Saturday, April 9, 2011

Prostate Cancer and Obesity: A Deadly Combination

After I diagnose a patient with prostate cancer, we often have a lengthy discussion about treatment options and prognosis for the disease.  Many patients have a great mentality and express the desire to fight the cancer in any way possible.  Invariably, I hear a recurring question from these patients: “Doc, what can I do to increase my odds of beating this thing?”  If they are overweight or obese, I answer very emphatically, “Lose some weight.” 

Obesity is becoming an all too common phenomenon worldwide.  In the United States approximately 50% of men are considered overweight and 30% of men are considered obese.  Obesity is usually determined through a calculation of the Body Mass Index (BMI) which is weight in kilograms divided by height in meters squared.  Overweight men are classified as those with a BMI over 25 while obese men have a BMI greater than 30.  This excess weight exerts a tremendous toll on health by contributing to heart disease, diabetes, and hypertension.  Studies have demonstrated that men who are considered obese have a 50-100% higher chance of dying than men who are considered normal weight.  While we all know that obesity is a major risk factor for heart disease and some related illnesses, what does this have to do with prostate cancer?  Well, studies have also shown that men who are obese have a 40-80% higher risk of getting cancer (nonspecific) than those men that are considered to have a normal weight.  One of the cancers that has been greatly studied in the context of obesity is prostate cancer. 

While there has been no definitive proof of how obesity affects prostate cancer, numerous theories have been described.  First, studies have postulated that obesity affects prostate cancer through it impact on sex steroids within the body.  Fat in the body converts circulating testosterone to estrogen.  While testosterone is basically the “food” of prostate cancer, studies have shown that men undergoing surgery for prostate cancer have a higher risk of advanced stage cancer if there testosterone values are low. In addition, other studies have demonstrated that lower levels of blood testosterone actually correlate with a small but significant increase in the risk of prostate cancer.  All of this data seems to point to the fact that, by lowering testosterone levels in the bloodstream, excess body fat can actually predispose men to more aggressive prostate cancers.  Another theory of how fat and obesity impacts prostate cancer has to do with insulin like growth factor-1(IGF-1).  In obese men, high levels of IGF-1 are usually found in the bloodstream.  Laboratory studies have demonstrated that prostate cancer cells multiply more quickly in environments with higher levels of IGF-1.  In addition, clinical studies have shown significant correlations between IGF-1 and prostate cancer risk. 

While these theories are interesting, they do not really show us the true impact of obesity on prostate cancer.  Numerous clinical studies have evaluated the role of obesity in clinical prostate cancer.  The evidence linking obesity with the development of prostate cancer has been mixed.  While some studies have found a relationship between obesity and an increased risk of prostate cancer, others have shown no association.  Still other studies have actually demonstrated an inverse relationship, meaning that obesity was actually associated with a lower risk of developing prostate cancer.

Once prostate cancer has been diagnosed, however, there is no confusion as to the impact of obesity.  Multiple studies have demonstrated that obese men appear to have pathologically more aggressive cancer in terms of higher Gleason scores.  In addition, surgery to treat prostate cancer has been found to result in significantly higher rates of positive surgical margins in obese men.  Positive surgical margins are noted when the removed prostate gland is examined under the microscope by the pathologist after surgery.  A pathology report consistent with positive margins means that prostate cancer cells were seen at the cut edge of the removed prostate gland, meaning that the surgeon cut across some cancer when removing the prostate and that some cancer has been left behind.  Many studies have attributed this higher rate of positive margins to the fact that the body habitus of an obese man makes surgery more technically challenging.  As a result, more bleeding can occur, making visualization more difficult and positive margins more likely.  Given this theory, some have argued that robotic surgery, which enhances visualization and minimizes bleeding, should lead to better margins in obese men.  However, at least one large study, which divided patients into open versus laparoscopic surgery groups, still demonstrated a higher rate of positive margins in obese men, regardless of surgery type undertaken.

Obesity has been demonstrated to have perhaps its most significant impact on prostate cancer recurrence after surgery.  Most studies have been in agreement that obese men are substantially more likely to have a PSA recurrence (consistent with cancer recurrence) after prostatectomy as compared to those men that are of normal weight.  One large study actually demonstrated that moderately to severely obese men are 2.5- 3 times more likely to have a PSA recurrence as compared with their non-obese counterparts.  This finding is even more astounding in that it accounts for other factors that can affect cancer recurrence like preoperative PSA and Gleason score, stage, positive margins, and lymph node status.  An interesting study from Johns Hopkins published this year evaluated the effects of weight gain on men undergoing prostate cancer surgery.  The study found that men who gained approximately 5 pounds (2.2 kg to be exact) during the period of time starting 5 years prior to surgery and continuing to 1 year post surgery had twice the likelihood of  a PSA recurrence after surgery as compared to those men who maintained a steady weight.  Not surprisingly, with its impact on surgical outcomes and PSA recurrence, obesity has also been uniformly associated with an increased risk of prostate cancer mortality

I think the take home message of this post is fairly obvious.  If you have prostate cancer, probably the most important, proactive thing you can do (aside from getting treatment) is making sure to control your weight.  Find out what your BMI is from your doctor or calculate it online.  If you fall into the obese category, lose some weight.  Studies have shown that the very process of exercise can help men with prostate cancer.  A healthy, low fat diet has also demonstrated significant benefits.  Even if all of this data is wrong and you don’t benefit from escaping obesity from a prostate cancer standpoint, there is overwhelming evidence that you would benefit from the standpoint of your heart.  On that note, I want to share 1 more statistic.  The Prostate Cancer Prevention Trial followed 18,000 men for 7 years to study the impact of a drug called Finasteride on prostate cancer.  During the study, a total of 10 men died of prostate cancer.  During the same time period, 1123 men died of other causes, most of which were related to heart disease. Is that not enough of a reason to lose a little weight?

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  1. Most of us thought eating diet high in Omega 3s and low in "bad" fats would help reduce risk of prostate cancer, and of advanced prostate cancer. Now we see this, from a very reputable institution:

    What do you make of this? Would it cause you to advise someone who is concerned about prostate cancer to stop taking Omega 3 supplements? To eat less fatty fish? To go have an ice cream, or trade the egg beaters for a few real eggs?

    I found the results of this really surprising.

  2. Chamorgadol: Taking epidemiologic studies like this too seriously can be dangerous. They are not controlled and so are prone to confounding factors not accounted for during the study like family history or other lifestyle factors. Omega 3 fatty acids are excellent for heart health and some studies have demonstrated them to be helpful with prostate cancer as well. I hope that this study does not deter men from eating fish regularly at least until better, randomized and controlled studies are completed.