1 Dunsmuir WD, Feneley M, Corry DA, et al. (1996) The day-to-day variation (test \200\223re test reli- ability) of residual urine measurement. Br J Urol 77:192 \200\2233. 2 Denis L, Grif \201 ths K, Khoury S, et al. (eds) (1998) Fourth International Consultatio n on Benign Prostatic Hyperplasia (BPH), Paris, July 1997. Plymouth: Health Publications. 3 Bates TS, Sugiono M, James ED, et al. (2003) Is the conservative management of chronic re ten- tion in men ever justi \201 ed? Br J Urol Int 92:581 \200\2233. 4 Riehmann M, Goetzmann B, Langer E, et al. (1994) Risk factor for bacteriuria in men. Urol ogy 43:617 \200\22320. 5 Hampson SJ, Noble JG, Rickards D, Milroy EG (1992) Does residual urine predispose to urin ary tract infection. Br J Urol 70:506 \200\2238. 6 Crawford ED, Wilson SS, McConnell JD, et al. (2006) Baseline factors as predictors of cli nical progres- sion of benign prostatic hyperplasia in men treated with placebo. J Urol 175 :1422. 7 Mochtar CA, Kiemeney LA, van Riemsdijk MM, et al. (2006) Post-void residual urine volume is not a good predictor of the need for invasive therapy among patients with benign prostat ic hyperplasia. J Urol 175:213 \200\2236. 8 Thomas AW, Cannon A, Bartlett E, Ellis-Jones J, Abrams P (2005) The natural history of lo wer urinary tract dysfunction in men: minimum 10-year urodynamic follow-up of untreated bla dder outlet obstruction. BJU Int 96:1301 \200\2236. CHAPTER 3 Urological investigations 68 Cystometry, pressure \202 ow studies, and videocystometry - Cystometry: the recording of bladder pressure during bladder \201 lling. - Pressure \200\223 \202 ow studies (PFS): t he simultanous recording of bladder pressure during voiding. Videocystometry: \202 uoroscopy (X-ray screening) combined with PFS during voiding (see b p. 57; Fig. 3.8). These techniques provide the most precise measurements of bladder and urethral sphincter be havior during bladder \201 lling and during void- ing. Cystometry precedes the pressure \200\223 \202 ow study. Bladder pressure (Pves, measured by a urethral or suprapubic cathe ter) and abdominal pressure (Pabd, measured by a pressure line inserted into the rectum) ar e recorded as the bladder \201 lls (cystometric phase) and empties (void- ing phase) and \202 ow rate is simultaneously measured during the voiding phase. The pressure developed by the detrusor (the bladder muscle), Pdet, cannot be directly measured, but it can be deri ved by subtracting abdominal pressure from the pressure measured within the bladder (the in travesical pressure). This allows the effect of rises in intra- abdominal pressure caused b y coughing or straining to be subtracted from the total (intravesical) pressure so that a \200\230pure \200\231 detrusor pressure is obtained. All pressures are recorded in cmH2O and \202 ow rate is measured in mL/s. The pressure li nes are small-bore, \202 uid- \201 lled catheters attached to an external pressure trans ducer or catheter-tip pressure transducers can be used. A computerized printout of Pves, Pabd and Pdet, and \202 ow rate (Qmax) is obtained (Fig. 3.15). During bladder \201 lling, the presence of overactive bladder contractions can be detected. During voiding, the key parame- ters are Qmax and the detrusor pressure at the p oint at which Qmax is reached, Pdet Qmax. This pressure, relative to Qmax, can be used to d e \201 ne the presence of BOO by using a variety of nomograms, of which the ICS nomogram i s most widely used. CYSTOMETRY, PRESSURE FLOW STUDIES, VIDEOCYSTOMETRY 69 Fill & void cys to + video (spinal)#1 120 100 80 60 40 20 0 40 20 0 40 20 0 2 1 0 1000 500 0 Pabd cm H2O Pves cm H2O Pdet cm H2O Qura ml/s EMG V 30s 00:00 01:00 02:00 03:00 04:00 Fig. 3.15 A computerized printout of intravesical pressure (Pves), intra-abdominal pressure (Pabd), subtracted detrusor pressure (Pdet), and \202 ow rate (Qmax). This page intentionally left blank 71 Chapter 4 Bladder outlet obstruction Regulation of prostate growth and development of benign prostatic hyperplasia (BPH) 72 Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH 73 Benign prostatic obstruction (BPO): symptoms and signs 74 Diagnostic tests in men with LUTS thought to be due to BPH 76 The management of LUTS in men: NICE 2010 Guidelines 78 Watchful waiting for uncomplicated B PH 84 Medical management of BPH: alpha blockers 86 Medical management of BPH: 5 -reductase inhibitors 88 Medical management of BPH: combination therapy 90 Medical management of BPH: alternative drug therapy 92 Minimally invasive management of BPH: surgical alternatives to TURP 94 Invasive surgical alternatives to TURP 96 TURP and open prostatectomy 100 Acute urinary ret ention: de \201 nition, pathophysiology, and causes 102 Acute urinary retention: initial and de \201 nitive management 106 Indications for and tec hnique of urethral catheterization 108 Technique of suprapubic catheterization 110 Manageme nt of nocturia and nocturnal polyuria 116 Chronic retention 118 High-pressure chronic reten tion (HPCR) 120 Bladder outlet obstruction and retention in women 122 Urethral strictures a nd stenoses 124 CHAPTER 4 Bladder outlet obstruction 72 Regulation of prostate growth and development of benign prostatic hyperplasia (BPH) BPH is characterized by an increase in epithelial and stromal cell numbers (hyperplasia) in the pe ri-urethral area of the prostate. New epithelial gland formation is normally only seen duri ng fetal development. The develop- ment of new glands in the adult prostate has given rise to the concept of \200\230reawakening \200\231 of the inductive effect of the prostatic st roma on the prostatic epithelium. The increase in prostate cell number could re \202 ect proliferation of epithelial and str omal cells, impairment of programmed cell death, or a combination of both. During the early phases of development of BPH, cell proliferation occurs rapidly. In established BPH, cell proliferation slows down and there is impairment of programmed cell death (androgens and oe strogens actively inhibit cell death). The role of androgens in BPH Testosterone can bind directly to the androgen receptor or may be con- verted to a more potent form, dihydrotestosterone (DHT), by the enzyme 5 -reducta se (5AR). There are two isoforms of 5AR, type I or \200\230extraprostatic \200\231 5AR (wh ich is absent in prostatic tissue and present in, for example, skin and liver) and type II or \200\230prostatic \200\231 5AR (which is found exclusively on the nuclear membrane of s tromal cells, but not within prostatic epithelial cells). Type I 5AR is not inhibited by \201 nasteride whereas type II 5AR is. Dutasteride inhibits both types I and II 5AR. Finast eride reduces serum DHT by about 70% and dutasteride by about 95%. Finasteride reduces pros tatic DHT (type II) by about 80% and dutasteride by about 94%. We do not know whether these differences translate into differences in clinical ef \201 cacy since neither drugs has b een compared against the other. Testosterone diffuses into prostate and stromal epithelial cells. Within epithelial cells, it binds directly to the androgen receptor. In prostate stromal cells, a small proportion b inds directly to the androgen receptor, but the majority binds to 5AR (type II) on the nucl ear membrane, is con- verted to DHT, and then binds (with greater af \201 nity and, theref ore, greater potency than testosterone) to the androgen receptor in the stromal cell. Some of the DHT formed in the stromal cells diffuses out of these cells and into nearby epitheli al cells (a paracrine action). The androgen receptor/ testosterone or androgen receptor/DHT complex then binds to speci \201 c binding sites in the nucleus, thereby inducing transcr iption of androgen- dependent genes and subsequent protein synthesis. It is thought that stromal/epithelial interactions may be mediated by soluble growth factor s \200\224small peptides that stimulate or inhibit cell divi- sion and differentiation. Gro wth stimulating factors include basic \201 brob- lastic growth factor (bFGF), epidermal g rowth factor (EGF), keratinocyte growth factor (KGF), and insulin-like growth factor (IGF). Transforming growth factors (e.g. TGFB) normally inhibit epithelial cell proliferation and it is possible that in BPH, TGFB is downregulated. PATHOPHYSIOLOGY AND CAUSES OF BOO AND BPH 73 Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH The principal cause of BOO in men is BPH. Less common causes are ure- thral stricture and malignant enlargement of the prostate. BOO in women is altogether less common, the causes including pelvic prola pse (cystocele, rectocele, uterine), the prolapsing organ directly compressing the urethra; urethral stricture; urethral diverticulum; post-surgery for \200\230stress \200\231 incon - tinence; Fowler \200\231s syndrome (impaired relaxation of external sphincter occurring i n premenopausal women, often in association with polycystic ovaries); and pelvic masses (e. g. ovarian masses). In either sex, neuro- logical disease (spinal cord injury, spina bi \201 da, multiple sclerosis (MS)) can cause failure of relaxation of the external sphincter during voiding (detru- sor sphincter dysynergia, DSD). The pathophysiological basis of BOO due to benign prostatic enlarge- ment (BPE) secondary t o BPH (benign prostatic obstruction, BPO) has been studied more than any other type of obst ruction. BPO has dynamic and static components: \200 Dynamic component of BPO: smooth muscle contraction. Smooth muscle accounts for approximate ly 40% of the area density of the hyperplastic prostate and human prostate contracts follow ing administration of alpha adrenergic agonists. This effect is the rationale for -adreno ceptor blocker treatment for symptomatic BPO. Static component of BPO: 1-adrenoceptor-mediated prostatic mediated by the volume effect of BPE. Pathophysiological consequences of BOO John Hunter (1786), who founded the Royal College of Surgeons of England, noted that \200\230The disease of the bladder arising from obstructi on alone is increased irritability and its consequences, by which it admits of little diste nsion, becomes quick in its action, and thick and strong in its coats \200\231. BOO causes thickening of the wall of the bladder. Microscopically, smooth muscle cells enlarge and the re is an increase in connective tis- sue (collagen and elastin) between the smooth muscle b undles. In some cases, this may lead to poor compliance, with development of high bladder a nd intrarenal pressures. Progressive hydronephrosis can develop, with impairment of renal f unction and even renal failure (high-pressure chronic urinary retention). Experimentally created BOO causes development of bladder overac- tivity (unstable bladder c ontractions during bladder \201 lling). This may be due to prolonged increased intravesic al pressure during voiding, causing ischaemia and leading to ischaemic damage to neurons wi thin the blad- der (i.e. denervation). Symptomatically, many patients with BOO develop freq uency, urgency, and urge incontinence. CHAPTER 4 Bladder outlet obstruction 74 Benign prostatic obstruction (BPO): symptoms and signs Clinical practice guidelines Develop ed to standardize the approach to diagnosis (and treatment) of men presenting with symptoms suggestive of BPH.1 Every guideline agrees that a history should be taken, an examination performed, and that the severity of urinary symptoms should be formally assessed using the IPSS. This includes a measure of the \200\230bother \200\231 caused by the patient \200 \231s symptoms (i.e. the degree to which the symptoms are troubling). Urinary symptoms \200\224what do they mean? During the 1990s, the classic \200\230prostati c \200\231 symptoms of frequency, urgency, nocturia, hesitancy, poor \202 ow, intermitten t \202 ow, and terminal dribbling \200\224 traditionally said to indicate the presence of BOO due to BPE \200\224were shown to bear little relationship to prostate size, \202 ow rate, residual urine volume, or indeed, urodynamic evidence of BOO. Age-matched elderly men and women have similar symptom scores (IPSS), despite the fact that women have no prostate and rarely have BOO. Prostatism vs LUTS vs LUTS/BPH \200\230Prostatism \200\231 has, therefore, been replaced b y the expression \200\230LUTS \200\231, which avoids any implication about the cause of th ese symptoms. More recently, the expression \200\230LUTS/BPH \200\231 has been used to des cribe the symptoms of BPH. It doesn \200\231t really matter whether you use \200\230prosta tism \200\231, \200\230LUTS \200\231, or \200\230LUTS/BPH \200\231, as long as you rememb er that urinary symptoms may have non-prostatic causes. Try to avoid treating the prostate when the problem may lie elsewhere. Ask speci \201 cally about the presence of: Bedwetting: suggests the presence of high-pres sure chronic retention (look for distension of the abdomen due to a grossly enlarged bladde r that is tense on palpation and dull to percussion). Marked frequency and urgency, particu larly when also combined with bladder pain: look for carcinoma in situ of the bladder (urin e cytology, \202 exible cystoscopy, and bladder biopsy). Macroscopic haematuria: but excl ude other causes (bladder and kidney cancer and stones) by \202 exible cystoscopy and upp er tract imaging. Back pain and neurological symptoms or tingling): rarely, LUTS can be due to neurological disease. sometimes due to a large vascular prostate, (sciatica, lower limb weakness, 1 Irani J, Brown CT, van der Meulen J, Emberton M (2003) A review of guidelines on benign p rostatic hyperplasia and lower urinary tract symptoms: are all guidelines the same? BJU Int 92:937 \200\22342. BENIGN PROSTATIC OBSTRUCTION (BPO): SYMPTOMS AND SIGNS 75 Websites for BPH clinical practice guidelines \200 \200 \200 M http://hstat.nlm.NIH.gov/ftrs/arahcpr. M http://www.uroweb.org/ \201 les/uploaded_ \201 les/BPH.pdf. AUA guidelines. EAU guidelines. WHO (International Consensus Committee) guidelines. www.who .int/ina-ngo/ngo/ngo048.htm. Australian guidelines. publications/pdf/cp42.pdf. German guide lines. Singapore guidelines. guidelines_BPH.htm. Malaysian guidelines. BPH98.pdf. UK guidel ines. M http:// M http://www.health.gov.au/nhmrc/ \200 M http://dgu.springer.de/Leit/pdf/3_99.pdf. M http://www.urology-singapore.org.html/ M http://www.mohtrg.gov.my/guidelines/ M http://www.rcseng.ac.uk/publications/. CHAPTER 4 Bladder outlet obstruction 76 Diagnostic tests in men with LUTS thought to be due to BPH Clinical practice guidelines Dev eloped as an attempt to standardize the approach to diagnosis and treatment of men presenti ng with symptoms suggestive of BPH.1 All agree that a history should be taken, an examinati on performed, and all rec- ommend assessment of symptom severity using the IPSS. This inclu des a measure of the \200\230bother \200\231 caused by the patient \200\231s symptoms. The re is considerable variation between guidelines in terms of recommended diag- nostic tests. High-quality guidelines (e.g. based on results of randomized trials) recommend few diagnos tic tests2 \200\224urine analysis, completion of a voiding diary (frequency \200\223volume chart) to detect the presence of polyuria and nocturnal polyuria (which may be the cause of a patient \200\231s increased frequency or nocturia), and measurement of serum creatinine. They regard \202 ow rate measurement and assessment of residual urine volume as optional tests. DRE and PSA Done to detect nodules that may indicate an underlying prostate cancer and to p rovide a rough indication of prostate size. Size alone is not an indication for treatment, but if surgical treatment is contemplated, marked prostatic enlargement can be con \201 rm ed by transrectal ultrasound scan (prostate volume in the order of 100mL or more increases the likelihood of an open prostatectomy). Discuss the pros and cons of PSA testing with the patient. Serum creatinine Baseline measure of renal function and to detect renal failure secondary t o high-pressure urinary retention. Post-void residual urine volume (PVR) Varies considerably (by as much as 600mL between repe at measurements) on the same or different days.3 It cannot predict symptomatic outcome from TURP. Along with serum creatinine, it indicates whether watchful waiting is safe. It is sa fe not to operate where the PVR volume is <350mL,4,5 since the majority of men show no wors ening of creatinine, no increase in PVR, no worsening of symptoms, and do not require TURP. Flow rate measurement This is variously regarded as optional, recommended, and obligatory p rior to undertaking surgical treatment for BPH. Like PVR, measurement of \202 ow rate var ies substantially on a given day,6 cannot distinguish between BOO and a poorly contractile bladder, and is not good at predicting the likeli- hood of a good symptomatic outcome after TURP. DIAGNOSTIC TESTS IN MEN WITH LUTS 77 Pressure \202 ow studies Reasonably good at predicting symptomatic outcome after TURP. Ho wever, most patients without obstruction have a good outcome and the time, cost, and invasi veness of pressure \202 ow studies is perceived by most urologists as not justifying thei r routine use. The AUA Guidelines on the management of BPH (M http://www.auanet.org) regard s pressure \202 ow studies as optional since they are unable to reliably predict treatmen t failure in the individual patient (treatment failure is somewhat higher in the absence of obstruction, but unobstructed individuals still have a reason- able chance of improvement with TURP). The AUA Guidelines speci \201 cally state that \200\230If interventional ther apy is planned without clear evidence of the presence of obstruction, the patient needs to be informed of possible higher failure rates of the procedure \200\231. Renal ultrasonography To detect hydronephrosis if serum creatinine is elevated. The percent age of patients having upper tract dilatation on ultrasound according to serum creatinine i s: creatinine <115mmol/L: 0.8%; creatinine 115 \200\223130mmol/L: 9%; and creatinine >130mm ol/L: 33%.7 1 Roehrborn CG, Bartsch G, Kirby R, et al. (2001) Guidelines for the diagnosis and treatmen t of benign prostatic hyperplasia: a comparative international overview. Urology 58:642 \200\22350. 2 plasia and lower urinary tract symptoms: are all guidelines the same? Br J Urol Int 92:93 7 \200\22342. Irani J, Brown CT, van der Meulen J, Emberton M (2003) A review of guidelines on benign pro static hyper- 3 Dunsmuir WD, Feneley M, Corry DA, et al. (1996) The day-to-day variation (test \200\223re test reliability) of residual urine measurement. Br J Urol 77:192 \200\2233. 4 Bates TS, Sugiono M, James ED, et al. (2003) Is the conservative management of chronic re tention in men ever justi \201 ed? Br J Urol Int 92:581 \200\2233. 5 Wasson JH, Reda DJ, Bruskewitz RC, et al. (1995) A comparison of transurethral surgery wi th watchful waiting for moderate symptom of benign prostatic hyperplasia. The Veterans Admi nistration Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med 332:75 \200\2239. 6 Reynard JM, Peters TJ, Lim C, Abrams P (1996) The value of multiple free- \202 ow studie s in men with lower urinary tract symptoms. Br J Urol 77:813 \200\22318. 7 Koch WF, Ezz el Din KE, De Wildt MJ, et al. (1996) The outcome of renal ultrasound in the assessment of 556 consecutive patients with benign prostatic hyperplasia. J Urol 155:186 \200\2239. CHAPTER 4 Bladder outlet obstruction 78 The management of LUTS in men: NICE 2010 Guidelines (M www.nice.org.uk/CG97) For those prac ticing in the UK, the NICE 2010 LUTS Guidelines provide a helpful summary of diagnostic and treatment options for men with LUTS. Like guidelines in general, they are not written in s tone \200\224there is no abso- lute requirement to follow them to the letter; you may \200 \230step outside \200\231 the guidelines as long as your rationale for doing so has a logic al (reasonable) basis. Differences exist between those aspects of the NICE Guidelines that cover BPH-related LUTS and the AUA 2010 Guidelines on the manage- ment of BPH (M http://www .auanet.org) and these differences are high- lighted where relevant. LUTS are classi \201 ed according to IPSS as mild 0 \200\2237, moderate 8 \200\22319, and severe 20 \200\22335. Initial assessment (i.e. primary care) Assess general medical history to identify possible causes of LUTS and comorbidities; examine abdomen, genitals, DRE; dipstick urine for blood, glucose, protein, leucocytes, nitrites; complete FVC; serum creatinine and eGFR only if su spected renal impairment. Offer information, advice, and time to decide if they wish to have PSA testing if LUTS are suggestive of BOO secondary to BPE or abnormal feel- ing of prostate on DRE or patient conc erned about prostate cancer. Do not routinely offer cystoscopy, \202 ow rate, or residual urine volume measurement. Offer lifestyle advice (e.g. advice on \202 uid intake); mild or moderate both- ersome LU TS \200\224discuss active surveillance* (reassurance, lifestyle advice, no immediate treatm ent, regular follow-up) or active intervention (con- servative management, drugs, surgery). Conservative management \200 Storage symptoms: supervised bladder training, advice on \202 uid intake, lifestyle advice and, if needed, containment products, i.e. pads or sheath s; offer supervised pelvic \202 oor exercises for stress incontinence caused by \200\224c ontinue for at least 3 months before considering other options. Voiding symptoms: indwellin g or suprapubic catheterization if less invasive means fail to correct LUTS; tell men with proven BOO that bladder training is less effective than surgery; for post-micturition dribb ling, explain how to do urethral milking. If overactive bladder (OAB) suspected, offer offer intermittent self-catheterization (ISC) before AUA 2010 Guidelines use the terms \200\230watchful waiting \200\231 and \200\230active su rveillance \200\231 interchangeably; it de \201 nes \200\230watchful waiting \200\231 as \200\230a management strategy in which the patient is monitored by his physician, but curr ently receives no active intervention \200\231. Watchful waiting is recommended for patient s with mild symptoms (AUA-SI <8) and patients with AUA-SI of 8 or more who are not bothered by their LUTS. THE MANAGEMENT OF LUTS IN MEN: NICE 2010 GUIDELINES 79 Drug treatment \200 Offer drug treatment where conservative options are unsuccessful or inappropriate; take acc ount of comorbidities and current treatments; do not offer homeopathy, phytotherapy, or acu puncture (Table 4.1). Table 4.1 Drug treatment Indication Treatment Review At 4 \200\2236wk (AUA Guidelines 2 \200\2234wk), then every 6 \200\22312mo Moderate to severe LUTS Offer an alpha blocker (alfuzosin, doxazosin, tamsulosin, terazosin) OAB Offer an anticholinergic At 4 \200\2236wk until stable, then every 6 \200\22312mo LUTS, prostate estimated >30g or PSA >1.4ng/ mL and high risk of progression Offer 5A-reductase inhibitor At 3 \200\2236mo, then every 6 \200\22312mo Bothersome moderate to severe LUTS and prostate estimated >30g or PSA >1.4ng/mL Consider an alpha blocker plus 5A-reductase inhibitor At 4 \200\2236wk, then every 6 \200\22312mo for the alpha blocker; at 3 \200\2236mo, then e very 6 \200\22312mo for the 5A-reductase inhibitor Storage LUTS despite alpha blocker treatment alone Consider adding an anticholinergic At 4 \200\2236wk until stable, then every 6 \200\22312mo Nocturnal polyuria: and insipidus, adrenal insuf \201 ciency; hypercalcaemia; liver failur e; polyuric renal failure; chronic heart failure; obstructive sleep apnoea, dependent oedem a; chronic venous stasis; calcium channel blockers; diuretics; selective serotonin reuptake inhibitor antidepressants. Consider a late afternoon loop diuretic. Consider offering oral desmopressin \200\224measure serum sodium 3 days after \201 rst dose; stop if sodium fal ls below normal reference range. exclude other medical causes \200\224diabetes mellitus Refer for specialist assessment If bothersome LUTS that fails to respond to conservative ma nagement or drugs; LUTS complicated by recurrent or persistent urinary tract infec- tion (U TI); retention; renal impairment suspected to be caused by LUT dysfunction; suspected urolo gical cancer; stress incontinence. CHAPTER 4 Bladder outlet obstruction 80 Specialist assessment (i.e. secondary care \200\224 \200\230health care professional with s peci \201 c training in managing LUTS in men \200\231) . A summary of surgical treatment o ptions, based on prostatic size, for voiding symptoms is shown in Table 4.2 and for stor- a ge symptoms in Table 4.3. Table 4.2 Voiding symptoms Prostate size Type of surgery All TURP (monopolar or bipolar); TUVP (monopolar); HoLEP* Estimated <30g TUIP (BNI) as an alternative to the above Estimated >30g TURP, TUVP, HoLEP*, open prostatectomy At a center specializing in the technique or with mentorship arrangement in place, holmium laser enucleation of the prostate. Offer the following only as part of a randomized controlled trial (RCT): prostatic botox in jection; laser vaporization techniques; bipolar TUVP; TUVRP (monopolar or bipolar transuret hral vaporization resection of the prostate). Do not offer any of the following as an alter native to TURP, TUVP, or HoLEP: \200 Transurethral needle ablation of the prostate (TUNA); transurethral microwave thermotherapy of the prostate (TUMT); high intensity focused ultrasound (HIFU); laser coagulation; trans urethral ethanol ablation of the prostate (TEAP) (AUA 2010 Guidelines include TUNA and TUMT as treatment options for the patient with moderate to severe LUTS, i.e. IPSS 8 or more). Table 4.3 Storage symptoms Indication Type of surgery Detrusor overactivity Consider offering bladder wall botox injection (must be willing and able to do ISC); SNS*; cystoplasty (must be willing and able to do ISC) Stress incontinence Consider AUS (intramural injectables, implanted adjustable compression devices, male slings \200\224only as part of an RCT) Intractable LUTS if cystoplasty or SNS not clinically appropriate or unacceptable to patien t Consider offering urinary diversion SNS = sacral nerve stimulation (the Interstim). THE MANAGEMENT OF LUTS IN MEN: NICE 2010 GUIDELINES 81 Why do men seek treatment for their symptoms? Men seek treatment for their LUTS for several reasons: \200 \200 The symptoms may be bothersome. They may fear that the symptoms are a warning that acute ur inary retention will develop. They may be concerned that their symptoms indicate that they have prostate cancer. Establish what the patient wants from his consultation with you. Once reassured that the li kelihood of urinary retention and prostate cancer is low, he may not want treatment for sym ptoms that, on the surface, may appear quite bad and he may be happy to adopt a policy of w atchful waiting. Goals of treatment \200 \200 \200 To improve bothersome symptoms. To prevent symptom progression. To reduce long-term complic ations (urinary retention, renal insuf \201 ciency). Management options include watchful w aiting, lifestyle modi \201 cation, drug treatments ( -adrenergic blockers, 5 -reductase inhibitors, anticholinergics, plant extracts), minimally invasive surgery, TURP, open pros tatectomy. The choice of treatment is determined by the patient based on his perception of how bad (bothersome) his symptoms are, balanced against the perceived bene \201 t and risk s of the various options. Drug treatments have the least impact on symptoms, but are genera lly safe. Minimally invasive surgery has a somewhat greater impact, with a higher risk of s ide effects. TURP and open prostatectomy have the greatest impact on symptoms, but at the r isk of potentially serious complications. Bothersome symptoms Bothersomeness does not necessarily equate with symptom severity as ass essed by symptom scores. Thus, a man with a low symptom score may \201 nd his symptoms ve ry bothersome and may want treatment, whereas another man with a high symptom score may not be bothered and may want no treatment. If one symptom is particularly bad, but the other s ix symptoms in the 7-symptom score are minimal, overall symptom score will obviously be rel atively low, but the patient may \201 nd that one symptom very bothersome (e.g. urgency a nd nocturia tend to be more bothersome than hesitancy or poor \202 ow). \200\230Are my symptoms due to prostate cancer? \200\231 No particular LUTS are speci \201 c for prostate cancer. Even if it later turns out that he does have prostate cancer, a patient \200\231s symptoms might be due to coexistent BPH or some other LUT pathology. If he is concerned about the possibility of prostate cancer, counsel him with regard to PSA te sting and prostate biopsy. \200\230Am I likely to develop retention of urine? \200\231 Many patients are understandab ly concerned that their urinary symp- toms may be a harbinger for the development of acute urinary retention. CHAPTER 4 Bladder outlet obstruction 82 This may in \202 uence their decision to seek help for symptoms, which they may perceive a s indicating a risk of subsequent retention and it may affect the type of treatment they ch oose. Table 4.4 can help give the patient some idea of his risk of developing urinary reten tion. Table 4.4 Yearly risk of retention according to age and symptom score (i.e. number of men e xperiencing an episode of retention every year)* Age (y) Mild symptoms (AUA symptom score 7 or less) Moderate or severe symptoms (AUA symptom score >7) 440 \200\22349 3 3 men in every 1000 33 men in every 1000 770 \200\22379 9 9 men in every 1000 334 men in every 1000 Adjusting for age and \202 ow rate, those with an AUA symptom score of 8 or more had a 2. 3-fold increased risk of going into urinary retention when compared with those with an AUA score of 7 or less. Those men with a peak \202 ow rate of <12mL/s had a 4-fold increased risk of urinary retention when compared with those with a \202 ow rate of >12mL/s. Prosta te volume >30mL was associated with a 3-fold increased risk of urinary retention compared w ith those with prostate volumes <30mL. * This table is taken from Jacobsen \200\231s report , a 4-year prospective study of a cohort of >2000 men.1 The presence of LUTS, a low \202 ow rate, an enlarged prostate, and old age were associated with an increased risk of urinar y retention. 1 acute urinary retention. J Urol 158:481 \200\2237. Jacobsen SJ, Jacobson DJ, Girman CJ, et al. (1997) Natural history of prostatism: risk fact ors for This page intentionally left blank CHAPTER 4 Bladder outlet obstruction 84 Watchful waiting for uncomplicated BPH A number of studies have shown that in a substantial proportion of men, symptoms do not progress, even for those with severe symptoms. \200 1 a total of 107 men followed with watchful waiting over 5y. In Ball: none was there an abs olute indication for surgery. Half of the patients were obstructed on urodynamic testing. A third of the patients got better, just under a half stayed the same, a fourth got worse (o f whom eight underwent TURP); 2% went into retention. PLESS study (Proscar long-term ef \201 cacy and safety study): of 1500 men with moderate to severe symptoms were randomized t o placebo (and a similar number to active drug). Those on placebo had an average fall in sy mptom score of 1 point at 4y. Wasson study of watchful waiting versus TURP: moderate sympto ms, the risk of progression to retention, worsening symptoms, or need for TURP was relative ly low in those who chose watchful waiting; 40% noticed an improvement in their symptoms, 3 0% got worse, and TURP was required in about a fourth. Five centers \200\231 study: doctors for consideration for TURP were managed non-operatively after viewing an educational progr am. Over the following 4y period, a proportion of the men chose drug treatment or surgery. For men with mild, moderate, or severe symptoms, 10%, 24%, and 39%, respectively, had under gone surgery at the end of 4y. For the same symptom categories, 63%, 45%, and 33% were stil l not receiving any treatment at the end of 4y. Almost a fourth of men who initially presen ted with severe symptoms noted an improvement in their symptoms to mild or moderate. 2 a total 3 for men with 4 a total of 500 men referred by their family On the basis of these studies, we can say that symptoms, even if severe, do not necessarily get worse, even over fairly long periods of time. This forms the foundation of watchful wa iting as an option for many patients, even if the symptoms at baseline are severe. The IPSS measures both symptom \200\230severity \200\231, but more importantly, the bother that th e symptoms cause the patient. Thus, if a patient has a high symptom score (severe symptoms) , but is not bothered by these symptoms, there is no indication for treatment. Some patient s, on the other hand, have a low symptom score, but may \201 nd even this degree of symp- toms very bothersome. Treatment is indicated in such cases (usually starting with medical therapy such as an alpha blocker or 5 -reductase inhibitor). 1 Ball AJ, Feneley RC, Abrams PH (1981) Natural history of untreated \200\230prostatism \200\231. Br J Urol 53:613 \200\22316. 2 McConnell JD, Bruskewitz R, Walsh PC, et al. (1998) The effect of \201 nasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia (PLESS). N Engl J Med 338:557 \200\22363. 3 Wasson JH, Reda DJ, Bruskewitz RC, et al. (1995) A comparison of transurethral surgery wi th watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Aff airs Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med 332:7 5 \200\2239. 4 Barry MJ, Fowler FJJ, Bin L, et al. (1997) The natural history of patients with benign pr ostatic hyperplasia as diagnosed by North American urologists. J Urol 157:10 \200\2234. This page intentionally left blank CHAPTER 4 Bladder outlet obstruction 86 Medical management of BPH: alpha blockers The rationale for blocker therapy in BPH As descr ibed earlier, BPO is caused partly by 1-adrenoceptor-mediated prostatic smooth muscle con traction and this is the rationale for -adrenoceptor blocker treatment for symptomatic BP O. There are two broad subtypes of -adrenoceptor (AR) \200\224 1 and 2. Molecular cloning studies have identi \201 ed three 1-AR subtypes \200\224 1a (predominant in human stro ma and, therefore, mediates prostate smooth muscle contraction), 1b (predominant in human prostate epithelium), and 1L (believed to be a conformational state of the 1a-AR). The AR subtypes mediating ef \201 cacy and side effects of -adrenoceptor blocking drugs are unknown. Alpha blocker classi \201 cation Alpha blockers are categorized by their selectivity for t he AR and by their elimination half-life. \200 Non-selective: phenoxybenzamine \200\224effective symptom control, but high side effect pro \201 le. \200 1: prazosin, alfuzosin, indoramin. \200 \200 1: terazosin, doxazosin, alfuzosin SR. Long-acting Subtype selective: tamsulosin \200\224relatively selective for compared to the 1b subtype. 1a-AR subtype No study has directly compared one alpha blocker with another in terms of ef \201 cacy or side effects. Terazosin and doxazosin require dose titration to minimize dizziness and sync ope at the start of treatment. Indications for treatment Bothersome LUTS where watchful waiting has failed or the patient wishes to have treatment. Ef \201 cacy Percentage of patients who respond to alpha blockers Patients are able to per ceive a 4-point improvement in IPSS. If \200\230response \200\231 is de \201 ned as >25% improvement in symptoms relative to placebo, most studies describe response rates of 30 \200\22340%.1 The mean probability for improvement in symptom score after TURP is in the or der of 80% (i.e. 8 out of 10 men will notice an improvement in their symptoms after TURP). For those men who respond, the alpha blockers have a much more rapid onset than do the 5 - reductase inhibitors. Their effect will be maximal within a month of starting treatment. Improvements in symptom score in men who \200\230respond \200\231 to alpha blockers The av erage improvement in symptom score after TURP is about 85%.2 While some of this may represe nt a placebo response, this improvement is considerably better than that seen with the alph a blockers, which result in a 10 \200\22330% improvement in symptom score relative to place bo.3 This equates to a 4 \200\2235 points \200\231 improvement in symptom score over placeb o. MEDICAL MANAGEMENT OF BPH: ALPHA BLOCKERS 87 Side effects A substantial proportion of men stop taking their medication either because of side effects (15 \200\22330% report some constellation of side effects) or because of a pe rceived lack of effectiveness (approximately 50% of men stop taking an alpha blocker within 3y because of a perception that it has not worked).4 Side effects include asthenia (weakne ss in 5%), dizziness (2 \200\22314%), headache (2%) and postural hypotension (1%), and retr ograde ejaculation (8%). There is little data on the safety of concomitant use of the alpha blockers with drugs for erectile dysfunction.1 Intraoperative \202 oppy iris syndrome (IFIS) and alpha blocker use A triad of progressiv e intraoperative miosis (constriction of the pupil) despite preoperative dilation, billowin g of a \202 accid iris, and iris prolapse toward the incision site during cataract surger y lead to complications such as posterior capsule rupture with vitreous loss and post-opera tive intraocular pressure spikes (visual acuity outcomes appeared preserved). The original report linked this condition with the preoperative use of tamsulosin; iris dilator smooth m uscle inhibition has been suggested as a potential mechanism.5,6 Risk of IFIS among men taking tamsulosin is substantial (43 \200\22390% in ten retrospectiv e and prospective studies).7 The risk of IFIS appears to be lower with older, generic alpha blockers such as terazosin and doxazosin (0 \200\22325%).7 Whether stopping alpha blocker treatment at any time before surgery mitigates the risk of I FIS is unclear. The AUA 2010 BPH Guidelines7 rec- ommend that men with LUTS secondary to BP H where alpha blocker therapy is planned should be asked about planned cataract surgery. Th ose with planned cataract surgery should avoid the initiation of alpha blockers until their cataract surgery is completed. 1 Lowe F (1999) Alpha-1-adrenoceptor blockade in the treatment of benign prostatic hyperpla sia. Prostate Cancer and Prostatic Diseases 2:110 \200\2239. 2 McConnell JD, Barry MD, Bruskewitz RC, et al. (1994) The BPH Guideline Panel. Benign Pros tatic Hyperplasia: diagnosis and treatment. Clinical Practice Guideline. Agency for Health Care Policy and Research, publication No.94 \200\2230582, 1994, Rockville, Maryland. Public Health Service, US Department of Health and Human Sciences. 3 Boyle P, Robertson C, Manski R, et al. (2001) Meta-analysis of randomized trials of teraz osin in the treatment of benign prostatic hyperplasia. Urology 58:717 \200\22322. 4 de la Rosette, Kortmann B, Rossi C, et al. (2002) Long term risk of retreatment of patien ts using alpha blockers for lower urinary tract symptoms. J Urol 167:1734 \200\2239.