Obesity: bariatric surgery cuts the risk of developing cancer

A Cleveland Clinic study shows that among adults with obesity, weight loss achieved with bariatric surgery was associated with a 32% lower risk of developing cancer and a 48% lower risk of cancer-related death compared with adults who did not have the surgery. The research is published by JAMA.

Approximately 42% of American adults have obesity, according to the Centers for Disease Control and Prevention (CDC). Obesity increases the risk of developing 13 types of cancer that account for 40% of all cancers diagnosed every year in the United States, according to the CDC.

Ali Aminian, M.D., lead author of the study and director of Cleveland Clinic’s Bariatric & Metabolic Institute, said that bariatric surgery is currently the most effective treatment for obesity. “Patients can lose 20 to 40% of their body weight after surgery, and weight loss can be sustained over decades. The striking findings of this study indicate that the greater the weight loss, the lower the risk of cancer,” said Dr. Aminian.

The SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) research is a matched-cohort study that included more than 30,000 Cleveland Clinic patients. A group of 5,053 adult patients with obesity who had bariatric surgery between 2004 and 2017 were matched 1:5 to a control group of 25,265 patients who did not have surgery for their obesity.

After 10 years, 2.9% of patients in the bariatric surgery group and 4.9% of patients in the non-surgical group developed an obesity-associated cancer. The International Agency for Research on Cancer describes 13 types of cancer as obesity-associated cancers such as endometrial cancer, postmenopausal breast cancer, and cancers of the colon, liver, pancreas, ovary and thyroid.

After 10 years, 0.8% of patients in the surgery group and 1.4% of patients in the non-surgical group died from cancer. Those findings indicate that bariatric surgery is associated with a 48% lower risk of dying from cancer.

Researchers noted that the benefits of bariatric surgery were seen in a wide range of study participants, including both women and men, young and old, and Black and white patients. In addition, benefits were similarly observed after both gastric bypass and gastric sleeve operations.

“According to the American Cancer Society, obesity is second only to tobacco as a preventable cause of cancer in the United States,” said the study’s senior author, Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular and Thoracic Institute. “This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality.”

Numerous studies have shown the health benefits of bariatric or weight-loss surgery in patients with obesity. The Cleveland Clinic-led STAMPEDE study showed that following bariatric surgery, significant weight loss and control of type 2 diabetes last over time. The SPLENDOR study showed that in patients with fatty liver, bariatric surgery decreases the risk of the progression of liver disease and serious heart complications.

The SPLENDID study adds important findings to the literature focused on the link between obesity and cancer. Given the growing epidemic of obesity worldwide, these findings have considerable public health implications.

“Based on the magnitude of benefit shown in our study, weight loss surgery can be considered in addition to other interventions that can help prevent cancer and reduce mortality,” said Jame Abraham, M.D., chairman of the Hematology and Medical Oncology Department at Cleveland Clinic. “Further research needs to be done to understand the underlying mechanisms responsible for reduced cancer risk following bariatric surgery.”

Metabolic (bariatric) surgery (MBS) has been performed since 1954. To decrease food absorption, early procedures bypassed a portion of the small intestine by connecting the upper to the lower intestine with various modifications to decrease morbidity from the procedure due to malabsorption [1]. The two most commonly performed MBS procedures today are the Roux-en-Y gastric bypass (RYGB) and the sleeve gastrectomy (SG), comprising 78% of all MBS procedures performed in the U.S. in 2018 [2].

The adjustable gastric band was commonly performed in the past, but not currently (Figure 1). The RYGB is thought to be both restrictive and malabsorptive as it decreases the amount of food that can be consumed (restrictive) and bypasses most of the stomach and duodenum (malabsorptive), whereas the SG is restrictive but not as malabsorptive since the procedure restricts the amount of food that can be consumed (restrictive) but does not bypass the stomach or intestine (Figure 1).

Malabsorptive procedures generally alter bile acid concentrations in the intestine more than restrictive procedures. Most MBS procedures are now done laparoscopically. Laparoscopic MBS has a mortality rate of 0.1% and complication rate of 4%, which compares favorably with commonly performed surgical procedures such as gallbladder surgery, appendectomy, and knee replacement [3].

The average patient loses 70% of their excess body weight in the first 1–2 years after RYGB surgery [4]. The prospective Swedish Obese Subjects (SOS) study reported an average 32% total body weight loss 1–2 years after RYGB with sustained weight loss of 27% 15 years after surgery compared to 1% weight gain after the start of a lifestyle weight loss intervention [5].

In the same study, vertical banded gastroplasty (a restrictive procedure that was commonly performed in the past), demonstrated on average a total weight loss of 25% in the first 1–2 years with an average sustained loss of 18% at 15 years. Most MBS studies comparing RYGB to restrictive MBS procedures demonstrate greater weight loss after RYGB, with more side effects after RYGB due to the more complex nature of the surgical procedure and to postsurgical deficits in vitamin B12, iron, calcium, and folate.

There is evidence that MBS decreases type 2 diabetes mellitus (T2DM), cardiovascular (CV) risk, sleep apnea, and obesity driven cancers [5]. There is a significant improvement in glucose regulation among patients with T2DM who undergo MBS (improved insulin sensitivity, lower Hb1Ac) before significant weight loss [4].

The evidence of improvement in T2DM before much weight loss suggests that the health benefits of MBS are not simply due to the dramatic initial and sustained weight loss that occurs among most patients who undergo MBS. Using data from healthcare systems in the United Kingdom and Scandinavia, which provide some level of universal health care, MBS among eligible individuals was found to reduce healthcare costs, extend overall life on average by 0.8 years, and increase quality adjusted life by four years [6].

Nonetheless, MBS is only performed on one percent of the affected population [7]. There are clear changes in gut peptides and bile acids [4], adipose tissue function (with changes in adipokine production and decreased adipose tissue inflammation) [8], gut-brain signals (which lead to satiety despite decreased food consumption) [9], intestinal gluconeogenesis (an improvement in which has protective effects against diabetes and obesity by positively regulating glucose homeostasis and hepatic glucose production) [10], and an improved CV metabolic profile, including improvements in total cholesterol, triglycerides, and high and low density lipoproteins [11]. These observations provide convincing evidence that MBS consistently improves and often eliminates T2DM and lowers CV risk.

National Cancer Institute (NCI) Emphasis on Obesity
Obesity is one of four scientific priorities that are highlighted in the fiscal year (FY) 2022 NCI Annual Plan and Budget Proposal (https://www.cancer.gov/research/annual-plan/scientific-topics/obesity, accessed on 24 June 2021). As the plan outlines, almost 40% of adults are obese, including 35% of cancer survivors. Obesity increases the risk of death from cancer by 52% among men and 62% among women. The report mentions BS as an approach to control obesity that leads to a reduced risk of breast, colon, endometrial, and pancreatic cancers compared with obese controls.

The plan points out the importance of “uncovering the biology at the intersection of obesity and cancer,” and that it will be important to develop interventions based on the molecular mechanisms that drive obesity related cancer, such as changes in metabolism, hormone signaling, inflammation, and microbiome function. Additionally, the plan calls for studies evaluating the impact on cancer recurrence of weight loss among obese cancer survivors.

The plan mentions that in addition to the difficulty in losing weight, perhaps the biggest challenge with lifestyle weight loss strategies is weight loss maintenance. MBS has consistently been shown to be the most effective strategy to maintain weight loss once achieved.

For example, in the largest prospective study of MBS, the SOS, participants who underwent RYGB lost on average 32% of total body weight 1–2 years after surgery with a sustained weight loss of 27% 15 years after surgery compared to 1% weight gain 15 years after the start of a lifestyle weight loss intervention [5].

Indeed, ~90% of overweight and obese individuals who lose weight through lifestyle interventions regain all of the lost weight. The Look AHEAD trial, which compared an intense lifestyle intervention to usual medical care in highly motivated overweight or obese patients with T2DM found that participants regained about half of the weight lost, for an average weight loss of 4.7% at 8 years.

The study was terminated early since it failed to achieve its primary endpoint, a reduction in the incidence of adverse CV events. The study also did not identify a significant difference between the two groups in total cancer incidence, incidence of non-obesity related cancers, or total cancer mortality. There was a nonsignificant trend toward a reduction in obesity related cancers (hazard ratio 0.84, 95% CI: 0.68–1.04).

reference link https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268861/

More information: Ali Aminian et al, Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity, JAMA (2022). DOI: 10.1001/jama.2022.9009