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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Reference:
1. Nickel JC: Prostatic inflammation in benign prostatic hyperplasiadthe third component? Can J Urol 1994; 1: 1.
2. 2. Andriole GL, Bostwick DG, Brawley OW et al: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010; 362: 1192.
3. 3. Nickel JC, Roehrborn CG, O’Leary MP et al: The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol 2008; 54: 1379.
4. Tuncel A, Uzun B, Eruyar T et al: Do prostatic infarction, prostatic inflammation and prostate morphology play a role in acute urinary retention? Eur Urol 2005; 48: 277.
5. Mishra VC, Allen DJ, Nicolaou C et al: Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia? BJU Int 2007; 100: 327.
6. Kwon YK, Choe MS, Seo KW et al: The effect of intraprostatic chronic inflammation on benign prostatic hyperplasia treatment. Korean J Urol 2010; 51: 266
1. Nickel JC: Prostatic inflammation in benign prostatic hyperplasiadthe third component? Can J Urol 1994; 1: 1.
2. 2. Andriole GL, Bostwick DG, Brawley OW et al: Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010; 362: 1192.
3. 3. Nickel JC, Roehrborn CG, O’Leary MP et al: The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol 2008; 54: 1379.
4. Tuncel A, Uzun B, Eruyar T et al: Do prostatic infarction, prostatic inflammation and prostate morphology play a role in acute urinary retention? Eur Urol 2005; 48: 277.
5. Mishra VC, Allen DJ, Nicolaou C et al: Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia? BJU Int 2007; 100: 327.
6. Kwon YK, Choe MS, Seo KW et al: The effect of intraprostatic chronic inflammation on benign prostatic hyperplasia treatment. Korean J Urol 2010; 51: 266