Urology

Chronic prostate inflammation is associated with severity and progression of benign prostatic hyperplasia, lower urinary tract symptoms and risk of acute urinary retention

Nickel JC, Roehrborn CG, Castro-Santamaria R, Freedland SJ, Moreira DM. J Urol 2016; Epub 1 Jul 2016

Acute and chronic inflammation in placebo-treated participants of the REDUCE study

Histological prostate inflammation is associated with the progression of benign prostatic hyperplasia (BPH).1A recent analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study examined the association between acute and chronic inflammation and BPH-related parameters.1

The analysis included men who were randomised to placebo in the 4-year REDUCE study, who were followed-up every 6 months.1The investigators examined whether acute or chronic inflammation (according to baseline biopsies) was associated with parameters including lower urinary tract symptoms (LUTS), newly-acquired BPH/LUTS, progression of existing BPH/LUTS, prostate volume and acute urinary retention (AUR).1

The relationship between baseline inflammation and International Prostate Symptom Scores (IPSS) and prostate volume was examined using the students t test.1In addition, univariable analyses (using a log rank test) and both univariable and multivariable analyses (using the Cox proportional hazards model) were used to ascertain whether baseline inflammation was associated with newly developed BPH/LUTS symptoms.1

Results

Of 4,109 men randomised to placebo with baseline biopsy inflammation data, 641 (15.6%) had acute inflammation and 3,216 (78.3%) had chronic inflammation.1

Although acute inflammation at baseline was not related to IPSS at any time point, throughout the study interval the researchers observed that chronic inflammation was associated with a higher baseline IPSS score (by 0.6; p<0.001) and larger prostate volume (by 3.2 cc; p<0.001).1

The investigators noted that whilst chronic inflammation was associated with larger baseline prostate volumes and greater changes in prostate volume from baseline than acute inflammation, acute inflammation was associated with smaller and relatively consistent prostate volumes.1

Chronic inflammation was associated with an increased risk for larger prostate size compared to baseline during the 4-year study period.1

Development of BPH/LUTS

Men without BPH/LUTs at baseline (n=797) were included in the analysis of the development of BPH/LUTS.1Of these, 93 men developed BPH after a median follow-up time of 49.9 months; however, this was not associated with acute or chronic inflammation at baseline.1

Men who did meet the definition of BPH/LUTs at baseline (n=2,659) were also evaluated for progression.1Of these, 1,264 had progressed after a median follow-up time of 41.4 months.1 Progression was not associated with acute or chronic inflammation at baseline.1

It was not possible to predict development or progression of BPH/LUTS from baseline inflammation status.1

However, the severity of chronic inflammation at baseline was weakly associated with BPH progression, according to the results of a post-hoc analysis.1

A history of BPH/LUTs was reported in 2,659 men at baseline, of whom 221 developed AUR over a median follow-up time of 48.4 months.1The investigators found a small but clinically meaningful association (hazard ratio 1.6–1.8; p=0.001) between chronic inflammation at baseline and shorter time to the risk of AUR in participants with baseline BPH/LUTs, and in the placebo group as a whole.1

Conclusions

This was the largest and longest longitudinal study assessing the relationship between prostate inflammation and BPH end points.1

The study confirmed the predicted association between prostate inflammation and BPH in this population of men randomised to placebo in the REDUCE study.1Men with evidence of prostate inflammation at baseline had greater IPSS scores and prostate volume than men without inflammation.1In addition, chronic prostate inflammation at baseline predicted an increased prostate volume from baseline and risk of AUR during the study period.1

Overall, prostate inflammation was not associated with development or progression of BPH/LUTs; however, there was a link with severe of inflammation.1

The researchers highlighted that these results may only be applicable to men in the REDUCE study cohort, and not to men who are not at risk of prostate cancer.1

Report on: Chronic prostate inflammation is associated with severity and progression of benign prostatic hyperplasia, lower urinary tract symptoms and risk of acute urinary retention. Nickel JC, Roehrborn CG, Castro-Santamaria R, Freedland SJ, Moreira DM. J Urol 2016; Epub 1 Jul 2016.

Reference list

1. Nickel JC, Roehrborn CG, Castro-Santamaria R, Freedland SJ, Moreira DM. Chronic prostate inflammation is associated with severity and progression of benign prostatic hyperplasia, lower urinary tract symptoms and risk of acute urinary retention. To be published in J Urol; [Preprint] 2016.