https://jamanetwork.com/journals/jama/fullarticle/2793220
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Here is the Discussion and Conclusion:
Discussion
In this matched cohort study with long-term follow-up, bariatric surgery was associated with a significant reduction in the risk of obesity-associated cancer, all invasive cancer types, and cancer-related mortality.
Examining a cancer prevention intervention in a randomized clinical trial is challenging.2,3 In the absence of randomized clinical trials, carefully conducted observational studies can provide potentially useful data on the role of intentional weight loss on cancer risk. In the long-term follow-up of the well-matched Swedish Obese Subjects (SOS) study9 that included 2010 surgical and 2037 matched control patients, bariatric surgery was significantly associated with lower risk of cancer (HR, 0.67 [95% CI, 0.53-0.85]). In the SOS study,9 87% of the bariatric surgical procedures were either gastroplasty or gastric banding, which have been replaced by more effective procedures in recent years. A large multicenter study from the Kaiser Permanente health system reported a lower risk of developing any cancer (HR, 0.67 [95% CI, 60-74]) and obesity-associated cancer (HR, 0.59 [95% CI, 0.51-0.69]) compared with a matched control group during a mean follow-up of 3.5 years.10
Data on the association between losing weight and cancer-related mortality are limited. The only available study compared 6596 patients in Utah who had the RYGB procedure (1984-2002) and 9442 patients in a control group matched for 3 baseline factors (sex, age, and BMI category).11 Cancer-related mortality was lower in the surgery group compared with the control group (HR, 0.54 [95% CI, 0.37-0.78]).11 The limitations of the Utah study included absence of matching based on baseline health status associated with cancer risk (eg, smoking history or hormone therapy) and lack of follow-up weight changes.11
The mechanisms of excess cancer risk in patients with obesity are not completely understood. In genetically susceptible individuals, excess adiposity may accelerate cancer development by inducing chronic inflammation, increased release of sex-steroid hormones and adipokines, and insulin resistance with associated hyperinsulinemia.2,3,25,26 Bariatric surgery has been shown to attenuate excess inflammation, hyperinsulinemia, and modulate both sex hormones and adipokine levels.26-30 The mechanisms responsible for reduced cancer risk after bariatric surgery require further study.
Among all cancer types, endometrial cancer has the strongest association with obesity.2-4 The current study found that bariatric surgery was associated with a significant reduction in risk of endometrial cancer. Although the association between bariatric surgery and lower risk of different cancer types has been reported in prior studies,10,12-14 in the SOS trial31 and in the study performed in Utah,11 consistent with the findings from the current SPLENDID study, endometrial cancer was the only cancer type that had a significantly lower incidence after surgery compared with the nonsurgical control group (HRs, 0.56 and 0.22, respectively). A study in 72 women with severe obesity, for whom endometrial biopsies were examined before and after bariatric surgery, showed a significant reduction in the markers of endometrial proliferation and oncogenic signaling after surgery.26
In current practice, the 2 most common bariatric procedures are SG and RYGB. Although the extent of weight loss is comparable between the 2 procedures, they have different physiological effects. A large part of the stomach is removed with SG, whereas the gastrointestinal tract is re-routed with RYGB. Overlap of Kaplan-Meier curves for RYGB and SG (Figure 2B) suggests that losing weight itself, not procedure-specific physiological changes related to anatomical alterations, could be the principal mechanism for reduced risk of obesity-associated cancer.
In the current study and in other studies, substantial weight loss was required to observe a meaningful reduction in the cancer risk in a dose-dependent response30 (Figure 4B) and the separation of the Kaplan-Meier curves for incident obesity-associated cancer was only observed 6 years after the index date (Figure 2A).31 Currently, bariatric surgery is the only available treatment that can provide this magnitude and durability of weight loss. In an observational single-group study30 of 2107 patients who underwent bariatric surgery, 82 new cancer cases were diagnosed after a median follow-up of 5.5 years. Patients who lost greater than 20% of their total weight were at a significantly reduced risk of cancer compared with those who lost less than 20%.30 In contrast, other studies did not find an association between the extent of weight loss and the risk of obesity-associated cancer.9,32 Look AHEAD (Action for Health in Diabetes)1 is the only available randomized clinical trial that has examined long-term cancer outcomes after a nonsurgical weight loss intervention. Among nearly 5000 participants, an intensive lifestyle intervention led to only modest weight loss (8.6% vs 0.7% at 1 year; 6.5% vs 4.6% at 12 years).1 The difference in weight loss was not large enough to statistically mitigate the risk of obesity-associated cancer (HR, 0.84 [95% CI, 0.68-1.04]) or cancer-related mortality (HR, 0.92 [95% CI, 0.68-1.25]).1
Conclusions
Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.
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