At first, the headline is surprising, evening shocking: “Obesity Linked to Lower Death Risk in Non-metastatic CRPC[i] (castration resistant prostate cancer).” Does this news report mean that for men with advanced (but not metastatic) prostate cancer that no longer responds to hormones, being fat extends life?
This does not seem to make sense. A decade ago, a Columbia University doctor, Xavier Pi-Sunyer, issued a strongly worded paper on the medical risks of obesity:
Obesity is a significant risk factor for and contributor to increased morbidity [disease] and mortality [death], most importantly from cardiovascular disease (CVD) and diabetes, but also from cancer and chronic diseases, including osteoarthritis, liver and kidney disease, sleep apnea, and depression… Obesity is also strongly associated with an increased risk of all-cause mortality as well as cardiovascular and cancer mortality.[ii]
His statement sums up what the medical world has tried to pound into our heads: lose those extra pounds and live healthier longer! Dr. Pi-Sunyer supports this in stating that obesity is “strongly associated” with higher chances of cancer mortality. I have previously blogged about the link between obesity and the risk of developing aggressive PCa, based on research suggesting that when overweight men develop PCa, it may be a more dangerous type than if they were normal weight.
Before turning to the study, let’s define terms:
- Obesity – A general rule of thumb to determine obesity is Body Mass Index (BMI), a ratio of your weight to height. Using BMI, 18.5 to less than 25 is considered normal, 25 to less than 30 is overweight, and 30 or above is obese.
- Castrate resistant prostate cancer (CRPC) – Advanced prostate cancer that does not respond to androgen deprivation therapy (ADT) designed to deprive the cancer cells of testosterone. ADT stops the cancer in its tracks but it is not curative. Eventually the disease “outsmarts” the treatment. At this point, it has become castration resistant
- Non-metastatic CRPC – When a PCa patient on ADT experiences a rising PSA, that is the usually the first sign that hormone therapy is no longer effective. Tests and scans are then done to detect if new tumors are growing somewhere in the body (metastasis or PCa spread). If there is no evidence of this, it is called non-metastatic CRPC. However, the patient will be carefully monitored, and periodically re-scanned/tested if PSA continues to rise, with the assumption that eventually a new tumor will be detectable.
What did the study say?
The newly published study by Vidal, et al. (2018)[iii] examined the records of 1192 cases of men diagnosed with non-metastatic CRPC. Using BMI as a measure, they categorized them into groups:
- Underweight (BMI less than 21) – 4% of cases
- Normal weight (BMI 21 to 24.9) – 25% of cases
- Overweight (BMI 25-29.9) – 39% of cases
- Obese (BMI 30+) – 37% of cases
Bottom line: they found that obesity was linked with a 21% lower risk of all-cause mortality compared with normal weight. However, there was no association between obesity and the risk of prostate cancer specific mortality or metastasis.
According to the above-mentioned news report, “The authors noted that it is well established that obesity is associated with aggressive PCa and worse long-term outcomes among men with localized PCa, and a few studies have evaluated the link between BMI and PCa outcomes among men with metastatic CRPC. The current study… is the first to investigate PCa outcomes among patients with non-metastatic CRPC.”
Does obesity offer some kind of protection for this type of cancer?
At one level, this study isn’t entirely unheard-of. There are other studies suggesting that being overweight may offer a survival advantage, but this is debatable. Tobias and Hu (2013) believe that such findings involved methodological biases and limitations.[iv] For example, it’s possible that low BMI (underweight and even the low end of normal weight) may be the product of an existing poor health condition such as smoking, such that these cases would be more prone to early death.
There are also different kinds of fat, and some carry more risk of all-cause death than others. “Apple-shaped” people with belly fat are at higher mortality risk than “pear-shaped” people with hip and thigh fat. Brown fat is good, white fat not so much. So simply using BMI doesn’t tell us much about how each person’s fat ratio is composed. Also, simply using a BMI of 30+ to indicate obesity misses a key differentiation: according to one study, BMI of 35 or higher puts obese people at very high risk of death, whereas those at the lower end of obesity (BMI 30-34.9) are “not more likely to die than normal-weight people.”[v]
There are other theories: extra fat may mean extra survival resources during chronic diseases that drain the body of its own life support, such as metastatic cancer. Also, once patients are diagnosed with cancer, they tend to receive much more medical attention, which may increase their over survival odds since they are simultaneously being checked for blood pressure, cholesterol, etc. in the process of being monitored for their cancer. This may account for obese cancer patients outliving their obese peers who don’t have cancer.
Finally, the Vidal study occupies a unique place in the prostate cancer literature because their study population is not one that is usually correlated with obesity, those with non-metastatic CRPC. It bears pointing out, however, that just because metastasis was not detected does not mean it isn’t present. For prostate cancer patients, a new molecular type of imaging called PSMA PET/CT appears to be able to detect microscopic PCa metastasis almost anywhere in the body. This is not to devalue the findings of the Vidal paper, but to at least question whether distinguishing non-metastatic from metastatic CRPC is important.
An important conclusion
What can we take away from this study? Well, until there is expert commentary on the statistical methods used by the authors, we must assume that the correlation they found between BMI above 30 and lowered risk of death for this population is valid. The truth is, we don’t yet have a satisfying biological explanation, and so more research is needed.
However, in no way does this study encourage irresponsible eating habits. In the big picture, there are so many known risk factors and complications due to obesity that the vast preponderance of data shows that it is a known factor in heart disease, diabetes, joint problems, increased chance of aggressive cancers, and many more unpleasant, unhealthy and undesirable conditions.
So whether or not you have prostate cancer, don’t run out and have a fast-food French fries fest, or stock up on ice cream. Play it safe and do what the doctor says: shed those extra pounds.
[i] Jody Charnow. “Obesity linked to lower death risk in non-metastatic CRPC.” Renal & Urology News, Apr. 30, 2018. https://www.renalandurologynews.com/prostate-cancer/obesity-tied-to-lower-death-risk-in-non-metastatic-castration-resistant-prostate-cancer/article/761971/
[ii] Pi-Sunyer X. The medical risks of obesity. Postgrad Med. 2009 Nov; 121(6): 21–33.
[iii] Vidal AC, Howard LE, de Hoedt A, Kane CJ et al. Obese patients with castration-resistant prostate cancer may be at a lower risk of all-cause mortality: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int. 2018 Mar 9.
[iv] Tobias D, Hu F. Does being overweight really reduce mortality? Obesity (Silver Spring). 2013 Sep; 21(9): 1746–1749.
[v] Pam Belluck. “Study suggests lower mortality risk for people deemed to be overweight.” New York Times, Jan. 1, 2013. https://www.nytimes.com/2013/01/02/health/study-suggests-lower-death-risk-for-the-overweight.html