue of Anesthesiology (2019;130:3-5) as Dr. Kim’s study suggested that the invasiveness of the surgery itself may play a role. “To the extent that anesthetic management might influence cancer recurrence, it most likely does so in the context of large invasive operations that produce considerable inflammatory response and postoperative pain.”
However, existing studies are limited and many studies are retrospective, meaning experimental control and data are constrained. In addition, surgical procedures vary, and the molecular landscapes and tumor microenvironments differ across cancer subtypes and individual patients.
“The relationship between anesthetic management and cancer recurrence is exciting,” Dr. Sessler said. “But the research remains at an early stage. Current results are sparse and contradictory in humans.” Future research may translate into practice changes that decrease cancer risk, but for now, more studies are needed to understand the impact of anesthesia in different contexts.
Dr. Kim and his colleagues noted the need for additional large randomized clinical trials to gain better insight into the link between anesthesia and disease recurrence. “In fact, large randomized trials comparing cancer recurrence and survival with volatile and intravenous anesthesia for major cancer surgery are already in progress. We anticipate these results.”
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.