In obese adults, bariatric surgeries nearly halve the risk of dying of cancer, compared with diet and other non-surgical ways of shedding unhealthy pounds, according to Cleveland Clinic research. The large, observational study, involving 30,318 patients, compared 5,053 obese patients who underwent bariatric surgery at the clinic to a matched control group of 25,265 obese patients who did not have surgery between 2004 and 2017.
The results found a 32 percent overall reduction in cancer risk and a 48 percent decreased chance of cancer-related death, according to Ali Aminian, MD, Director of the Cleveland Clinic's Bariatric & Metabolic Institute and the study's principal investigator. The reduction in risk for endometrial cancers-a cancer with the strongest association with obesity in women-proved especially high at 52 percent (JAMA 2022; doi:10.1001/jama.2022.9009).
To gain this benefit, however, "you need to lose 20-25 percent of your body weight and keep it off for a very long period of time," Aminian stressed, which many patients in the study were able to do over a 10-year period. On average, in fact, people who had weight-loss surgery lost 55 more pounds than those using medications and diet to control their obesity. Also, the greater the weight loss, the lower the risk of cancer.
Two in five Americans today are considered obese, with a dramatic rise in numbers in recent years, according to the Centers for Disease Control and Prevention. Not only does obesity increase the risk for at least 13 types of cancer-some more so than others-collectively, the agency estimates that they account for about 40 percent of all cancers diagnosed in the U.S. each year.
But, while obesity clearly contributes to cancer development, experts say, the exact mechanisms by which obesity raises the carcinogenic risk is not yet fully understood. A complex disease involving excessive amounts of body fat, obesity can accelerate tumor growth through chronic inflammation or produce high levels of insulin and insulin-like growth factors that stimulate sex hormones tied to several cancers. Fat cells also release hormones of their own that stimulate or inhibit cell growth-yet another potential pathway towards malignancy.
"Proving causation is far more difficult than proving association," said Edward Sauter, MD, PhD, a medical and program officer in the National Cancer Institute (NCI) Breast and Gynecologic Cancer Research Group. Even in cancers, where obesity has a strong link to cancer risk, he noted that multiple factors now widely under study are involved before cancer occurs.
Study Details
In the study SPLENDID (Surgical Procedures and Long-Term Effectiveness in Neoplastic Disease Incidence and Death), roughly two-thirds of patients in the surgical group underwent Roux-en-Y gastric bypass, while the remaining third underwent sleeve gastrectomy, a more contemporary procedure that blocks off most of the stomach.
All of the surgical patients fell within a broad range of body mass indexes between 35 and 80, with a mean BMI of 45. Although a BMI of 30 is considered the threshold for obesity, most insurance coverage for bariatric procedures typically begins at 35 BMI and patients need at least one obesity-related condition, such as heart disease or type 2 diabetes to qualify.
After 10 years, 96 patients in the bariatric surgery group and 780 patients in the non-surgical group developed an obesity-associated cancer. At the end of the follow-up period, 21 patients in the surgery group and 205 patients in the non-surgical group died from cancer. Differences between the two surgical groups were negligible, Aminian said. Both surgeries effectively reduced weight and cancer risk, with gastric bypass patients generally losing 15-20 pounds more on average than individuals who had sleeve gastrectomy.
SPLENDID's strength as a study lies in its large size and its 10-year follow-up period, according to NCI's Sauter. But, as with all studies where individuals are not randomized prospectively, there's the potential for bias, he cautioned. Individuals who undergo surgery, for example, may be healthier than their matched counterparts who do not have surgery.
Nevertheless, the study is an important one, he said, adding to the literature that shows that most high-risk patients with obesity benefit from surgery with sustainable weight loss. "Long-term weight loss averages 20-30 percent of total body weight, while at 1 year, it can be even a bit higher. This is far more than ordinarily achieved through lifestyle changes," he said.
While bariatric surgery was the focus of the SPLENDID study, Sauter noted that nonsurgical interventions are being investigated that could help individuals with less severe obesity to lose weight and mitigate obesity-associated health risks, including those for cancer.
One approved by the FDA last year is semaglutide, an injectable drug for chronic weight management that, together with caloric restriction and physical activity, helps regulate appetite and food intake in the brain by mimicking the hormone glucagon-like peptide 1. As the first weight-loss drug approved in nearly a decade, semaglutide brought significant weight loss in patients in several studies, up to 15-17 percent 1 year after starting medication. Several other drugs are in the pipeline that could prove even more effective, Sauter noted, eventually providing more options for patients.
Meanwhile, NCI recently announced two new research grants looking at whether the benefits of bariatric surgery arise from weight loss alone or whether there's a surgery-specific benefit, as these procedures top 250,000 or more in the U.S. annually. Investigators plan to look at increases in circulating bile acids triggered by these procedures, as well as changes in the gut microbiome when weight loss occurs, among other research avenues.
Susan Jenks is a contributing writer.