SPLENDID unmasks benefits of bariatric surgery in cancer

New evidence from the SPLENDID study unmasks the benefits of weight loss achieved with bariatric surgery in protecting against cancer.

“What we know is obesity is strongly linked with different cancer types,” said lead investigator Dr Ali Aminian, director of the Bariatric & Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, US, at ADA 2022. “What we didn’t know is losing a significant amount of weight can significantly decrease a person's cancer risk.”

In the study, obese adults who underwent bariatric surgery had a 32-percent lower risk of developing cancer and a 48-percent lower risk of dying from the disease vs their counterparts who did not go for surgery.

“The magnitude of benefit was large and dose-dependent, with more weight loss associated with a greater reduction in cancer risk,” reported Aminian.

The study was subsequently published online. [JAMA 2022;doi:10.1001/jama.2022.9009]

The SPLENDID study included over 30,300 obese adults (median age 46 years, over 75 percent women, median BMI was 45 kg/m²). Over 5,000 patients who underwent the Roux-en-Y gastric bypass (66 percent) or sleeve gastrectomy (34 percent) were matched in a 1:5 ratio to 25,265 patients who did not go for bariatric surgery.

Significant weight loss with bariatric surgery

At 10 years, patients who underwent bariatric surgery had lost 27.5 kg vs 2.7 kg in those who did not go for surgery, for a difference of 19.2 percent. 

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 obesity-associated cancer (incidence rate was 3.0 vs 4.6 events per 1000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower with bariatric surgery (2.9 percent vs 4.9 percent with control, absolute risk difference 2.0 percent; adjusted hazard ratio [adjHR], 0.68; p=0.002). Most cancer types were also less common with bariatric surgery.

Endometrial cancer had the strongest association with obesity, which did not surprise Aminian.  “Patients who seek bariatric surgery are typically obese, middle-aged women. Hence, it didn’t come as a surprise that we had more cases of endometrial cancer vs other cancer types.”

For other cancer types, there was a trend or signal toward risk reduction after bariatric surgery.

In terms of cancer-related mortality,  there was a reduction seen with bariatric surgery (0.8 percent vs 1.4 percent; p=0.01) at 10 years. The benefits were observed with both gastric bypass and sleeve gastrectomy in both Black and White patients, younger and older alike, regardless of gender.

“Patients need to lose 20–25 percent of their body weight to achieve the cancer-protective effect,”  which he said is unachievable with diet and exercise alone.

More work forthcoming

In an accompanying editorial, Dr Anita Courcoulas from the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania, US explained that obesity promotes and accelerates cancer growth by multiple mechanisms, including increases in circulating adipokines, insulin, and insulin growth factor, circulating oestrogens, inflammatory cytokines, changes in microbiota, and epigenetic changes. “However, definitive data on the effect of intentional weight loss through interventional studies and cancer risk reduction are lacking.” [JAMA 2022;doi:10.1001/jama.2022.9166]

Although the study lends support to findings that patients who had bariatric surgery may experience a decreased risk for cancer, she said more work needs to be done through large, well-designed studies. “If the association is further validated, the benefits of bariatric surgery would extend to long-term health and prevention. This could then further guide for whom bariatric surgery is most beneficial,” she added.