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Excess body weight, as measured by BMI, is associated with improved overall survival (OS) in men with advanced prostate cancer, particularly those with metastatic castration-resistant disease, a meta-analysis has found.

The researchers cautioned that their findings should not be interpreted as an endorsement of obesity but rather as evidence for the necessity of a nuanced approach to weight management in advanced prostate cancer that considers the potential risks associated with being underweight.

The study, with first author Feilun Cui, MD, PhD, Department of Urology, Affiliated Taizhou Second People’s Hospital of Yangzhou University in Taizhou, China, was published online in the International Journal of Obesity.

The ‘Obesity Paradox’

Obesity is a known risk factor for many cancers and for worse outcomes, but earlier research into the association between prostate cancer survival and overweight or obesity offers conflicting evidence. Some studies suggest excess weight confers a survival benefit — what’s known as the “obesity paradox” — while others found no difference or worse outcomes among patients with overweight/obesity.

To help clarify what the association may be, researchers in China pooled data from 15 studies that included 18,280 patients with metastatic prostate cancer. All of them compared OS between normal-weight men and those who were overweight (BMI, 25-29.9) or obese (BMI, ≥ 30).

Men with metastatic prostate cancer and overweight/obesity had a 21% lower risk of dying than normal-weight peers, with an overall pooled adjusted hazard ratio (aHR) for OS of 0.79.

When analyzed separately, the pooled aHR for OS was 0.81 in patients with overweight and 0.78 in patients with obesity, both indicating a significant survival benefit.

The association of overweight and obesity with OS was even stronger in men with metastatic castration-resistant prostate cancer (pooled aHR, 0.78 and 0.73, respectively), “indicating a stronger protective effect in advanced disease stages,” wrote the researchers.

Further analysis revealed a dose-response relationship: For every 1-unit increase in BMI, OS improved by about 4%.

Possible Explanations

The obesity paradox in prostate cancer could indicate that cancers arising in the context of obesity could have distinct biologic characteristics or that obesity accelerates the disease course, enabling earlier detection and treatment, the researchers wrote.

The survival advantage associated with overweight and obesity also could be partially attributed to the absence of cachexia — involuntary weight loss and muscle wasting that is a well-established predictor of poor survival in advanced malignancies — “suggesting that maintaining nutritional status is critical for patients with metastatic prostate cancer,” they added.

Another possible explanation could be that the increased adiposity and weight gain often caused by androgen deprivation therapy, a key treatment for metastatic prostate cancer, may help patients better withstand the metabolic stress of cancer and its treatments, the researchers wrote.

Their meta-analysis has some limitations, the researchers noted, including the retrospective nature of the studies involved, which raises the risk for selection bias and unmeasured confounding. There also was considerable variability in study designs, BMI definitions, and adjustments for clinical factors, as well as a lack of data on body composition.

“Future research should prioritize well-designed prospective studies to clarify the causal relationship between obesity and survival in metastatic prostate cancer,” the researchers wrote.

The study had no commercial funding. The authors reported having no relevant conflicts of interest.