Chronic Prostate Inflammation is Associated with Severity and Progression of Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms and Risk of Acute Urinary Retention - Commentary

Previous data has suggested that histological inflammation of the prostate gland might be implicated in the etiology and pathogenesis of benign prostatic hyperplasia (BPH), along with static and dynamic factors known to cause benign prostatic enlargement (BPE) and associated lower urinary tract symptoms (LUTS).1 A previous trial called REDUCE revealed a relationship between degree of chronic inflammation and BPH/LUTS2, and it has been suggested that histological prostate inflammation may be associated with progression of clinical BPH.3 Other studies have demonstrated that prostate inflammation was more prevalent in patients with urinary retention compared to those with only LUTS4,5, and men with higher grade inflammation may be at greater risk for BPH related surgery.6 This studies examines the REDUCE study population, and evaluated associations between histological prostate inflammation, and the development and progression of BPH/LUTS in a 4-year period.

The REDUCE trial is a 4–year, phase 3, placebo controlled study to determine whether daily dutasteride 0.5mg reduces the risk of biopsy detectable in prostate cancer. The inclusion criteria for the REDUCE study were men: 50-75 years old, specific serum PSA ng/ml according to age, and a single negative 6 to 12-core prostate biopsy within 6 months of study enrollment. Once enrolled and consented, baseline biopsies were performed before the start of study, and patients were follow-up every 6 months to obtain data on peak urinary flow, PVR, I-PSS, and quality of life. In summary, the association of acute and chronic inflammation detected on baseline biopsies and BPH related parameters, such as I-PSS (International Prostate Symptom Score) and prostate volume, was analyzed. In addition, the associations of inflammation of newly developed BPH/LUTS and BPH progression in patients with existing benign prostatic hyperplasia/LUTS were also analyzed.

In total, 4109 men were included in the study. The results of the study showed that acute and chronic inflammation was seen in baseline negative biopsies of 641 and 3,216 men, respectively. Chronic baseline inflammation was associated with higher I-PSS at baseline, larger prostates at baseline, and larger prostate volume when compared to acute baseline inflammation, differences noted throughout the study interval. The presence of acute and chronic inflammation was not associated with the progression of BPH/LUTS on univariable or multivariable analysis. However, it was observed that chronic inflammation showed an association with more moderate inflammation with the progression of BPH/LUTS. Finally, chronic inflammation at baseline was associated with an increased risk of acute urinary retention.

The major limitation that the authors noted is that it was a cancer prevention study, yet the analysis was a post-hoc evaluation of BPH end points in the placebo group only. This would complicate any evaluation of the effect of baseline inflammation on BPH/LUTS progression. The strength in their analysis, however, was that it is the largest and longest longitudinal study evaluating the connection between inflammation and BPH end points. In conclusion, men with chronic prostate inflammation in the baseline biopsy had greater LUTS and prostate volume than men without prostate inflammation during the REDUCE trials. Chronic inflammation is associated with increased risks, and severity and the progression of BPH and LUTS outcomes.

Authors: J. Curtis Nickel, Claus G. Roehrborn, Ramiro Castro-Santamaria, Stephen J. Freedland and Daniel M. Moreira

Affiliations: Departments of Urology, Queen’s University, Kingston, Ontario, Canada, University of Texas Southwestern Medical Center, Dallas, Texas, and Mayo Clinic, Rochester, Minnesota, Global R&D Unit, GlaxoSmithKline, Inc., King of Prussia, Pennsylvania, and Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California

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