New research, presented this month at the 2012 American Association for Cancer Research annual meeting, has found that overweight and obese men are significantly more likely to experience PSA failure following prostate cancer surgery. PSA failure is generally defined as a detectable PSA level following radical prostatectomy to remove the prostate tumour suggesting that the cancer has not been completely eliminated.
The research team used data from 119 men who were awaiting surgery for localized prostate cancer. The researchers classified the chances of 5-year treatment failure for each of the men as low, intermediate, or high, based on tumour stage, Gleason score, and pre-treatment PSA levels.
The researchers found that obese men were much more likely to have an intermediate or high chance of treatment failure compared to men of a normal weight. Compared to the lowest quartile for BMI, men in the highest quartile were 7.74 times more likely to have an intermediate or high risk of failure following surgery. The average BMI in the highest quartile was 37.
Even at lower BMI levels, the risk of treatment failure remained elevated. Compared to the lowest quartile, those in the second quartile for BMI were 3.51 times more likely to have intermediate or high risk tumours while those in the third quartile were 6.52 times more likely. The average BMI of the men in the second and third quartiles was 27.8 and 32.0 respectively.
According to lead researcher Vincent Freeman: “The association was not limited to obese men; even being just overweight based on BMI was associated with an increased risk for prostate cancer recurrence”.
There have been conflicting results as to whether obesity increases the risk of developing prostate cancer however epidemiological studies on obesity and the risk of dying from prostate cancer have been much more consistent with obesity increasing the risk of prostate cancer death by 20 to 40%. This suggests that while obesity may not be a risk factor for prostate cancer, it is associated with more aggressive prostate cancers and a poorer prognosis.
A 2006 study, conducted by researchers from the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, found that obese men (BMI > 30) were 18% less likely to develop low grade prostate cancer but 29% more likely to develop high grade prostate cancer than men of a normal weight.
A 2011 study published in the International Journal of Cancer found no link between BMI and the overall incidence of prostate cancer however every 5 point increase in BMI increased the risk of aggressive prostate cancer and death from prostate cancer by 27% and 49% respectively.
Several mechanisms could explain the link between obesity and reduced prostate cancer survival. First, obese men also have larger prostates which can make it difficult to detect small tumours. PSA screening also tends to produce less accurate results in obese men. Combined, these factors make early detection of prostate cancer more difficult leading to a larger proportion of advanced prostate cancers in obese men.
Obese men also have higher insulin levels than normal weight men which results in higher serum levels of insulin-like growth factor-1 (IGF-1). In vitro studies have shown that IGF-1 is a powerful promoter of both androgen-independent and androgen-receptive prostate tumours.
Finally obese individuals tend to have higher circulating levels of the hormone leptin and lower levels of adiponectin. A high leptin to adiponectin ratio has been linked to the progression of several forms of cancer including post-menopausal breast cancer and prostate cancer.
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