Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity

Abstract

IMPORTANCE Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk.OBJECTIVE To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity. DESIGN, SETTING, AND PARTICIPANTSIn the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021.EXPOSURES Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265).MAIN OUTCOMES AND MEASURES Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality. RESULTSThe study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P = .002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P = .01).CONCLUSIONS AND RELEVANCE 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.

Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery

“…Important retrospective work has shown that patients who underwent bariatric surgery had reduced risk of both pre-menopausal and post-menopausal breast cancer with a 64% reduced risk in pre-menopausal ER-tumors, typically the most aggressive tumors with the worst outcomes ( Feigelson et al, 2020 ). Furthermore, reduced recurrence and mortality from cancer have been observed in bariatric surgery patients ( Aminian et al, 2022 ; Bruno and Berger, 2020 ; Zhang et al, 2020a ) although underlying mechanisms remain unclear. A major question remains regarding whether reductions in cancer risk and outcomes are associated with weight loss per se or are due to bariatric surgery-specific benefits, which are inherently challenging to delineate in patients ( Schauer et al, 2017 ; Alvarez et al, 2018 ).…”

“…Patients who receive a VSG have a reduction of 57% excess weight after 2 years, which remains relatively stable out to 10 years post-surgery ( O’Brien et al, 2019 ). Remarkably, patients who undergo surgically induced weight loss have a reduction in all-cause mortality up to 60% ( Syn et al, 2021 ; Doumouras et al, 2020 ; Aminian et al, 2022 ). Despite promising benefits of weight loss, weight loss regimens are not yet widely adopted in cancer prevention, survivorship, or therapy.…”

“…Our premise is that obese subjects are exposed to chronic inflammation that leads to increased risk of cancer yet induces compensatory immunosuppressive mechanisms or does not achieve a sufficient inflammatory threshold to protect from cancer initiation in a failure of protective immunity. Importantly, bariatric surgery is protective against subsequent risk of developing any cancer by 10–33% ( Aminian et al, 2022 ; Zhang et al, 2020b ). Feigelson et al, 2020 described the greatest benefit in pre-menopausal estrogen receptor negative cancer in patients after bariatric surgery.…”

The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer

“…Considerable evidence from retrospective and prospective cohort studies supports a decreased risk of endometrial cancer in patients with obesity who undergo bariatric surgery compared with nonsurgical matched controls ( 52 , 53 , 67 , 70 – 72 ). A prospective pilot study of the effects of bariatric surgery on the risk of endometrial pathology in women undergoing laparoscopic RYGB identified a 6.8% preoperative prevalence of occult hyperplastic endometrium, considered a precursor lesion for endometrial cancer, upon biopsy.…”

Obesity and cancer

“…Bariatric surgery achieves significant and long term weight loss and appears to be effective in reducing the risks of certain cancers. In the recently published SPLEN-DID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) cohort study, greater weight loss from bariatric surgery reduced obesity-associated cancer incidence in a dose-dependent manner [10]. However, from a global perspective, access to bariatric surgery is limited to a small fraction of the population, therefore may not be a feasible strategy to greatly reduce obesity-associated cancers worldwide.…”