Although it was hypothesised >20 yr ago that prostatic inflammation could influence clinical presentation and possibly surgical outcome in patients with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), only more recently has compelling substantiating evidence become available.
To review the evidence for the role of inflammation in the clinical presentation and treatment of BPH/LUTS.
This article is based primarily on material presented at a satellite symposium entitled, “Inflammation and Prostatic Diseases: From Bench to Bedside,” held during the 2015 annual meeting of the European Association of Urology in Madrid, Spain. Current data regarding the link between inflammation and BPH were reviewed.
Studies such as the large-scale Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial and others have clearly demonstrated the association between the presence and/or degree of histologic inflammation and its impact on parameters such as prostate volume, voiding LUTS, and type of surgery required to treat BPH. Prostatic inflammation has been shown to increase by threefold the risk for acute urinary retention, an end point in the natural progression of BPH. Inflammation has been proposed as the common thread between the metabolic syndrome and BPH/LUTS, which frequently co-exist, and offers new therapeutic targets for medical treatment. Motivated patients can undertake lifestyle modifications (eg, weight, diet, exercise) to potentially prevent the need for surgery. Selective cyclooxygenase-2 inhibition appears promising as a therapeutic approach for inflammation, but its suitability for long-term use in the BPH population is limited by safety concerns.
Greater understanding of the relationship between inflammation and the clinical presentation of BPH/LUTS provides an opportunity to effect clinical changes to improve treatment outcomes.
An increased understanding of the role of prostatic inflammation in the pathogenesis, symptomatology, and progression of benign prostatic hyperplasia (BPH) is likely to change the treatment paradigm for BPH.
1 JC Nickel. Prostatic inflammation in benign prostatic hyperplasia - the third component?. Can J Urol. 1994;1:1-4
2 GL Andriole, DG Bostwick, OW Brawley, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192-1202 Crossref
3 JC Nickel, LD True, JN Krieger, RE Berger, AH Boag, ID Young. Consensus development of a histopathological classification system for chronic prostatic inflammation. BJU Int. 2001;87:797-805
4 JC Nickel, CG Roehrborn, MP O'Leary, DG Bostwick, MC Somerville, RS Rittmaster. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol. 2008;54:1379-1384 Crossref
5 G Robert, A Descazeaud, N Nicolaïew, et al. Inflammation in prostatic tissue is associated with symptomatic BPH, IPSS and prostate volume! [abstract 1410]. J Urol. 2009;181(Suppl):504 Crossref
6 G Robert, A Descazeaud, N Nicolaïew, et al. Inflammation in benign prostatic hyperplasia: a 282 patients’ immunohistochemical analysis. Prostate. 2009;69:1774-1780 Crossref
7 JD McConnell, CG Roehrborn, OM Bautista, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387-2398 Crossref
8 C Roehrborn, The MTOPS Research Group. The impact of acute or chronic inflammation in baseline biopsy on the risk of progression in the MTOPS study. Eur Urol Suppl. 2005;4:5
9 A Tuncel, B Uzun, T Eruyar, E Karabulut, S Seckin, A Atan. Do prostatic infarction, prostatic inflammation and prostate morphology play a role in acute urinary retention?. Eur Urol. 2005;48:277-283 discussion 283–4.
10 VC Mishra, DJ Allen, C Nicolaou, et al. Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia?. BJU Int. 2007;100:327-331 Crossref
11 YK Kwon, MS Choe, KW Seo, et al. The effect of intraprostatic chronic inflammation on benign prostatic hyperplasia treatment. Korean J Urol. 2010;51:266-270 Crossref
12 S Moul, KT McVary. Lower urinary tract symptoms, obesity and the metabolic syndrome. Curr Opin Urol. 2010;20:7-12 Crossref
13 D Dallmeier, MG Larson, RS Vasan, et al. Metabolic syndrome and inflammatory biomarkers: a community-based cross-sectional study at the Framingham Heart Study. Diabetol Metab Syndr. 2012;4:28 Crossref
14 M Gacci, L Vignozzi, A Sebastianelli, et al. Metabolic syndrome and lower urinary tract symptoms: the role of inflammation. Prostate Cancer Prostatic Dis. 2013;16:101-106 Crossref
15 KG Alberti, RH Eckel, SM Grundy, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640-1645 Crossref
16 L Vignozzi, M Gacci, I Cellai, et al. Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate. 2013;73:789-800 Crossref
17 C De Nunzio, W Aronson, SJ Freedland, E Giovannucci, JK Parsons. The correlation between metabolic syndrome and prostatic diseases. Eur Urol. 2012;61:560-570 Crossref
18 GP O'Neill, AW Ford-Hutchinson. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993;330:156-160
19 A Kirschenbaum, AP Klausner, R Lee, et al. Expression of cyclooxygenase-1 and cyclooxygenase-2 in the human prostate. Urology. 2000;56:671-676 Crossref
20 F Di Silverio, C Bosman, M Salvatori, et al. Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Eur Urol. 2005;47:72-78 discussion 78–9.
21 I Ozdemir, O Bozkurt, O Demir, G Aslan, AA Esen. Combination therapy with doxazosin and tenoxicam for the management of lower urinary tract symptoms. Urology. 2009;74:431-435 Crossref
22 S Falahatkar, G Mokhtari, F Pourreza, SA Asgari, AN Kamran. Celecoxib for treatment of nocturia caused by benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled study. Urology. 2008;72:813-816 Crossref
23 RS Bresalier, RS Sandler, H Quan, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352:1092-1102 Crossref
24 JC Nickel. Inflammation and benign prostatic hyperplasia. Urol Clin North Am. 2008;35:109-115 Crossref