No link between duration or depth of general anesthesia and subsequent cancer risk

Helping to allay fears raised by previous studies, a new report finds no link between the duration or depth of general anesthesia and the subsequent risk of developing cancer, according to the October issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

"Neither duration of anesthesia nor increased cumulative time with profound sevoflurane anesthesia was associated with an increased risk for new malignant disease within five years after surgery in previously cancer-free patients," concludes the study by Maj-Lis Lindholm, Ph.D., and colleagues of the Karolinska Institute, Stockholm. An accompanying editorial highlights the importance of publishing and disseminating the results of such "negative" follow-up studies.

No Link between Anesthesia and Subsequent Cancer Risk

The researchers analyzed data on nearly 3,000 Swedish patients undergoing surgery with the inhaled general anesthetic sevoflurane. None of the patients had any known cancer at the time of the surgery.

The duration and depth of anesthesia were analyzed as predictors of the later risk of cancer. (Depth of anesthesia was assessed using technique called bispectral index [BIS] monitoring.) Sevoflurane—one of the most widely used inhaled anesthetics—was chosen for study based on data suggesting that it may reduce immune responses during surgery.

Five years after surgery, 4.3 percent of the patients had developed cancer. On analysis adjusting for other factors, there was no association between the duration of anesthesia and the risk of developing cancer during follow-up. Cancer risk was also unrelated to time spent at various depths of anesthesia, based on different BIS cutoff points.

Despite the lack of association with anesthesia, the rate of cancer in this group of surgical patients was higher than expected. The reasons for this increase—37 percent higher than in the general population—could not be determined. However, there was no evidence that it reflected factors related to patient selection bias or other medically significant reasons.

Negative Results Provide Important Follow-up on Previous Research

Recent studies have raised the possibility that anesthesia or other factors around the time of cancer surgery may increase the risk of cancer recurrence. One theory is that anesthesia affects the immune system, allowing otherwise dormant cancer cells to progress into clinical disease. The new study is the one of the first to look at whether general anesthesia for surgery affects the risk of developing cancer in initially cancer-free patients.

The results provide no evidence that the duration or depth of sevoflurane anesthesia affects the risk of new-onset cancer. Dr. Lindholm and coauthors emphasize that their findings do not apply to patients undergoing cancer surgery, or those with previous cancer. They also note that their study cannot explain the possible increase in cancer risk among patients undergoing surgery, compared to the general population.

In an editorial, Dr. Kate Leslie of University of Melbourne, Australia, and Dr. Timothy G. Short of Auckland City Hospital, discuss the importance of "negative" studies refuting previous results. There's a recognized phenomenon of "publication bias" and other forms of "dissemination bias," in which follow-up studies don't get the same attention as initial, high-profile findings—and sometimes aren't published at all.

Drs. Leslie and Short hope the new report will influence further research to build on the results. They suggest that it might be better to perform further observational studies before any large randomized trial on the effects of general anesthesia on cancer risk. They conclude, "[I]f there is a small effect that has been missed by this study, a very large and expensive trial would be required to detect it."

Like other major medical journals, Anesthesia & Analgesia has made a concerted effort to reduce discrimination against negative studies. "The new results are good news—there was no increase in the rate of new cancer in previously cancer-free patients undergoing general anesthesia," comments Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia & Analgesia. "Although this was a 'negative' study, it had adequate statistical power to identify small changes in cancer risk associated with anesthesia."