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The Assessment and Medical Treatment of LUTS Secondary to BPH FEATURE The assessment and medical treatment of LUTS secondary to BPH BY ROGER KIRBY he term benign prostatic are strongly associated with ageing; used invasive urodynamic techniques hyperplasia (BPH) describes associated costs and burden are therefore employed are filling cystometry and prostate enlargement due to likely to increase with future predicted pressure flow studies (PFS). The major Tnon-cancerous processes. Several demographic changes goal of urodynamics is to explore the aetiological mechanisms are involved, functional mechanisms of LUTS and to including hormonal and vascular Assessment of LUTS identify risk factors for adverse surgical alterations; abnormal regulation of Few clinicians would disagree that a full outcomes. PFS are the basis for the apoptosis; and prostatic inflammation, history, International Prostate Symptom definition of bladder outflow obstruction which may stimulate cellular Score (IPSS) and physical examination, (BOO), which is defined as increased proliferation. With ageing, prostate including a digital rectal examination detrusor pressure and decreased urinary enlargement can affect the storage (DRE), are indicated in the assessment flow rate during voiding. BOO has to be and flow of urine, leading to voiding of LUTS, as well as a uroflowmetry and differentiated from detrusor underactivity symptoms (weak flow, intermittency) and measurement of post void residual (DUA), which signifies decreased detrusor storage symptoms (daytime frequency, (PVR). More controversial is the need pressure during voiding in combination nocturia, urgency) in many men. Lower for a prostate specific antigen (PSA) with decreased urinary flow rate [1]. urinary tract symptoms (LUTS) and determination and urodynamic testing. Urodynamic testing may also identify benign prostate obstruction (BPO) occur detrusor overactivity (DO). Studies have secondary to BPH due either to increased PSA described an association between BOO smooth muscle tone within the prostate, Quite apart from its ability to predict and DO. In men with LUTS attributed to BPE, DO was present in 61% and or to the bulky enlargement of the the presence of prostate cancer, pooled independently associated with BOO grade prostate. Approximately 90% of men will analysis of placebo-controlled BPH and ageing. The prevalence of DUA in men develop histologic evidence of BPH by the trials showed that PSA has a good with LUTS varies from 11-40%. Detrusor age of 80 years. predictive value for assessing prostate contractility does not appear to decline in LUTS can be divided into storage, volume, with areas under the curve long-term BOO and surgical relief of BOO voiding and post-micturition symptoms. (AUC) of 0.76-0.78 for various prostate volume thresholds (30ml, 40ml, and does not always improve contractility. LUTS are prevalent, cause bother and 50ml). A strong association between Due to the invasive nature of the test, a impair quality of life (QoL). Increasing PSA and prostate volume was found in urodynamic investigation is generally only awareness of LUTS and storage a large community-based study. A PSA recommended if conservative treatment symptoms in particular, should lead threshold value of 1.5ng/ml could best has failed. to a discussion about management predict a prostate volume of >30ml, with options that could improve QoL. LUTS a positive predictive value (PPV) of 78%. Non-invasive treatment options Serum PSA is a stronger predictor of prostate growth than prostate volume. Watchful waiting “Men with LUTS In addition, the PLESS study showed Many men with LUTS are not sufficiently that PSA also predicted the changes in troubled by their symptoms to require should be formally symptoms, QoL / bother, and maximum drug treatment or surgical intervention. assessed prior to any flow rate (Qmax). In a longitudinal study Men with LUTS should be formally of men managed conservatively, PSA was assessed prior to any allocation of allocation of treatment a highly significant predictor of clinical treatment in order to establish symptom progression. In the placebo arms of large severity and to differentiate between in order to establish double-blind studies, baseline serum men with uncomplicated (the majority) symptom severity PSA predicted the risk of acute urinary and complicated LUTS. Watchful waiting retention (AUR) and BPE-related surgery. (WW) is a viable option for many men and to differentiate An equivalent link was also confirmed with non-bothersome LUTS as few will by the Olmsted County Study. The risk progress to AUR or other complications between men with for treatment was higher in men with a (e.g. renal insufficiency or stones), while uncomplicated baseline PSA of >1.4ng/m. Patients with others can remain stable for many BPO in general seem to have a higher PSA years. One study comparing WW and (the majority) and level and larger prostate volumes. transurethral resection of the prostate complicated LUTS.” (TURP) in men with moderate LUTS Urodynamics showed the surgical group had improved In male LUTS, the most commonly bladder function (flow rates and PVR urology news | NOVEMBER/DECEMBER 2016 | VOL 21 NO 1 | www.urologynews.uk.com FEATURE Figure 1: Axial MRI scan demonstrating BPH. Figure 2: Ultrasound axial and longitudinal image with the gland size being measured. volumes), especially in those with high age groups. α1-blockers neither reduce dutasteride reduces IPSS, prostate volume, levels of bother; 36% of WW patients prostate size nor prevent AUR in long-term and the risk of AUR, and increases Qmax crossed over to surgery within five years, studies; some patients must therefore even in patients with prostate volumes of leaving 64% doing well in the WW group be treated surgically. Nevertheless, IPSS between 30 and 40ml at baseline. A long- [2]. Increasing symptom bother and PVR reduction and Qmax improvement during term trial with dutasteride in symptomatic volumes are the strongest predictors of α1-blocker treatment appears to be men with prostate volumes >30ml and clinical failure. Men with mild-to-moderate maintained over at least four years. increased risk for disease progression uncomplicated LUTS who are not too 5α-reductase inhibitors showed that dutasteride reduced LUTS at troubled by their symptoms may be Two 5α-reductase inhibitors (5-ARIs) least as much as, or even more effectively considered suitable for WW. are currently available for clinical use: than, the α1-blocker tamsulosin. The dutasteride and finasteride. Finasteride greater the baseline prostate volume (or Pharmacological management inhibits only 5α-reductase type 2, whereas serum PSA concentration), the faster and α1-adrenoceptor antagonists (α1-blockers) dutasteride inhibits 5α-reductase types more pronounced the symptomatic benefit aim to inhibit the effect of noradrenaline 1 and 2 with similar potency (dual 5-ARI). of dutasteride as compared to tamsulosin. on smooth muscle cells in the prostate Five-ARIs act by inducing apoptosis of Five-ARIs, but not α1-blockers, reduce the and thereby reduce prostate tone and prostate epithelial cells leading to prostate long-term (greater than one year) risk of BOO. However, α1-blockers have little size reduction of about 18-28% and a AUR or need for surgery. In the Proscar effect on urodynamically determined decrease in circulating PSA levels of about Long-Term Efficacy and Safety Study, bladder outlet resistance, and treatment- 50% after 6-12 months of treatment. finasteride treatment reduced the relative associated improvement of LUTS is Mean prostate volume reduction and PSA risk of AUR by 57%, and surgery by 55% at correlated only poorly with obstruction. decrease may be even more pronounced four years, compared with placebo [5]. In Currently available α1-blockers include: after long-term treatment. Continuous the MTOPS study, a significant reduction alfuzosin hydrochloride (alfuzosin); treatment reduces the serum DHT in the risk of AUR and surgery in the doxazosin mesylate (doxazosin); silodosin; concentration by approximately 70% with finasteride arm compared with placebo tamsulosin hydrochloride (tamsulosin); finasteride and 95% with dutasteride. was reported (68% and 64%, respectively) terazosin hydrochloride (terazosin). However, prostate DHT concentration is [6]. Indirect comparisons and limited direct reduced to a similar level (85-90%) by both A pooled analysis of randomised trials comparisons between α1-blockers 5-ARIs. with two-year follow-up data reported that demonstrate that all α1-blockers have Clinical effects relative to placebo are treatment with finasteride significantly a similar efficacy in appropriate doses seen after a minimum treatment duration decreased the occurrence of AUR by [3]. Beneficial effects take a few weeks of at least 6-12 months. After two to four 57%, and surgical intervention by 34%, to develop fully, but significant efficacy years of treatment, 5-ARIs improve IPSS by in moderately symptomatic LUTS [7]. over placebo can occur within a few approximately 15-30%, decrease prostate Dutasteride has also demonstrated efficacy days. Placebo controlled studies show volume by 18-28%, and increase Qmax by in reducing the risks for AUR and BPH- that α1-blockers typically reduce IPSS by 1.5-2.0ml/s in patients with LUTS due to related surgery. approximately 30-40% and increase Qmax prostate enlargement. Indirect comparison by approximately 20-25%. α1-blockers can and one 12-month comparative trial Antimuscarinic agents reduce both storage and voiding LUTS. indicate that dutasteride and finasteride
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