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. 5 Chang D, Campbell J (2005) Intraoperative \202 oppy iris syndrome associated with tamsu losin. J Cataract Refract Surg 31:664. 6 Bell C, Hatch WV, Fischer HD, et al. (2009) Association between tamsulosin and serious op h- thalmic adverse events in older men following cataract surgery. JAMA 301:1991 \200\2236. 7 American Urological Association (2010) The AUA 2010 BPH Guidelines [online]. Available fr om: M http://www.auanet.org. CHAPTER 4 Bladder outlet obstruction 88 Medical management of BPH: 5 -reductase inhibitors 5 -reductase inhibitors inhibit the co nversion of testosterone to DHT, the more potent androgen in the prostate. This causes shri nkage of the pro- static epithelium and, therefore, a reduction in prostate volume, thereby reducing the \200\230static \200\231 component of BPE. This takes some months to occur so urinary symptoms will not improve initially. Finasteride is a competitive inhibitor of the enzyme 5 -reductase (type II isoenzyme), which converts testosterone to DHT. Finasteride, therefore, lowers serum and intrapros- tatic DHT levels. Epristeride is a dual inhibitor o f 5 -reductase. Whether it has any clinically signi \201 cant advantages over \201 nast eride remains to be established. Ef \201 cacy \200 Finasteride: improvement over placebo in the order of 2 \200\2233 points on the IPSS and im provements in \202 ow rate in the order of 1 \200\2232mL/s (SCARP1 (Scandinavian BPH Stud y Group), PROSPECT2 (Proscar safety plus ef \201 cacy Canadian two-year study), PROWESS St udy Group,3 and more recently, PLESS4 (Proscar long-term ef \201 cacy and safety study)). The PLESS data also show a small reduction in the risk of urinary retention. Dutasteride: e vidence for its ef \201 cacy is derived from a 2y RCT with an open-label extension;6 SMART 1, which evaluated the effect of a placebo-controlled withdrawal of an alpha blocker from a combination therapy arm;7 and from the CombAT study (comparison of dutasteride vs tamsulo sin vs dutasteride + tamsulosin).8 a number of large studies have shown symptom Side effects Generally speaking, fairly mild. Principally center around sexual problems (e. g. loss of libido, 5%; impotence, 5%; reduced volume of ejaculate in a few percent). 5 -re ductase inhibitors and the risk of urinary retention The PLESS data5 have been widely publi cized as showing a substantial reduction in the risk of urinary retention. In this 4y follo w-up study, 42 of 1471 men on \201 nasteride went into urinary retention (3%) while 99 of 1404 on placebo experienced an episode of retention (7%). This represents an impressive 43 % relative reduction in risk in those taking \201 nasteride. However, the absolute risk r eduction over a 4y period is a less impressive 4%. So \201 nasteride does reduce the risk of retention, but it is reducing the risk of an event which is actually quite rare, as sug gested by the fact that 93% of men on placebo in this study did not experience retention ov er a 4y period. Put another way, to prevent one episode of retention, 25 men would have to continue treatment with \201 nasteride for 4y. MEDICAL MANAGEMENT OF BPH: 5 -REDUCTASE INHIBITORS 89 5 -reductase inhibitors for haematuria due to BPH Finasteride suppresses vascular endothel ial growth factor (VEGF). Shrinking large vascular prostates probably helps reduce the freq uency of haematuria in men with BPH.5 1 Andersen JT, Ekman P, Wolf H, et al. (1995) Can \201 nasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Stu dy Group. Urology 46:631 \200\2237. 2 Nickel J, Fradet Y, Boake RC, et al. (1996) Ef \201 cacy and safety of \201 nasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial ( the PROSPECT study). PROscar Safety Plus Ef \201 cacy Canadian Two Year Study. Can Med Ass oc J 155:1251 \200\2239. 3 Marberger MJ (1998) Long-term effects of \201 nasteride in patients with benign prostat ic hyper- plasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Grou p. Urology 51:677 \200\22386. 4 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. 5 Foley SJ, Soloman LZ, Wedderburn AW, et al. (2000) Finasteride for haematuria due to BPH. A prospective study of the natural history of hematuria associated with BPH and the effect of \201 nasteride. J Urol 163:496 \200\2238. 6 Roehrborn C, Lukkarinen O, Mark S, et al. (2005) Long-term sustained improvement in symp- toms of benign prostatic hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of 4-year studies. BJU Int 96:572 \200\2237. 7 Barkin J, Guimaraes M, Jacobi G, et al. (2003) Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase in hibitor dutasteride. Eur Urol 44:461 \200\2236. 8 Roehrborn C, Siami P, Barkin J, et al. (2008) The effects of dutasteride, tamsulosin and com- bination therapy on lower urinary tract symptoms in men with benign prostatic hyperpla sia and prostatic enlargement: 2-year results from the CombAT study. J Urol 179:616. CHAPTER 4 Bladder outlet obstruction 90 Medical management of BPH: combination therapy A combination of an alpha blocker and a 5 - reductase inhibitor. The studies: \200 (Medical Therapy of Prostatic Symptoms):1 3047 men; MTOPS study mean prostate volume 36mL. This combination prevented progression of BPH when c ompared with either drug alone (progression being de \201 ned as a worsening of symptom sc ore by 4 or more or the development of complications such as UTI or acute urinary retention ). 2 1200 men randomized Veterans Affairs Combination Therapy Study: to placebo, \201 nas teride, terazosin, or both terazosin and \201 nasteride. At 1y follow-up, relative to pla cebo, \201 nasteride had reduced the symptom score by an average of 3 points whereas tera zosin alone or in combination with \201 nasteride had reduced the symptom score by an ave rage of 6 points. (Prospective European Doxazosin and Combination PREDICT study Therapy):3 randomized >1000 men to placebo, \201 nasteride, doxazosin, or both \201 nasteride and doxazosin. Difference in symptom score at baseline and 1y were: placebo \200\2235.7, \201 nasteride \200\2236.6, doxazosin \200\2238.3, combination therapy \200\2238.5. ALFI N study (alfuzosin, \201 nasteride, and combination in the treatment of BPH):4 1000 men r andomized to alfuzosin, \201 nasteride, or both. At 6 months, the improvement in the IPSS was not signi \201 cantly different in the alfuzosin vs the combination group. CombAT tam sulosin, dutasteride, and a combination of both. Prostate volume was >30mL (TRUS). Only 2y data are available as of 2011. Combination therapy resulted in signi \201 cantly greater i mprovements in symptoms compared to dutasteride from month 3 and tamsulosin from month 9 an d signi \201 cantly greater improvement in peak urinary \202 ow from month 6. There was a signi \201 cant increase in drug-related adverse events with combination therapy. Analys is of the primary endpoints (4y progression of LUTS, urinary retention, and need for prosta te surgery) are awaited. trial.8 4844 men; mean prostate volume 55mL. Compared Thus, most studies, except for MTOPS, suggest that combination therapy is no more useful th an an alpha blocker alone. Disadvantages of combi- nation therapy \200\224greater risk of s ide effects, no additional bene \201 t over alpha blockers alone in most men, need for tre atment for >1y before an improvement in symptoms is seen, sexual side effects. In the Prostate Cancer Prevention Trial,5 18 000 men were randomized to \201 nasteride or placebo over a 7y period. Those in the \201 nasteride group had a lower prevalence of pr ostate cancer detected on prostate biopsy (26.5% of men receiving \201 nasteride had a po sitive biopsy v 29.5% in the placebo group). However, higher-grade tumors (i.e. biologicall y more aggressive than low-grade cancers) were more common in the \201 nasteride group (t here was a 1.3% increase in high-grade cancers in the \201 nasteride group). The jury is out on whether \201 nasteride causes higher-grade cancers MEDICAL MANAGEMENT OF BPH: COMBINATION THERAPY 91 or whether these \201 ndings are a histological or sampling artifact. Finasteride increas es the ability (increased sensitivity) of both PSA, DRE, and prostate biopsy to diagnose hi gh-grade prostate cancer6,7 \200\224so-called cytoreduction of the prostate, leading to a g reater likelihood of \201 nding high-grade cancer (the argument is that \201 nasteride has less of an effect on PSA reduction in men with high-grade than low-grade cancers, so me n with high-grade cancer are more likely to have an elevated PSA and therefore, to undergo prostate biopsy and thus cancer detection). 1 McConnell JD, Roehrborn CG, Bautista OM, et al. (2003) The long-term effect of doxazosin, \201 nasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. New Engl J Med 349:2387 \200\22398. 2 Lepor H, Williford WO, Barry MJ, et al. (1996) The ef \201 cacy of terazosin, \201 nas teride, or both in benign prostatic hypertrophy. N Engl J Med 335:533 \200\22339. 3 Kirby RS, Roerborn C, Boyle P, et al. (2003) Ef \201 cacy and tolerability of doxazosin and \201 nas- teride, alone or in combination, in treatment of symptomatic benign prostat ic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Urology 61:119 \200\22326. 4 Debruyne FM, Jardin A, Colloi D, et al. (1998) Sustained-release alfuzosin, \201 naster ide and the combination of both in the treatment of benign prostatic hyperplasia. Eur Urol 34:169 \200\22375. 5 Thompson IM, Goodman PJ, Tangen CM, et al. (2003) The in \202 uence of \201 nasteride on the development of prostate cancer. N Engl J Med 349:215 \200\22324. 6 Thompson IM, Chi C, Ankerst DP, et al. (2006) Effect of \201 nasteride on the sensitivi ty of PSA for detecting prostate cancer. J Natl Cancer Inst 98:1128. 7 Thompson IM, Tangen CM, Goodman PJ, et al. (2007) Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection. J Urol 177:1749. 8 Roehrborn C, Siami P, Barkin J, et al. (2008) The effects of dutasteride, tamsulosin and com- bination therapy on lower urinary tract symptoms in men with benign prostatic hyperpla sia and prostatic enlargement: 2-year results from the CombAT study. J Urol 179: 616. CHAPTER 4 Bladder outlet obstruction 92 Medical management of BPH: alternative drug therapy Anticholinergics For a man with frequen cy, urgency, and urge incontinence \200\224symptoms suggestive of an overactive bladder \200\224consider prescribing an anticholiner- gic (e.g. oxybutynin, tolterodine, trospium c hloride, or \202 avoxate). There is the concern that these drugs could precipitate urinar y retention in men with BOO (because they block parasympathetic/cholinergic-mediated contra ction of the detrusor), but the risk of this occurring is probably very low, even in men wi th urodynamically proven BOO.1 Phytotherapy An alternative drug treatment for BPH symptoms and one which is widely used in Europe and increasingly in North America is phytotherapy. Fifty percent of all medications consumed for BPH symptoms are phytothera- peutic ones.2 Examples include the Saw palmetto plant (Serenoa repens) and extracts from the stinging net tle (Urtica dioica), among several others. While previ- ous editions of this book quoted st udies, including a meta-analysis, that suggested similar ef \201 cacy to 5ARs in terms of improvements in symptoms and \202 ow rates,2,3 more recent studies have generally failed to con \201 rm a clinically important role for Saw palmetto in the management of BPH.4,5 NICE in the UK does not recommend phytotherapy for LUTS in men (M www.nice.org.uk/CG97) and similarly, in the United States, phyto- therapy is no longer recommended by the AUA 2010 B PH Guidelines (M http://www.auanet.org). 1 Reynard J (2004) Does anticholinergic medication have a role for men with lower urinary t ract symptoms/benign prostatic hyperplasia either alone or in combination with other agents ? Curr Opin Urol 14:13 \200\2236. 2 Wilt T, Ishani A, Stark G, et al. (1998) Saw palmetto extracts for treatment of benign pr ostatic hyperplasia: a systematic review. JAMA 280:1604 \200\2238. 3 Wilt T, Ishani A, Rutks I, et al. (2000) Phytotherapy for benign prostatic hyperplasia. P ublic Health Nutr 3:459. 4 Bent S, Kane C, Shinohara K, et al. (2006) Saw palmetto for benign prostatic hyperplasia. N Engl J Med 354:557 \200\22366. 5 Shi R, Xie Q, Gang X, et al. (2008) Effect of saw palmetto soft gel capsule on lower urin ary tract symptoms associated with benign prostatic hyperplasia: a randomized trial in Shan ghai, China. J Urol 179:610. This page intentionally left blank CHAPTER 4 Bladder outlet obstruction 94 Minimally invasive management of BPH: surgical alternatives to TURP In 1989, Roos reported a seemingly higher mortality and reoperation rate after TURP when compared with open prosta tectomy.1 This, combined with other studies suggesting that symptomatic outcome after TURP was poor in a substantial proportion of patients and that TURP was asso- ciated with substa ntial morbidity, prompted the search for less invasive treatments. The two broad categories of alternative surgical techniques are mini- mally invasive and in vasive. All are essentially heat treatments, delivered at variable temperature and power an d producing variable degrees of coagulative necrosis (minimally invasive) of the prostate o r vaporization of prostatic tissue (invasive). For those practicing in the UK, note that the 2010 NICE Guidelines (M www.nice.org.uk/CG97) recommend that TUNA, TUMT, and HIFU should not be offered as alternatives to TURP, TUVP, o r HoLEP. These techniques are used in other countries, hence a discussion of the various te chniques here. Transurethral radiofrequency needle ablation (TUNA) of the prostate Low-level radiofrequenc y is transmitted to the prostate via a transure- thral needle delivery system; the needles which transmit the energy are deployed in the prostatic urethra once the instrument has bee n advanced into the prostatic urethra. It is done under local anesthetic, with or with- out intravenous sedation. The resultant heat causes localized necrosis of the prostate. Improvements in symptom score and \202 ow rate are modest. Side effects include bleeding (one third of patients), UTI (10%), and urethral stric- ture (2%). No adverse effects on se xual function have been reported.2 Concerns remain with regard to long-term effectiveness. Transurethral microwave thermotherapy (TUMT) Microwave energy can be delivered to the prost ate via an intraurethral cath- eter (with a cooling system to prevent damage to the adjacen t urethra), producing prostatic heating and coagulative necrosis. Subsequent shrink- age of the prostate and thermal damage to adrenergic neurons (i.e. heat- induced adrenergic nerve block) relieves obstruction and symptoms. Many reports of TUMT treatment are open studies, all patients receiv- ing treatment (no \200\230sham \200\231 treatment group where the microwave catheter is inserted, but no micr owave energy is given \200\224this results in 10-point symptom improvements in approximatel y 75% of men). Compared with TURP, TUMT results in symptom improvement in 55% of men and TU RP in 75%. Sexual side effects after TUMT (e.g. impotence, retrograde ejaculation) are less frequent than after TURP, but catheterization period is longer and UTI and irritative urin ary symptoms are more common.3 EAU Guidelines state that TUMT \200\230should be reserved f or patients who prefer to avoid surgery orwho no longer respond favorably to medication \200\231. TUMT is still a popular treatment in the United States. MINIMALLY INVASIVE MANAGEMENT OF BPH 95 High intensity focused ultrasound (HIFU) A focused ultrasound beam can be used to induce a rise in temperature in the prostate or indeed in any other tissue to which it is applied. F or HIFU treatment of the prostate, a transrectal probe is used. A general anaes- thetic or heavy intravenous sedation is required during the treatment. It is regarded as an investiga tional therapy. 1 Roos NP, Wennberg J, Malenka DJ, et al. (1989) Mortality and reoperation after open and t ransurethral resection of the prostate for benign prostatic hyperplasia. New Engl J Med 320 :1120 \200\2234. 2 Fitzpatrick JM, Mebust WK (2002) Minimally invasive and endoscopic management of benign p rostatic hyperplasia. In Walsh PC, Retik AB, Vaughan ED, Wein AJ (eds) Campbell \200\231s U rology, 8th edn. Philadelphia: Saunders. 3 D \200\231Ancona FCH, Francisca EAE, Witjes WPJ, et al. (1998) Transurethral resection of the prostate vs high-energy thermotherapy of the prostate in patients with benign prostati c hyperplasia: long-term results. Br J Urol 81:259 \200\22364. CHAPTER 4 Bladder outlet obstruction 96 Invasive surgical alternatives to TURP Transurethral electrovaporization of the prostate (T UVP) Vaporizes and dessicates the prostate. TUVP seems to be as effective as TURP for sympt om control and relief of BOO, with durable (5y) results. Operating time and inpatient hospi tal stay are equivalent. Requirement for blood transfusion may be slightly less after TUVP. 1,2 TUVP does not provide tissue for histological examination so prostate cancers cannot be detected. NICE in the UK has endorsed TUVP as a surgical treatment option for prostatic sy mptoms.3 Laser prostatectomy Several different techniques of \200\230laser prostatectomy \200\231 e volved during the 1990s. Essentially, in the year 2012, we are left with just holmium laser prostatectomy (endorsed by NICE 2010 Guidelines) and the green light laser (NICE 2010 Guid elines recommending its use only in the context of RCTs).3 Transurethral ultrasound-guided laser-induced prostatectomy (TULIP) Performed using a probe consisting of a Nd:YAG laser adjacent to an ultra- sound transducer. Visual laser ablation of the prostate (VLAP) This side- \201 ring system used a mirror to re \202 ect or a prism to refract the laser energy at various angles (usually 90 ) from a laser \201 bre located in the prostatic urethra onto the surface of the prostate. The pr incipal tissue effect was one of coagulation with subsequent necrosis. Contact laser prostatectomy Produces a greater degree of vaporization than VLAP, allowing t he immediate removal of tissue. Interstitial laser prostatectomy (ILP) Performed by transurethral placement of a laser \201 bre directly into the prostate that produces a zone of coagulative necrosis some dista nce from the prostatic urethra. TULIP, VLAP, contact laser prostatectomy, and ILP have been suc- ceeded by holmium laser prostatectomy. KTP laser vaporization of the prostate Also known as \200\230greenlight \200\231 photosele ctive vaporization of the prostate (PVP). A ytrium-aluminum-garnet (YAG) laser light is sho ne through a potassium titanyl phosphate (KTP) crystal, doubling the frequency and halving the emitted light wavelength to 532nm. This is in the green part of the visible spectrum an d is strongly absorbed by hemoglobin, produc- ing ef \201 cient prostate tissue vaporizati on (Fig. 4.1). KTP energy is poorly absorbed by water/saline (the irrigant) and therefore, a non-contact vaporization is possible. The bene \201 ts include less heating of the deliv ery \201 bre, which can last for a longer period of time. Laser systems of 80 and 120W ar e available. In the 80W system, approximately 100kJ will be deliv- ered to the average pros tate in 30min by rapid pulses of \200\230quasi-continuous \200\231 INVASIVE SURGICAL ALTERNATIVES TO TURP 97 energy. Laser heat is concentrated over a small area, which allows rapid vaporization of ti ssue with minimal coagulation of underlying structures (2mm rim of coagulated tissue is lef t), but creating effective haemostasis. It can be used for larger prostates (>100mL)4 and h igher risk patients on anticoagulants.5 Indications The 2010 NICE Guidelines on Management of LUTS in men state that laser vaporiza tion techniques, of which greenlight laser is one, should be offered only as part of an RCT .6 Technique Using a KTP/532 80W laser (Laserscope ), a 6F side- \201 ring \201 bre is pla ced through a 24F continuous irrigation cystoscope, with normal saline irriga- tion. Genera lly, the median lobe is treated \201 rst, then the lateral lobes, using a sweeping moveme nt of the laser \201 bre across the prostate, starting at the bladder neck and working di stally to the level of the verumontanum. No tissue is available for histology. Advantages over TURP KTP laser prostatectomy can be performed safely as a day surgery opera tion, and in selected cases, a catheter may not be needed post-operatively or can be remove d within 24h. It provides a virtually bloodless operation with no reported need for blood t ransfusion, even in anticoagulated patients. Irrigation with saline or water avoids the ris k of transurethral resection (TUR syndrome. The incidence of retrograde ejaculation is lowe r than TURP (8.3 \200\22352%),7,8 with no reported cases of new erectile dysfunction. When directly compared to TURP, equivalent short-term ef \201 cacies are seen, but with signi \201 cantly shorter catheterization times and inpatient stays in the laser group.9,10 Outcomes Short- and medium-term outcomes (up to 5y follow-up) demonstrate sus- tained and s tatistically signi \201 cant improvements in symptom scores (IPSS/ AUA), \202 ow rate, a nd post-void residual volumes.7 \200\22312 Post-operative complications Haematuria (1 \200\22311%); dysuria (2 \200\22321%); acute uri nary retention (1 \200\22311%); reoperation rate (0 \200\2235% at 1y). Holmium (Ho): YAG laser The holmium laser is a pulsed solid state laser with a wavelength o f 2140nm which is strongly absorbed by water. It is absorbed into prostate tissue to a dept h of 0.4mm and the heat created (>100 C) causes good tissue vaporization, whilst causing c oagulation of small to medium-sized blood vessels. The coagulative depth is about 2 \200 \2233mm beyond the tissue that has been vaporized. The irrigant is normal saline so the ris k of TUR syndrome is avoided. Holmium laser enucleation of the prostate (HoLEP) (endorsed by 2010 NICE Guidelines on mana gement of LUTS in men M www.nice.org.uk/CG97) HoLEP is particularly useful for treating lar ger prostates. An end- \201 ring laser \201 bre is used to cut grooves into the prostate down to the level of the capsule. The prostate lobes are then dissected off and pushed int o the CHAPTER 4 Bladder outlet obstruction 98 KTP/532nm (GreenLight PV) 10,000.00 1,000.00 Diode 830nm (ILC, Indigo ) ) m c / 1 ( 100.00 t n e c i f f e o C n o i t p r o s b A 10.00 i Water Oxyhemoglobin 1.00 0.10 Ho:YAG, Holmium 2100nm (HoLEP & HoLAP) 0.01 Nd:YAG 1064 nm (VLAP 0.001 0.0001 14001600 1800 2000 200 400 600 800 10001200 Wavelength (nm) Fig. 4.1 Absorption curve of water and oxyhaemoglobin. From Laserscope Physician training manual 2006. (Reproduced with permission from the American Medical Systems Inc, Minnesota. ) bladder where a mechanical morcellator is used to fragment and aspirate the tissue. HoLEP i s technically more dif \201 cult to master than laser vapori- zation and has a longer lear ning curve, but the overall results are at least equivalent to TURP with fewer associated r isks. In a randomized trial comparing holmium laser enucleation with TURP for prostates >40g, HoL EP was equivalent to TURP, but with those in the HoLEP group having a shorter catheterizati on time and hospital stay. A larger volume of prostatic tissue was removed.13 Long-term fol low-up (7y) demonstrates sustained signi \201 cant improvements in symptom scores and \202 ow rates.14 In a direct comparison with open prostatectomy, HoLEP has also demonstrate d equivalent improvement in symptom scores and \202 ow rates at 3y follow-up.15 Other techniques of holmium laser prostatectomy Holmium laser ablation of the prostate (HoL AP) A side- \201 ring dual wavelength \201 bre is used in a near-contact mode to vaporiz e prostatic tissue circumferentially to produce a satisfactory chan- nel. Original techniqu es used 60W lasers, however, lasers up to 100W are now available. Symptom improvements are sustained in the long term,16 and when directly compared with TURP, similar ef \201 cacy w as seen in the short term, but with shorter hospital stay and catheter times in the HoLAP g roup and less bleeding than for TURP.17 Studies suggest overall, it is most effective for s maller prostate glands. Holmium laser resection of the prostate (HoLRP) This technique copies that of TURP, whereby the precise cutting ability of the holmium laser is used to remove pieces of prostate down to the capsule to create a large and relatively bloodless channel. It can be used INVASIVE SURGICAL ALTERNATIVES TO TURP 99 on prostate glands of all sizes. Again, it has short catheterization times and hospital sta ys and is associated with minimal post-operative dysuria.18 1 Hammadeh MY, Madaan S, Hines J, Philp T (2000) Transurethral electrovaporization of the p rostate after 5 years; is it effective and durable? BJU Int 86:648 \200\22351. 2 Mc Allister WJ, Karim O, Plail RO, et al. (2003) Transurethral electrovaporization of the prostate: is it any better than conventional transurethral resection of the prostate? BJU Int 91:211 \200\2234. 3 National Institute for Health and Clinical Excellence (2010) The management of lower urin ary tract symptoms in men [online]. Available from: M www.nice.org.uk/CG97. 4 Sandhu JS, Ng C, Vanderbrink BA, et al. (2004) High-power potassium-titanyl-phosphate pho toselective laser vaporization of prostate for treatment of benign prostatic hyperplasia in men with large prostates. J Urol 64:1155 \200\2239. 5 Sandhu JS, Ng CK, Gonzalez RR, et al. (2005) Photoselective laser vaporization prostatect omy in men receiving anti-coagulants. J Endourol 19:1196 \200\2238. 6 National Institute for Health and Clinical Excellence (2010) The management of lower urin ary tract symptoms in men [online]. Available from: M www.nice.org.uk/CG97. 7 Sandhu JS, Ng CK, Gonzalez RR, et al. (2005) Photoselective laser vaporization prostatect omy in men receiving anti-coagulants. J Endourol 19:1196 \200\2238. 8 Sarica K, Alkan E, L leci H, et al. (2005) Photoselective vaporization of the enlarged p rostate with KTP laser: long-term results in 240 patients. J Endourol 19:1199 \200\223202. 9 Bachmann A, Sch rch L, Ruszat R, et al. (2005) Photoselective vaporization (PVP) versus transurethral resection of the prostate (TURP): a prospective bi-center study of perioperat ive morbidity and early functional outcome. Eur Urol 48:965 \200\22372. 10 Bouchier-Hayes DM, Anderson P, Van Appledorn S, et al. (2006) KTP laser versus transure- thral resection: early results of a randomized trial. J Endourol 20:580 \200\2235. 11 Sandhu JS, Ng C, Vanderbrink BA, et al. (2004) High-power potassium-titanyl-phosphate ph otoselective laser vaporization of prostate for treatment of benign prostatic hyperplasia i n men with large prostates. J Urol 64:1155 \200\2239. 12 Malek RS, Kuntzman RS, Barrett DM (2005) Photoselective potassium-titanyl-phosphate lase r vaporization of the benign obstructive prostate: observations on long-term outcomes. J Ur ol 174:1344 \200\2238. 13 Wilson LC, Gilling PJ, Williams A, et al. (2006) A randomized trial comparing holmium la ser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years. Eur Urol 50:569 \200\22373. 14 Elzayat EA, Habib EI, Elhilali MM (2005) Holmium laser enucleation of the prostate: a si ze-independent new \200\230gold standard \200\231. Urology 66:108 \200\22313. 15 Kuntz RM, Ahyai S, Lehrich K (2006) Transurethral holmium laser enucleation of the pros- tate compared with transvesical open prostatectomy: 3 years follow-up of a randomized tria l. Proc SPIE 6078:11. 16 Tan AHH, Gilling PJ, Kennett KM, et al. (2003) Long-term results of high-power holmium l aser vaporization (ablation) of the prostate. BJU Int 92:707 \200\2239. 17 Mottet N, Anidjar M, Bourdon O, et al. (1999) Randomized comparison of transurethral ele c- troresection and holmium:YAG laser vaporization for symptomatic benign prostatic hyperpl asia. J Endourol 13:127 \200\22330. 18 Gilling PJ, Cass CB, Cresswell MD, et al. (1996) The use of holmium laser in the treatme nt of benign prostatic hyperplasia. J Endourol 5:459-61. CHAPTER 4 Bladder outlet obstruction 100 TURP and open prostatectomy TURP Removal of the obstructing tissue of BPH or obstructing pr ostate can- cer from within the prostatic urethra, leaving the compressed outer zone intact (the \200\230surgical capsule \200\231). An electrically heated wire loop is used, throug h a resectoscope, to cut the tissue and diathermy bleeding vessels. The cut \200\230chips \200\231 of prostate are pushed back into the bladder by the \202 ow of irrigating \202 uid and at the end of resection, are evacuated using specially designed \200\230evacuator s \200\231 \200\224a plastic or glass chamber attached to a rubber bulb which allows \202 uid to be \202 ushed in and out of the bladder. Indications for TURP \200 Bothersome LUTS that fail to respond to changes in lifestyle or medical therapy. Recurrent acute urinary retention. Renal impairment due to BOO (high-pressure retention). Recurrent h aematuria due to BPE. Bladder stones due to prostatic obstruction. \200 chronic urinary \200 Open prostatectomy Indications \200 \200 \200 \200 \200 Large prostate (>100g). TURP not technically possible (e.g. limited hip abduction). Failed TURP (e.g. because of bleeding). Urethra too long for the resectoscope to gain access to th e prostate. Presence of bladder stones which are too large for endoscopic cystolitholapaxy, combined with marked enlargement of the prostate. Contraindications \200 \200 Small \201 brous prostate. Prior prostatectomy in which most of the gland has been resect ed or removed; this obliterates the tissue planes. Carcinoma of the prostate. Techniques Suprapubic (transvesical) The preferred operation if enlargement of the prostate involves mainly the middle lobe. The bladder is opened, the mucosa around the protruding a denoma is incised, and the plane between the adenoma and capsule is developed to enucleate the adenoma. A 22 Ch urethral and a suprapubic catheter are left, together with a retropubi c drain. Remove the urethral catheter in 3 days and clamp the suprapubic at 6 days, removin g it 24h later. The drain can be removed 24h after this (day 8). Simple retropubic Popularized by Terence Millin (Ireland, 1947). Compared with the suprapu- bic (transvesical) approach, it allows more precise anatomic exposure of the prostate, thu s giving better visualization of the prostatic cavity, which allows more accurate removal o f the adenoma, better control of bleeding TURP AND OPEN PROSTATECTOMY 101 points, and more accurate division of the urethra so reducing the risk of incontinence. As well as the contraindications noted, the retropubic approach should not be employed when the middle lobe is very large because it is dif \201 cult to get behind the middle lobe a nd so to incise the mucosa (safely) distal to the ureters. The prostate is exposed by a Pfannenstiel or lower midline incision. Haemostasis is achieve d before enucleating the prostate by ligating the dorsal vein complex with sutures placed d eeply through the prostate. The prostatic capsule and adenoma are incised transversely with the dia- thermy just distal to the bladder neck. The plane between the capsule and adenoma is found with scissors and developed with a \201 nger. Sutures are used for haemostasis. A wedge of bladder neck is resected. A catheter is inserted and left for 5 days and the tr ansverse capsular incision is closed. A large tube drain (30Ch Robinson \200\231s) is left for 1 \200\2232 days. Complications \200 \200 \200 Hemorrhage. Urinary infection. Rectal perforation (close and cover with a colostomy). CHAPTER 4 Bladder outlet obstruction