'Obesity Paradox' in Colorectal Cancer: Is It Real?

Roxanne Nelson, BSN, RN

June 01, 2016

Excess weight has been identified as a risk factor for many types of cancer, but being overweight at diagnosis could also help some patients survive longer.

New findings show that, at least for colorectal cancer, patients who were overweight consistently had the best prognosis, with the lowest risks for both disease-specific and all-cause mortality.

In fact, risks were lowest in patients with a body mass index (BMI) of 28 kg/m². However, the risk for death was higher in patients who were obese (BMI ≥ 35 kg/m²) than in those who were normal weight, and higher in patients who were underweight. This phenomenon is known as the obesity paradox.

The study was published online May 19 in JAMA Oncology.

The main clinical message is that although strong scientific evidence shows that exercise in cancer patients should be encouraged, recommendations for weight loss among colorectal cancer patients are unwarranted after their diagnosis, explained lead author Candyce H. Kroenke, ScD, research scientist with the Kaiser Permanente Division of Research in Oakland, California.

"There is no evidence that overweight patients, as measured by BMI, should be encouraged to lose weight in the postdiagnosis period," she told Medscape Medical News.

However, it is not clear how long the protective effect of excess weight lasts in the postdiagnosis period, or at what point a patient should be encouraged to lose weight.

"Whether or when there might be an increase in risk with greater time from diagnosis" needs to be assessed, said Dr Kroenke. "We did not specifically examine this question."

"However, given the time frame of the study, it seems reasonable to say that in the first couple of years, concerns about weight should not be the focus," she added.

Contrasting Effects

Previous studies have shown that being overweight can have varying effects on prognosis, depending on cancer site. For example, obesity is an independent prognostic factor for mortality and the development of distant metastases after a diagnosis of breast cancer, as reported by Medscape Medical News.

In contrast, excess weight is associated with higher overall survival and longer time to treatment failure in patients with renal cell carcinoma, despite an increase in the risk for disease development.

However, being overweight or obese increases the risk for many diseases, including cancer.

Excess Weight Improves Survival

For their study, Dr Kroenke and her colleagues conducted a retrospective analysis of the electronic medical records of 3408 adults treated through Kaiser Permanente in Northern California who were diagnosed with stage I to III colorectal cancer from 2006 to 2011.

The team compared mortality risk at the time of diagnosis among weight groups.

Patients who were underweight or who were obese (class II or III) had a higher risk for mortality than those who were low-normal weight. Overall, associations for colorectal-specific mortality were similar to those for all-cause mortality.

However, 15 months after diagnosis, mortality risk was significantly lower in class I obese patients than in those low-normal weight patients (hazard ratio [HR], 0.56), and class II or III obese patients no longer had a higher mortality risk (HR, 0.84) (in fact, it was possibly lower).

Obesity Paradox Real?

Do these data mean that the obesity paradox is a real phenomenon?

"That depends on the analysis," explained Dr Kroenke. "In the analysis of postdiagnosis BMI, the risk in class II/III patients was not elevated."

"While there is some evidence of what is called the obesity paradox, the important point is that the association between BMI and mortality outcomes was nonlinear, with the lowest risk in the overweight patients," she pointed out.

The question of whether this phenomenon is real is explored by Andrew G. Renehan, PhD, FRCS, and Matthew Sperrin, PhD, both from the University of Manchester in the United Kingdom, in an accompanying editorial.

One possible explanation is that the seeming paradox reflects any one of a number of different methodologic issues, they write. But it is also possible that the paradox actually exists.

Before coming to the conclusion that the obesity paradox is a real association, they caution, there first has to be an exhaustive effort to exclude the many causes of confounding or biases.

This type of approach is crucial when interpreting the clinical implications, Drs Renehan and Sperrin emphasize.

For example, in cardiovascular literature, "some commentators have rushed to (mis)interpret that the obesity paradox is a true causal association, believing that 'the optimum body weight is shifting to a higher BMI range, once a chronic disease of some kind is present'," they write.

The editorialists "urge extreme caution."

"Although we appreciate that the interpretation of the association between BMI and mortality in patients with cancer is considerably more challenging than that between BMI and incidence cancer risk, we have a duty to appropriately convey this complexity to our patients and populations," they conclude.

The study was supported by the National Cancer Institute at the National Institutes of Health. The authors and the editorialists have no disclosures.

JAMA Oncol. Published online May 19, 2016. Abstract, Editorial

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