Cancer Risk Following Bariatric Surgery

Aminian A, Wilson R, Al-Kurd A, Tu C, et al. Association of bariatric surgery with cancer risk and mortality in adults with obesity. JAMA 2022;327:2423–2433. Obesity has been shown to be related with various types of cancers, termed obesity-associated cancers, through multiple mechanisms involving circulating adipokines, inflammation, insulin, microbiota, and epigenetic changes. Whether weight loss can decrease the risk of obesity-associated cancers has been unclear, partly owing to difficulties in achieving sustained weight loss through diet and exercise, and the long follow-up period needed to assess cancer risk reduction. However, after bariatric surgery, patients typically lose 20%–35% of their body weight, which is often sustained for many years and provides a platform for assessing cancer risk over a longer time frame. In a retrospective matched cohort study, 5053 adult obese patients who underwent bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) were matched 1:5 with 25,265 patients who did not undergo surgery for their obesity, resulting in a total of 30,318 patients (median age, 46 years; median body mass index, 45; with 77% female and 73% White). At 10 years, patients in the bariatric surgery group had significantly greater weight loss, a lower incidence of obesity-related cancer (2.9% vs 4.9%; hazard ratio, 0.68), lower incidence of all types of cancer (6.8% vs 8.3%; hazard ratio, 0.83), and decreased cancer-related mortality (0.8% vs 1.4%; hazard ratio, 0.52). Regarding individual cancer types, the association was only significant for endometrial cancer. Despite the study demonstrating an important association, there are several notable limitations. First, the results cannot be generalized to men or different races/ethnicities. Second, the role of unmeasured potential selection bias remains an issue. For example, patients who undergo bariatric surgery could partake in a healthier lifestyles regarding dietary habits and physical activity, as well tobacco and alcohol use during follow-up than the nonsurgical control group, leading to healthy user bias. Third, screening practices could differ significantly between the 2 groups. In the present study, patients in the bariatric surgery group were more likely to have had screening tests for breast, colorectal, and prostate cancers compared with patients in the nonsurgical control group, which could lead to effective prevention and decreased cancer incidence. These points question whether a randomized controlled trial is needed to overcome potential selection bias, and if so, whether it is feasible to undertake given the challenges that would be needed to follow patients up for ≥10–20 years. Fourth, biological mechanisms related to specific cancer types should be further elucidated. The present study showed a significant association only for endometrial cancer, supported by previous data noting a decrease in endometrial proliferation and oncogenic signaling after bariatric surgery. In contrast, the available data are less clear and controversial regarding colon cancer incidence after bariatric surgery. Finally, it is unclear why there was a difference in both obesity-associated cancer and non–obesity-associated cancer (all types of cancer), therefore, suggesting a coexisting mechanism independent of weight loss.