Clinical Context

Bariatric surgery is usually associated with weight loss equivalent to 20% to 35% of body weight among obese patients. Moreover, there is growing evidence that the weight loss associated with bariatric surgery yields meaningful improvements in the risk for severe disease associated with obesity. The authors of the current study previously evaluated the risk for cardiovascular disease after bariatric surgery in a large patient cohort. Their results were published in the October 1, 2019, issue of JAMA.^[1]

The study compared cardiovascular outcomes among 13,722 adults with diabetes and obesity. Patients who completed bariatric surgery were compared with those who did not in a 1:5 ratio. At the end of the study follow-up period of 8 years, rates of incident cardiovascular events were 30.8% in the surgical group and 47.7% in the nonsurgical group (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.55-0.69). Bariatric surgery was superior to no surgery in all 7 individual components of the composite primary outcome, and surgery was also associated with an HR for overall mortality of 0.59 (95% CI, 0.48-0.72).

The authors of that study now examine the potential efficacy of bariatric surgery against the risk for cancer related to obesity.

Study Synopsis and Perspective

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer compared with peers who did not have the surgery.

"The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk," lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, told Medscape Medical News.

The study was published online June 3 in JAMA and presented at the American Diabetes Association 82nd Scientific Sessions, underway in New Orleans, Louisiana.^[2]

Best Evidence to Date

"We know that obesity is strongly linked with different types of cancers, but we didn't know if losing a significant amount of weight can significantly decrease the risk of cancer," Dr Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with just 2.7 kg (6 pounds) for their peers who did not have the surgery, for a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate, 3.0 vs 4.6 events, respectively, per 1000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs 4.9% in the nonsurgery group; absolute risk difference, 2.0%; 95% CI, 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P=.002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the effect of bariatric surgery on individual cancer types was not possible.

In the fully adjusted Cox models, the association between bariatric surgery and individual cancer types was only significant for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a "trend or signal toward a reduction in their risk after the surgery," Dr Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

"So, it was not surprising that we had more cases of endometrial cancer than other types of cancer," he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years with vs without bariatric surgery (0.8% vs 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P=.01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer-protective effect, patients need to lose at least 20% to 25% of their body weight, which is almost impossible with diet alone, Dr Aminian said.

Obesity is "second only to tobacco" as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic in Ohio, said in a news release.

"This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality," Dr Nissen said.

Questions Remain

In an accompanying editorial, Anita P. Courcoulas, MD, MPH, from the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, says future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.^[3]

"It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors," Dr Courcoulas points out.

"In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans," she says.

"If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial," Dr Courcoulas concludes.

The study had no specific funding. Dr Aminian reported receiving grants and speaking honoraria from Medtronic. Dr Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article. Dr Courcoulas has disclosed no relevant financial relationships.

JAMA. Published online June 3, 2022.

American Diabetes Association (ADA) 82nd Scientific Sessions. Presented June 3, 2022.

Clinical Implications

• A previous study found that bariatric surgery was effective in the prevention of cardiovascular disease among patients with obesity and diabetes, with an HR of 0.61 for this outcome compared with no surgery. Bariatric surgery was also associated with a lower risk for all-cause mortality.
• The current study demonstrates that bariatric surgery can be effective in reducing the risks for obesity-related cancer, all incident cancer, and cancer-related mortality.
• Implications for the healthcare team: The healthcare team should advise patients considering bariatric surgery not only of the weight loss benefits associated with these procedures but also of an improvement in long-term health outcomes.

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