From the Desk of the Editor: Meta-analysis of Metabolic Syndrome and Prostate Cancer

Metabolic syndrome is a constellation of conditions including obesity, diabetes, hypertension, and alterations in serum lipids. It was originally defined as a syndrome that is linked with increased risk of heart disease. As the obesity epidemic has swept through the Western world, the rates of metabolic syndrome have likewise risen dramatically. As many of the conditions that constitute the metabolic syndrome have individually been linked with cancer, there is growing interest in the role of the metabolic syndrome with cancer. 

Specifically, many papers have been published regarding the link between metabolic syndrome and prostate cancer, often with differing results.  In such a situation, (a lot of good studies exist, but with conflicting data), a meta-analysis, which combines the results from all the studies and synthesizes a single “answer” is a great choice to cut through the noise. Fortunately, such a meta-analysis was recently published.

Gacci et al performed a meta-analysis of 24 studies including over 130,000 men of whom 17% had metabolic syndrome. However, when reviewing individual studies, the prevalence of metabolic syndrome varied from ~3% to over 60% based upon geographic location, definition used, and year of study (more recent studies tended to have higher rates of metabolic syndrome).  For overall prostate cancer risk, the authors found that metabolic syndrome was linked with a modest 17% increased risk of prostate cancer.  However, as obesity and diabetes are associated with lower PSA levels, which can impair our ability to find prostate cancer, the authors importantly looked at other outcomes. When restricted to men with high-grade prostate cancer (Gleason grad 8 or higher; grade group 4 or 5), metabolic syndrome was associated with a quite high 89% increased risk.  Likewise, metabolic syndrome was linked with a 77% increased risk of biochemical recurrence after treatment.

What can we learn from this study?  We learned that metabolic syndrome is not a major risk factor for overall prostate cancer (17% is relatively modest).  However, in the era when prostate cancer is really two diseases – one that can be safely watched and is not life-threatening and one that needs treatment and is life-threatening, it appears that metabolic syndrome selectively influences the aggressive variant of prostate cancer – more high-grade disease and more recurrences after treatment.  This information opens up two paths: research and clinical. The fact that metabolic syndrome is linked with aggressive prostate cancer allows us to ask “why”?  What is it about metabolic syndrome?  Is it inflammation?  Insulin?  Cholesterol?  Other hormones?  Shared genetics that predispose to metabolic syndrome also predispose to prostate cancer?  Something else?  Beyond research, these findings may also have clinical implications.  While the data suggest that targeting and preventing the metabolic syndrome may be the perfect approach to prevent aggressive prostate cancer this requires prospective studies as well as to address when to intervene (once diagnosed is it too late?). However, given the overall adverse effects of metabolic syndrome, these data can be used as one more motivating factor to get men to lose weight, exercise, and by altering their lifestyle – hopefully lower their rate of aggressive prostate cancer.

Written by: Stephen J. Freedland, MD

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