Colorectal Cancer Surgery Outcomes Unaffected By General Anesthetic

By MICHAEL VLESSIDES

The choice of general anesthetic regimen—either total intravenous anesthesia (TIVA) or volatile anesthesia—does not appear to affect cancer outcomes after colorectal surgery.

The authors of this systematic review and meta-analysis noted that these findings contrast with previous studies, which showed a protective effect of TIVA in other types of cancer surgery.

“There is both clinical and preclinical evidence which suggests that even though exposure to anesthesia is brief, it can potentially have significant clinical impact on outcome after cancer surgery,” said Zhaosheng Jin, MD, a resident at Stony Brook Medicine, in New York. “This project looks at the clinical evidence for whether there’s any significant outcome change between different choices of anesthesia for colorectal cancer surgery, which is one of the most common cancer types in the U.S.”

As part of the investigation, Dr. Jin and his colleagues conducted a literature search of the PubMed, Central, EMBASE, CINAHL, Google Scholar and Web of Science databases for clinical studies that compared adult patients who underwent potentially curative colorectal cancer surgery under general anesthesia with total intravenous propofol or with volatile anesthetic agents. The researchers extracted a variety of data from each investigation, including cancer recurrence, recurrence-free survival rate and mortality.

“One thing we wanted to exclude to minimize confounding was the concurrent use of regional anesthesia,” Dr. Jin said. “That is another intervention that is thought to affect the outcome of cancer surgeries.”

A Surprising Lack of Difference

In a presentation at the 2021 virtual annual meeting of the International Anesthesia Research Society (abstract 849), Dr. Jin said that the literature search was conducted through early January 2021. By that point, the investigators had identified a total of four fairly large studies comparing TIVA and volatile anesthesia in colon cancer surgery, each of which was assessed for quality using the Quality of Prognostic Studies (QUIPs) tool: • Enlund et al. Ups J Med Sci. 2014;119(3):251-261; • Hasselager et al. Br J Anaesth. 2020;126(5):921-930; • Makito et al. Anesthesiology. 2020;133(4):764-773; and • Wu et al. Anesthesiology. 2018;129(5):932-941.

All of the investigations reported mortality rates after follow-up periods ranging from two to five years. The meta-analysis did not find any significant difference between TIVA and volatile anesthesia for all-cause mortality (hazard ratio [HR], 0.76 for TIVA; 95% CI, 0.54-1.08).

The rate of cancer recurrence was reported by two studies. The researchers found no significant difference between TIVA and volatile anesthesia, yielding an HR of 0.80 for TIVA (95% CI, 0.58-1.09). Finally, two studies examined recurrence-free survival, which again showed no significant difference between the two anesthetic approaches (HR, 1.02 for volatile anesthesia; 95% CI, 0.91-1.15).

As Dr. Jin discussed, the findings proved surprising to the researchers, given preclinical data suggesting that propofol and volatile anesthesia have different effects on cancer cells.

“On the other hand, cancer is a very broad and arguably nebulous term,” he noted. “Different kinds of cancer cell lines have very different phenotypes, and different types of surgeries will have different physiological impacts on the possible recovery period. So, it may just be that colorectal cancer is not something that is affected by the use of TIVA versus volatile anesthesia.”

These findings, Dr. Jin added, contrast with previous research conducted by him and his colleagues. “We did a similar study looking at breast cancer a couple of years ago and found that the choice between volatile anesthesia and TIVA does have some impact in terms of outcomes.”

While the current study did not yield similar results, the researchers believe the relatively small pool of studies may play a part, and more studies are needed for reliable evidence.

A Robust Randomized Trial Needed

“The limitations of retrospective analyses are well known, with nonrandom treatment allocation and unobserved confounding being the most important,” commented Daniel I. Sessler, MD, the Michael Cudahy Professor and chair of the Department of Outcomes Research at Cleveland Clinic.

“Combining four registry studies in a meta-analysis does not lessen the major limitations of retrospective analyses, which rarely include sample size. What we need now is a robust randomized trial. Fortunately, VAPOR-C recently started and should provide clear evidence supporting or denying the theory that intravenous anesthesia improves cancer-free survival.”

VAPOR-C is the Volatile Anaesthesia and Perioperative Outcomes Related to Cancer trial (ClinicalTrials.gov Identifier: NCT04316013), based in Australia and New Zealand, and has a target sample size of 5,736. ■

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