Chronic Inflammation in Benign Prostate Tissue Is Associated With Aggressive Prostate Cancer
An analysis of prostate tissue biopsies collected from participants in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) has 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 an aggressive disease, compared with those whose benign prostate tissue had no inflammation. The study findings are published in Cancer Epidemiology, Biomarkers & Prevention.
The study was conducted to determine whether finasteride prevents prostate cancer. To be eligible to enroll in the study, men had to be at least 55 years old and have a normal digital rectal examination with a serum PSA of 3 ng/mL or less. From 1993 to 1997, 18,882 men enrolled in the trial. The men were randomly assigned to receive finasteride (5 mg/d) or placebo for 7 years. All participants completed questionnaires on demographics, lifestyle, and medical factors, including cigarette smoking history, first-degree family history of prostate cancer, and history of a diagnosis of diabetes. Weight and height were measured, and body mass index (BMI) was calculated and recorded.
Study Methods
The study researchers screened all participants for prostate cancer by PSA and digital rectal examination during annual visits. If serum PSA concentration was > 4 ng/mL or the digital rectal examination was abnormal, a prostate biopsy was recommended. Cancers detected on those biopsies were considered to be “for-cause” biopsy detected. Those participants who did not have prostate cancer diagnosed during the trial were requested to undergo an end-of-study prostate biopsy.
From the placebo arm of the study, the researchers sampled 191 prostate cancer cases and 209 frequency-matched controls for whom biopsy tissue was available. Histopathologic evaluations of the biopsy samples were performed to identify the prevalence and extent of inflammation and the types of inflammation (acute or chronic).
Significant Association Found
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 the 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 BMI, cigarette smoking pack-years, and history of diabetes.
The association remained even among men whose PSA levels were less than 2 ng/mL. 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 any inflammation.
“Our finding that inflammation, primarily chronic, in benign prostate tissue is associated with an increased odds of prostate cancer, and high-grade prostate cancer in particular, will inform the etiology of this disease,” wrote the study authors. “Identifying those men at highest risk of developing aggressive disease is the first step in being able to prevent lethal prostate cancer. Rather than targeting interventions to all healthy men, which may result in unintended harms, if causal, the findings from our work may allow preventive interventions to be targeted to those men who would benefit the most.”
Elizabeth A. Platz, ScD, MPH, of Johns Hopkins Bloomberg School of Public Health, and Angelo M. De Marzo, MD, PhD, of Johns Hopkins School of Medicine, are the corresponding authors for the Cancer Epidemiology, Biomarkers & Prevention article.
The study was funded by the National Cancer Institute. Study author Charles G. Drake, MD, PhD, is a consultant/advisory board member of Bristol-Myers Squibb and Compugen. William G. Nelson, MD, PhD, is a consultant/advisory board member of GlaxoSmithKline. The other study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
