Reduction in Melanoma After Bariatric Surgery ― Really?

Pam Harrison

October 30, 2019

Bariatric surgery and the weight loss that it induces are associated with a markedly reduced risk for skin cancer, including melanoma, according to a new analysis from the Swedish Obese Subjects (SOS) study.

In an earlier report from this study, Swedish researchers found that bariatric surgery was associated with a reduced risk for female-specific cancers, including breast, endometrial, ovarian, and all other gynecologic cancers.

Now, at a median follow-up of 18.1 years, the same research team has found that patients who underwent bariatric surgery had a 57% lower risk of developing melanoma and a 41% lower risk of developing squamous cell carcinoma compared to participants who received conventional obesity treatments.

"Obesity is an established risk factor for several cancer types, but the association between obesity and melanoma is inconclusive," Magdalena Taube, PhD, University of Gothenburg, Sweden, and colleagues observe.

"[Our] findings suggest that bariatric surgery is associated with a reduction in the incidence of skin cancer, including melanoma, in patients with obesity and that there may be an association between obesity and this cancer form," they state.

The study was published online October 30 in JAMA Dermatology.

However, a melanoma expert who was approached for comment was not impressed. Jeffrey Weber, MD, NYU Langone Medical Center, New York City, who regularly provides commentary for Medscape Medical News, emphasized that the study was not randomized. This of itself complicates the interpretation of any data regarding the incidence of melanoma, he told Medscape Medical News.

"The assessment of the incidence of melanoma was also not in any way adjusted for confounders that increase the risk of melanoma, like hair color, eye color, number of moles, or sun exposure history, which might have been quite imbalanced between the groups," he added in an email.

Weber also pointed out that there was no assessment of the association of melanoma incidence with weight loss after surgery or during observation, which would have supported the idea that obesity over time might be associated with melanoma risk.

"Finally, there was no accommodation of the idea that patients in the surgery group may have had more contact with the health system, have closer skin surveillance and [thus] a greater likelihood of having a premalignant lesion resected, leading to a lower melanoma and skin cancer incidence," Weber observed.

Weber also noted that the incidence of melanoma in this study was 50% of the incidence of skin cancer.

"This seems highly unlikely, since there are over 1,000,000 skin cancers diagnosed yearly in the US and about 100,000 melanomas," he observed.

"Thus, there are major unanswered issues with this work, which has to be interpreted with caution," Weber suggested.

Details of the Findings

The SOS study is an ongoing, prospective, matched intervention trial in which outcomes for those assigned to bariatric surgery are being compared to outcomes achieved with standard obesity management.

It is being conducted across 25 surgical departments and 480 primary healthcare centers in Sweden.

For the current analysis, Taube and colleagues included 4042 evaluable participants. The mean age of the participants was 47.9 years, and approximately 71% were women. On study enrollment, body mass index (BMI) was greater than 38 for women and greater than 34 for men.

About half of the group (n = 2007) underwent surgery. Of those patients, 13% underwent gastric bypass, 19% underwent banding, and approximately 68% underwent vertical banded gastroplasty.

The remainder (n = 2040) served as controls. They received conventional counseling for obesity management from their primary healthcare provider.

Two years after undergoing the surgical procedure, the mean weight loss among surgical participants was 28.7 kg; at 10 years' follow-up, the mean weight loss was 21.1 kg.

Fifteen years after undergoing surgery, recipients had lost 21.6 kg compared to baseline.

In contrast, "mean weight changes in the control group were small and never exceeded 3 kg in gain or loss," the researchers note.

Numbers of Skin Cancers and Melanoma Are Small

During the follow-up interval, the numbers of both squamous cell carcinomas and melanomas were small in both groups, the researchers acknowledge, but they point out that there were statistically significant differences between surgical participants and control patients.

For example, the cumulative incidence of skin cancer among control patients totaled 41 events, compared with 23 events for surgical patients.

In total, 16 squamous cell carcinomas were documented in the control group, vs 11 in the surgery group.

For melanoma alone, the cumulative incidence totaled 29 events over follow-up, compared with 12 events in the surgery group.

"On the basis of 29 malignant melanoma events in the control group and 12 in the surgery group, the incidence rates were 0.8 per 1000 person-years...in the control group and 0.3 per 1000 person-years...in the surgery group," the researchers point out.

In a pooled analysis of both squamous cell carcinoma and melanoma, the incidence rates for skin cancer were 1.2 per 1000 person-years in the control group, vs 0.7 per 1000 person-years in surgery group, the authors report.

"The number needed to treat to prevent 1 malignant melanoma event during 20 years with bariatric surgery was 106," the researchers state.

"And of importance, baseline BMI was not associated with the preventive effect of bariatric surgery on skin cancer incidence," they note.

Potential Explanations

The researchers suggest that the reduced incidence of skin cancer following bariatric surgery might be explained by alterations in patients' metabolic or endocrine milieu following surgery.

The authors point out that they previously reported that baseline insulin levels are associated with a reduction in the incidence of cancer in women who have undergone bariatric surgery, an effect that would also be at play in the current analysis.

Moreover, even though African Americans are protected against sun-damaging effects by melanin in their skin, the relative risk for melanoma is greater in obese African American men than in non-obese African American men, according to a large study of the US military.

"Thus, the relative melanoma risk in African American veterans with regard to obesity is similar in magnitude to the risk associated with a family history of melanoma," the authors point out.

"These results suggest that mechanisms besides sun exposure mediate the increased risk of melanoma in people with obesity," they observe.

A potential mechanism could involve the metabolic hormone leptin, which is upregulated in obesity and which is associated with lymph node metastasis in patients with melanoma.

Obesity also causes chronic inflammation, which could encourage tumor growth, they add.

Alpha-melanocyte-stimulating hormone has also been shown to reduce the expression of adhesion molecules on melanoma cells. Normally, these molecules stimulate immune cell interactions; when reduced, the ability of the immune system to detect tumor cells would be impaired.

More simply, the association between melanoma and bariatric surgery may reflect changes in physical activity made possible by the dramatic weight loss precipitated by bariatric surgery. Such weight loss may promote a more active lifestyle and thereby counter the heightened risk for cancer associated with a sedentary lifestyle, the authors comment.

The study was supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases, the Swedish Research Council, the Swedish state, and the Swedish Diabetes Foundation. Taube has disclosed no relevant financial relationships. Two coauthors report receiving personal fees from pharmaceutical companies, as detailed in the article. Weber has relationships with many pharmaceutical companies.

JAMA Dermatol. Published online October 30, 2019. Abstract

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