Bariatric surgery is associated with a lower risk for several obesity-related cancers, though the associations vary by cancer type, according to two recent analyses. Both analyses, however, were based on observational data, limiting conclusions about whether bariatric surgery itself can reduce the risk for cancer.

One paper — a position statement on metabolic and bariatric surgery and the risk for cancer that includes a systematic review and meta-analysis — found that bariatric surgery was associated with lower incidence of breast, endometrial, colorectal, and several other cancers among individuals with obesity, compared with no surgery. Associations were not statistically significant for some malignancies, including pancreatic, esophageal, and gastric cancers, while bariatric surgery was associated with a significantly higher incidence of prostate cancer.

Another analysis — an observational study of more than 780,000 patients in three Nordic countries — reported lower rates of liver, endometrial, and ovarian cancer in the bariatric surgery group, though higher rates of pancreatic cancer.

While a possible reduction of risk for cancer “may be discussed” with patients in the context of weight-loss surgery, the procedure “should not be offered solely for cancer prevention,” Amanda Belluzzi, MD, of Ospedale Santa Maria della Misericordia di Rovigo in Rovigo, Italy, and colleagues reported in the position statement from the International Federation for the Surgery and other Therapies for Obesity.

Overall, Belluzzi and colleagues rated the certainty of the evidence in their analysis of 26 observational studies as “low or very low.” The review found no randomized clinical trials, and the “risk of bias was judged to be serious for all outcomes, mainly due to the nonrandomized design, potential residual confounding, and selection bias,” the authors wrote.

However, the review had other notable limitations.

The estimates reported in the abstract and the paper did not all align. The main text reported pooled adjusted hazard ratios (HRs) of 0.88 for breast, 0.57 for endometrial, and 0.72 for colorectal cancer in favor of surgery. But the abstract reported different estimates for breast and endometrial cancer: incidence rate ratios of 0.85 and 0.38, respectively. The discrepancies were not reconciled in the paper or in the supplementary materials. Belluzzi did not respond to emails seeking comment.

The review also found that bariatric surgery was associated with a higher hazard of prostate cancer (adjusted HR, 1.56; 95% CI, 1.06-2.31), though the finding was based on only three studies and requires confirmation, the authors noted.

Matt Spick, PhD, a health-data scientist at the University of Surrey in Surrey, England, highlighted several other points of concern. The analysis lumped together comparisons of surgery vs no surgery, surgery vs drug and drug vs drug.

Various cancer types — such as breast, endometrial, ovarian, liver, pancreatic, esophageal, multiple myeloma, kidney, thyroid, gall bladder, and colorectal — included comparisons of semaglutide and tirzepatide users with DPP-4 inhibitor users, which Spick called “a ‘stop right there’ issue.” Combining these treatment comparisons into one pooled estimate makes it harder to interpret the result as evidence about bariatric surgery specifically.

Spick also noted that the work had been received by the journal on September 19, revised after just 3 days, and accepted on September 26, leaving little time for peer review.

“This is a complete mess of an analysis,” said Spick.

Jason Oke, DPhil, of the Centre for Evidence-Based Medicine at the University of Oxford in Oxford, UK, also noted that many of the studies in the review had relatively short follow-ups. “Many cancers develop over years or decades, yet a lot of cohorts have short follow-up (2-6 years), and the medication cohorts have even shorter follow-up,” Oke explained. “Would longer follow-up change this?”

Meanwhile, the Nordic cohort, a large population-based analysis, offers more support for an association between surgery and the risk for cancer, but still can’t establish cause-and-effect.

Cecilia Radkiewicz, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and colleagues analyzed prospectively collected data on more than 784,000 patients aged 18-59 years who had an obesity record in Denmark, Finland, or Sweden. Nearly 100,000 participants underwent bariatric surgery. After adjusting for age, sex, calendar year, country, and obesity- and lifestyle-related comorbidities, the incidence of obesity-related cancers overall was significantly lower in patients who had surgery than those who didn’t (adjusted incidence rate ratio [aIRR], 0.81; 95% CI, 0.77-0.85).

The most pronounced reductions were seen in liver (aIRR, 0.49; 95% CI, 0.34-0.70), endometrial (aIRR, 0.51; 95% CI, 0.45-0.59), and ovarian cancers (aIRR, 0.73; 95% CI, 0.60-0.87). The risk for pancreatic cancer, however, was higher following surgery (aIRR, 1.19; 95% CI, 1.002-1.41).

Age did not significantly modify the associations for any individual cancer site, except pancreatic cancer, with younger patients having higher excess risk for this malignancy (aIRR, 2.21; 95% CI, 1.44-3.39) than those aged 40-59 years (aIRR, 1.07; 95% CI, 0.89-1.29).

“These findings suggest that the long-term oncologic benefits of bariatric surgery apply broadly across age groups and sexes,” the researchers concluded.

While the analysis was large, it suffered from many of the same issues as earlier observational work, according to Gilbert Welch, MD, a cancer epidemiologist and general internist at Brigham and Women’s Hospital in Boston. “New study, but same problem,” he said.

The researchers acknowledged that the observational design could not rule out residual and unmeasured confounding. The registries lacked data on BMI, smoking, alcohol consumption, diet, and physical activity. Differences in medical monitoring could also have affected cancer detection, as patients who undergo surgery may receive more follow-up care.

Overall, “I would not be surprised to learn that bariatric surgery and/or GLP-1s are associated with fewer car accidents and higher recycling rates,” said Welch. “The reason to undergo these interventions is to lose weight.”

Regarding the position statement, flawed as it may be, the authors likely came to the “right conclusion,” Oke noted. “The evidence does not support [bariatric surgery] as (solely) a cancer-preventive intervention.”

Radkiewicz and several of the authors of the position statement declared financial ties to companies making or developing weight-loss drugs. Spick, Welch, and Oke reported no disclosures.