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Chronic Inflammation May Be Linked to Aggressive Prostate Cancer

Researchers find connection even among men with low PSA levels

The presence of chronic inflammation in benign prostate tissue was associated with high-grade (aggressive) prostate cancer, and this association was found even in men with low prostate-specific antigen (PSA) levels, according to a new study published in Cancer Epidemiology, Biomarkers & Prevention.

An analysis of prostate tissue biopsy samples collected from participants in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) found that those whose benign prostate tissue had chronic inflammation had 1.78 times higher odds of having prostate cancer, and 2.24 times higher odds of having aggressive disease (characterized by a Gleason sum of 7 to 10), compared with those whose benign prostate tissue had no inflammation.

“We found that men who had at least one biopsy core with inflammation had a higher likelihood of having high-grade prostate cancer compared with those who did not have any inflammation in their biopsy tissue,” said lead investigator Elizabeth A. Platz, ScD, MPH. “While we know that inflammation is common in prostate tissue from men who have some indication to prompt a biopsy, such as high PSA or an abnormal digital rectal examination [DRE], we were surprised to find that the prevalence of chronic inflammation in the men who didn’t have any such indication was really high, about 78%.”

Between 1993 and 1997, 18,882 men who were at least 55 years old and had a normal DRE with a serum PSA of 3 ng/mL or less were recruited into the PCPT. All of the participants completed questionnaires, which included demographic characteristics, lifestyle, and medical factors, and were followed for 7 years after they were randomly assigned to receive either finasteride or placebo.

The investigators screened all of the participants for prostate cancer by PSA and DRE during annual visits. Those with an indication underwent a “for-cause” biopsy if they had cancer, and those who did not have prostate cancer diagnosed during the trial were recommended to undergo a biopsy at the end of the trial even if they did not have an indication.

From the placebo arm of this study, Platz and her colleagues sampled 191 prostate cancer cases and 209 frequency-matched controls for which biopsy tissue was available. They performed histopathologic evaluation of the biopsy samples to identify the prevalence and extent of inflammation as well as the type of inflammation (i.e., acute or chronic).

The researchers found that 86.2% of cases and 78.2% of controls had at least one biopsy core with inflammation, most of which was chronic, and this difference was statistically significant. They also found that the association between chronic inflammation and aggressive prostate cancer did not change after adjusting for known risk factors, including body mass index, pack-years of cigarettes smoked, and a history of diabetes. In addition, this association held true even among men whose PSA levels were less than 2 ng/mL.

“We detected chronic inflammation in prostate tissue of men who had prostate cancer but had PSA levels lower than 2 ng/mL, and thus our work supports an association between inflammation and prostate cancer that is not explained by PSA-associated detection bias,” Platz said.

Among men whose PSA levels were less than 2 ng/mL at the time of biopsy, those whose prostate tissue had inflammation had 4.11 times higher odds of having aggressive prostate cancer compared with those whose prostate tissue did not have inflammation.

“Our team is next studying the type of inflammatory cells that may be influencing the risk of aggressive prostate cancer,” Platz said.

Source: AACR; April 18, 2014.

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