Minimally InvasiveTreatment of BPH: An Update

Transcription

1 EAU Update Series 2 (2004) Minimally InvasiveTreatment of BPH: An Update Anton Ponholzer, Martin Marszalek, Stephan Madersbacher * Department of Urology and Andrology, Ludwig Boltzmann Institute for Urological Oncology, Donauspital, Langobardenstrasse 122, A-1220 Vienna, Austria Abstract Objectives: Aim of this review is provide updated information regarding the current role of minimally invasive treatment (MIT) for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO). Methods: We reviewed the literature and report on the statements of BPH guidelines released by the European Association of Urology (EAU) and the American Urological Association (AUA). We largely concentrate on randomised clinical trials (RCT) and long-term follow-up series (12 months). Results: When assessing the current role of MIT a number of parameters, such as the need for anaesthesia, intra- and postoperative complications, morbidity, short- and long-term outcome have to be considered. MIT can be divided into (i) thermal-based therapies, (ii) laser therapies, (iii) ablative therapies and (iv) other technologies. The currently most attractive MITs are high-energy TUMT, Holmium-laser enucleation and transurethral electrovaporisation. Conclusions: BPH guidelines such as those of the EAU and AUA give clear recommendations in this evolving field. MITs not considered established by BPH guidelines should not be used outside clinical trials. # 2004 Elsevier B.V. All rights reserved. Keywords: Lower urinary tract symptoms; Prostate; Treatment; Outcome 1. Introduction For decades transurethral resection of the prostate (TURP) was the undisputed gold standard therapy for patients with severe lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) [1]. Within the past 15 years the role of TURP has been increasingly challenged by the development of medical therapies and minimal invasive treatments (MITs) [1]. The main driving forces behind this development were the high prevalence of the disease, an absolute indication for surgery in only 20 30% of patients, the rather unchanged postoperative morbidity of TURP and recent technical innovations [1]. Aim of this review is to provide updated information regarding the current role of MIT for the treatment of LUTS due to BPO. To achieve this goal and to present as much as possible evidence-based data we concentrate on the results of randomised clinical trials (RCT), * Corresponding author. Tel. þ ; Fax: þ addresses: madersbacher@hotmail.com, stephan.madersbacher@wienkav.at (S. Madersbacher). long-term follow-up data and the recommendations of BPH guidelines released by the European Association of Urology (EAU) and the American Urological Association (AUA) [2,3]. Only studies reported in peerreviewed journals were considered, published abstracts were not included Currently available minimally invasive treatment options MIT can be divided into (i) thermal-based therapies, (ii) laser therapies, (iii) ablative therapies and (iv) others. 2. Thermal-based therapies Thermal-based therapies use high temperatures to induce a coagulation necrosis within the prostate. Although microwaves have been the primary energy to heat prostatic tissue, radio frequency waves, highintensity focused ultrasound (HIFU) and hot water have been used as well. A thermal-based therapy that achieves temperatures below 45 8C is referred to ashyperthermia and treatment temperatures above 45 8C are referred to as /$ see front matter # 2004 Elsevier B.V. All rights reserved. doi: /j.euus

2 A. Ponholzer et al. / EAU Update Series 2 (2004) thermotherapy (low-energy thermotherapy: C; high-energy thermotherapy: >60 8C) Transurethral and transrectal hyperthermia Technique: Via a transrectal or transurethral route, therapeutic temperatures of less than 45 8C are generated by microwaves. RCT: Hyperthermia induces only a transient improvement of symptoms, no proof of efficacy in RCT. Long-term data: Not available. Guidelines: Not recommended by the EAU and AUA guidelines [2,3]. This technique is considered obsolete for the indication BPH [2,3] High-intensity focused ultrasound Technique: High-intensity focused ultrasound (HIFU) waves are emitted by a transrectal ultrasound transducer [4]. Within the HIFU-beam focus, therapeutic temperatures in the range of C are generated leading to an immediate coagulative tissue necrosis [4] (Fig. 1). The ultrasound head is moved mechanically in two dimensions to generate a clinically useful tissue necrosis [4]. This treatment requires spinal or general anaesthesia; some patients have been successfully treated under iv-sedation. RCT: No data of RCT available. Long-term data: Madersbacher et al. studied the long-term outcome of 80 patients followed for a mean of 41 months [5]. The Q max increased from preoperatively 9.1 ml/s to 11.8 ml/s after 12 months and gradually declined to 10.2 ml/s (þ12%) after 4 years. Within 4 years, 44% underwent TURP [5]. The retreatment-free period was significantly longer for patients with a pre-treatment average flow rate >5 ml/s and lower grades of urodynamically documented bladder outflow obstruction [5]. Guidelines: EAU and AUA guidelines consider HIFU to be an investigational procedure for the indication BPH, which should not be offered outside the framework of clinical trials [2,3]. Fig. 1. Overview of currently available MIT for BPH. The asterisk () indicates that this treatment is considered investigational according to the EAU guidelines [2].

3 26 A. Ponholzer et al. / EAU Update Series 2 (2004) Water-induced thermotherapy Technique: Water-induced thermotherapy (WIT) consists of a compact microprocessor based on a control console with a water heater, a peristaltic pump and temperature sensors [6] (Fig. 1). The 18 French WIT catheter consists of a treatment balloon inflatable to 50 French within which heated water circulates during therapy and an air inflatable positioning balloon [6] (Fig. 1). Treatment is performed under local anaesthesia, systematic sedoanalgesic medication is not necessary [6]. RCT: No data of RCT are yet available. Long-term data: Muschter et al. performed a singlearm, multicenter trial on 125 patients [6]. At 12 months, the IPSS improved by a median of 12.5 points and the peak flow rate by 6.4 ml/s [6]. Serious adverse events were infrequent. Guidelines: EAU and AUA guidelines consider WIT to be an investigational procedure, which should not be offered outside the framework of clinical trials [2,3] Transurethral needle ablation (TUNA) Technique: TUNA delivers low radio frequency energy directly into selected areas of the prostate through a catheter equipped with adjustable needles thus producing a coagulation necrosis while sparing the urethral mucosa (Fig. 1) [7 9]. Ablation is achieved when the needles reach temperatures of C. The two needles at the catheter tip, which are arranged at an acute angle to each other and to the catheter, can be advanced or retracted through controls on the catheter handle (Fig. 1). The lateral lobes are treated in 2 or 3 planes, starting 1 cm from the bladder neck and proceeding to 1 cm proximal to the seminal colliculus [7 9]. TUNA can be performed under local anaesthesia although it appears that TUNA has a higher requirement for analgesia and sedation than does transurethral microwave thermotherapy (TUMT). RCT: Two RCTs with follow-ups of 12 and 18 months are available [7,8]. Bruskewitz et al. randomised 121 patients to TUNA or TURP [7]. While improvements of the bother score was similar in both groups, changes of symptoms and maximum flow rates were higher in the TURP arm [7]. TUNA had fewer effects on sexual function than TURP [7]. Similar findings were reported in a small-sized RCT of 59 patients followed for up to 18 months [8]. Long-term results: Zlotta et al. reported on the outcome with a follow-up of up to five years from three centres [9]. At a mean follow-up of 63 months, 24% of patients reported on a 50% improvement of Q max and 78% on a 50% improvement of symptoms; 23% of patients required additional BPH treatment after a mean of 63 months. Guidelines: TUNA is effective in partially relieving symptoms of BPH (AUA BPH guidelines) [3]. According to the EAU guidelines clinical efficacy has been proven in RCT, although there is limited evidence of long-term efficacy [2]. Due to a significant treatment failure rate, TUNA is not recommended as a first line treatment for LUTS [2]. Interstitial thermo-coagulation can also be achieved by a simple radio frequency needle inserted through a cystoscope (Interstitial Radio Frequency Therapy [IRFT]) [10]. This technique was evaluated in one RCT against TURP with a follow-up of two years. Although symptomatic improvement was sustained after two years; objective parameters such as post-void residual volume or Q max, however, reached baseline values after two years. IRFT is not specifically mentioned in the EAU and AUA guidelines [2,3] Transurethral microwave thermotherapy Technique: Microwave thermotherapy (TUMT) devices consist of a treatment module that contains a microwave generator with a temperature measurement and a cooling system [11] (Fig. 1). A treatment catheter is connected to the module and inserted into the prostatic urethra. The TUMT catheter consists of a microwave antenna positioned in the tip of the catheter just below the positioning balloon (Fig. 1) [11]. Fluid channels surrounding the catheter provide urethral cooling. Also incorporated in the catheter are one or more temperature sensors. More than 20 microwave systems are on the market; few, however, have been evaluated in RCTs (see AUA guidelines [3]). TUMT is by far the most popular MITwith more than 100,000 patients treated worldwide Low-energy TUMT protocols Low-energy (LE-TUMT) TUMT induces therapeutic temperatures of C. This procedure is well tolerated and the postoperative morbidity minimal. Although low-energy TUMT has proven to be efficient in short-term RCTs, long-term data are disappointing with treatment failure rates in the range of 25 70% after 3 5 years [12]. Due to these poor long-term data low-energy protocols have largely been abandoned from current clinical practice and are therefore not described in more detail herein High-energy (HE) TUMT protocols RCT: Several RCTs comparing TUMT to TURP are available; the respective data are quite reproducible

4 A. Ponholzer et al. / EAU Update Series 2 (2004) [13 17]. In these five RCTs, symptoms improved by a mean of 63%, the Q max by 53% and the post-void residual volume by 32% at 12 months [13 17]. The corresponding numbers for the five TURP arms in these RCTs were 74%, 128% and 78%. Hence, while improvements of symptoms were usually comparable after TUMT and TURP, changes of objective parameters such as uroflowmetry and urodynamic parameters are generally superior after conventional TURP [13 17]. A major advantage of TUMT is the fact that this treatment can be performed under local anaesthesia and that it is a purely outpatient procedure. With the exception of a prolonged period of retention (2 4 weeks) postoperative morbidity is minimal [13 17]. Long-term outcome: Long-term data of uncontrolled studies suggest that the durability of high-energy TUMT is substantially higher than after low-energy TUMT. The re-treatment rate following high-energy TUMT is in the range of 5 15% within one year after treatment [13 17]. Guidelines: The guidelines of the AUA state that the following TUMT devices are effective in partially relieving symptoms in men with BPH: Prostatron TM, Targis TM, Coretherm TM, and TherMatrx TM [3]. There is no evidence of superiority of one device over another [3]. The AUA guidelines emphasise safety recommendations published by the FDA to avoid unexpected procedure-related injuries (e.g. urethral fistulas in patients with previous pelvic irradiation) [3]. According to the EAU guidelines, high-energy TUMT should be reserved for patients who prefer to avoid surgery or who no longer respond favourably to medication [2]. 3. Laser therapy Laser energy can be used to produce coagulation necrosis, vaporisation of tissue, or resection of tissue Visual laser ablation of the prostate (VLAP) Technique: Side-firing laser prostatectomy is generally performed using Nd:YAG laser light at 1064 nm and at a relatively high power setting (40 80 W), delivered via an optical fibre equipped with a distal reflecting mechanism (Fig. 1). Optimal tissue ablation is achieved using long-duration (60 90 seconds) Nd:YAG laser applications to fixed spots along the prostatic urethra (non-contact technique). The coagulated tissue eventually necroses and sloughs ultimately relieving obstruction. Using a contact laser technique, the laser probe directly touches and immediately vaporises tissue, the net result being the immediate removal of obstructing tissue in a manner equivalent to conventional TURP. RCT: To date, a number of RCTs comparing VLAP usually to TURP have been reported [18 25]. These studies have repeatedly shown than VLAP results in similar improvements of symptoms, quality of life indices and uroflow parameters as conventional TURP [18 25]. In these 8 RCTs, symptoms improved by a mean of 64% and peak flow rate by 93% 12 months after VLAP. The respective numbers for the corresponding TURP arms were 71% and 109%. Hence, improvements of symptoms and uroflow parameters were comparable after TURP and VLAP at 12 months. The risk of bleeding and of the TURP syndrome is minimal. Gujral et al. recently reported on an RCT in men with chronic urinary retention. In this indication, TURP was more effective than VLAP in terms of symptom score, maximum flow rate and failure [23]. However, men who underwent resection had significantly more treatment-related complications and were hospitalised longer than those who received laser therapy [23]. The major limitation of VLAP (non-contact technique) compared to conventional TURP is the lack of an immediate clinical effect and requirement for urinary catheter drainage for several postoperative days. Some patients may require catheterisation for 3 4 weeks or more [18 25]. Even after catheter removal, an improvement in voiding occurs only gradually over 4 6 weeks. Best results are achieved in patients with small/moderate-sized prostates. Long-term data: Data of RCTs with follow-ups of 3 and 5 years are available. Although improvements of symptoms and Q max were similar after TURP and VLAP at 3 years, the re-treatment rate at 3 years was substantially higher after VLAP (18%) as compared to TURP (9%) [24]. Keoghane et al. reported on the 5 yrs outcome of the Oxford Laser Prostatectomy Trial [22]. At 5 years, 18% in the laser arm and 14.5% after TURP underwent retreatment [22]. Guidelines: According to the AUA, VLAP results in equivalent short-term improvements in symptom scores, urinary flow rate, and quality of life indices when compared to TURP [3]. The rates of postoperative urinary retention and the need for unplanned secondary catheterisation after VLAP (non-contact technique) appears to be higher than for TURP [3]. The EAU does not recommend VLAP as a first-line surgical treatment for patients with LUTS, but indicates that it may have a role in the treatment of high-risk patient groups [2].

5 28 A. Ponholzer et al. / EAU Update Series 2 (2004) ILC Technique: ILC is based on the creation of an intraprostatic coagulative lesion by laser light at a relatively low power density [17,26]. ILC is performed with a standard cystoscope, a solide state, diode 839 nm laser, and a special fibre-optic delivery system (Fig. 1) [17,26]. Under direct visualisation, the laser fibre is introduced directly into the prostate through a small puncture in the prostatic urethra (Fig. 1). Low-power thermal energy is delivered to coagulate prostatic tissue. The laser fibre can be introduced into any region of the prostate, and the number of sites for the application of energy is dependent on prostate size and configuration of the gland [9,27]. RCT: Two randomised trials with an ILC arm have been reported, both revealing similar results [17,26]. While improvements of symptoms were comparable for TURP and ILC, changes of Q max and PVR were generally less pronounced after ILC [26]. After 24 months, the median Q max after ILC was 13.9 ml/s and after TURP 16.5 ml/s [26]. The difference of post-void residual after 24 months, however, was only 14 ml and of the AUA symptom score only 2 points. There is a temporary increase of obstruction after ILC, postoperative catheterisation is required for an average of up to 18 days, although the catheter was removed within 10 days in more than 70% of cases [26]. Long-term results: Reliable long-term data are not yet available; the re-treatment rate at 12 months is in the range of 5 15%. Guidelines: According to the AUA BPH guidelines there is inadequate evidence to support inclusion of ILC as treatment option [3]. EAU guidelines do not recommend ILC as a first-line surgical treatment for patients with LUTS, yet indicate that ILC may have a role in the treatment of high-risk patients [2] Holmium-Laser Resection Technique: The Holmium (Ho) laser (2140 nm) is a pulsed, solid-state laser, which is strongly absorbed by water [27]. The zone of tissue coagulation in tissue is limited to 2 3 mm, sufficient to obtain adequate haemostasis. Instrumentation for this technique includes a mm end-firing quartz fibre and an W Ho-Laser [27]. The transurethral Holmium-Laser Resection (HoLR) is a relatively new technique in which the prostatic adenoma is mobilised using a Holmium laser fibre (Fig. 1) [27 31]. The mobilised ademona is either morcellated or resected using the mushroom technique [27 31]. RCT: Gilling et al. compared HoLR to TURP in 120 men followed for 12 months [28]. Both treatments resulted in significant and comparable improvements in symptom score, quality of life and peak flow rate [28]. Operating time was significantly longer during HoLR, catheter time and hospital stay shorter after HoLR [28]. Perioperative morbidity was lower after HoLR. The same research group reported on similar findings of an RCT in men with bladder outflow obstruction and large prostates ( grams) [29]. HoLR can be performed even in men with large prostates, as demonstrated by Kuntz and Lehrich who randomised 120 men with prostates larger than 100 gram to HoLR or open prostatectomy [30]. Improvement of symptoms and flow rate were comparable in both groups. Surgical time was longer after HoLR, hospital stay, catheterisation time were significantly shorter after HoLR [30]. Blood transfusions were required in 13% after open prostatectomy as compared to 0% after HoLR. These data demonstrate that HoLR can be performed even in men with very large prostates usually requiring open prostatectomy [30]. Long-term follow-up data: Encouraging long-term data are available with similar outcomes as conventional TURP [27]. Guidelines: The EAU guidelines stated that HoLR is a promising new technique with outcomes in the same range as those of TURP [2]. According to the AUA guidelines HoLR is an option for patients seeking an alternative method of resection/enucleation in medical centres where the procedure is available [3]. 4. Ablative therapies 4.1. Transurethral vaporisation of the prostate (TUVP) Technique: By applying well-established electrosurgical principles, TUVP uses modified transurethral equipment, including a roller ball electrode with increased surface area and generators that deliver uninterrupted, high electrical energy (Fig. 1). This process achieves greater vaporisation of tissue. Thermal damage to surrounding structures, even at a 300 W setting, does not seem to be a major problem, as shown by interstitial thermometry and clinical experience. The urine inside the bladder can be heated to temperatures exceeding 45 8C unless continuous irrigation of the bladder is performed. The major disadvantage of TUVP is that the clinical efficacy of the electrode rapidly decreases as tissue

6 A. Ponholzer et al. / EAU Update Series 2 (2004) desiccates, i.e. with larger prostates. The total energy used during TUVP is 8 10-fold higher than that of conventional TURP. Furthermore, the electrode must be activated for substantially longer than during conventional TURP. RCT: Six RCTs comparing TUVP usually to TURP are available [32 37]. In these 6 RCTs, the symptom scores declined by a mean of 79% and the Q max increased by 101% 12 months after TUVP. The corresponding numbers 12 months after TURP were 75% and 123%, respectively [32 37]. The morbidity spectrum of both procedures was comparable, the risk of bleeding and of the TUR syndrome is lower after TUVP. These data of RCTs suggest that the clinical efficacy of TUVP seems to be comparable to conventional TURP at least for patients with small prostates. Long-term data: Hammadeh et al. recently reported on the 5-year outcome of a prospective RCT comparing TUVP to TURP [37]. The 5-year follow-up data showed a significant and maintained improvement of IPSS, Q max and post-void residual volume in both arms [37]. In each arm, 13% underwent a re-operation within 5 years (re-operation rate of 3%/year) [37]. Incidences of erectile dysfunction and retrograde ejaculation were comparable in both groups. The findings of this 5-year RCT demonstrate that TUVP is as effective as standard TURP in the treatment of moderate size BPH [37]. Guidelines: Not mentioned in the EAU guidelines as it is considered to be rather a modification of conventional TURP than an MIT [2]; the AUA guidelines state that long-term comparative trials are needed to determine if TUVP is superior to standard TURP [3]. 5. Other technologies 5.1. Balloon dilatation Technique: Balloon dilatation of the prostate (BDP) involves the insertion of a balloon on a catheter tip through the urethra and into the prostatic urethra [38,39]. The balloon is then inflated to stretch the urethra where narrowed by the prostate. Short-term studies in the late 1980s were promising, but longterm studies disappointing. RCT: Donatucci et al. randomised TURP (n ¼ 25) to BDP (n ¼ 26) [38]. Symptomatic improvement was significant and comparable in both groups after 12 months [38]. Post-void residual volume and maximum flow rate reached baseline values after 12 months [38]. Long-term follow-up data: Disappointing long-term follow-up data. Guidelines: Not recommended according to the AUA guidelines and not mentioned any more in the EAU guidelines [2,3]. This technique is considered obsolete for this indication Prostatic stents Guidelines: As prostatic stents are associated with significant complications, such an encrustation, infection and chronic pain, the AUA guidelines recommend their placement only in high-risk patients, especially in those with urinary retention [3]. Prostatic stents are not mentioned in the EAU guidelines (Fig. 1) [2]. 6. Recent developments Transurethral injection of absolute alcohol into the prostate results in a coagulative necrosis (chemoablation) (Fig. 1). Small, single-centre studies have reported encouraging data, although significant side effects such as bladder necrosis requiring surgical intervention have been reported as well [40]. A multicentre trial evaluating this technology in patients with BPH is currently underway. Guidelines: Due to its recent development, chemoablation is not mentioned in the EAU and AUA guidelines [2,3]. Using plasma energy in a saline environment, tissue vaporisation can be achieved with minimal thermal spread and enhanced haemostasis. This technique has the potential to increase safety by eliminating potential hyponatremia and TUR syndrome. An encouraging, single-centre study with a short-term experience in 40 patients has been published [41]. 85% of the patients were to return home on the day of surgery [41]. Guidelines: This technique is considered investigational according to the AUA guidelines and not mentioned in the EAU guidelines [2,3]. 7. Discussion During the past 15 years we have seen substantial developments in the field of MIT for BPH. First reports of virtually all techniques were enthusiastic suggesting that the end of conventional TURP has come. Many early techniques, such as hyperthermia, lowenergy TUMT, balloon dilatation and transurethral

7 30 A. Ponholzer et al. / EAU Update Series 2 (2004) Table 1 Overview on anaesthesia requirements, efficacy, durability, side effects, availability of RCT and EAU guideline recommendations of MIT Technique Anaesthesia requirements Efficacy Durability Side effects RCT EAU guidelines Hyperthermia Local Low Low Minimal n ¼ 2 Not recommended HIFU General Interm. Low Minimal n.a. Investigational WIT Local Interm. n.a. Minimal n.a. Investigational TUNA Local/iv-sedation Interm. Interm. Minimal n ¼ 2 Not recommended as a first-line treatment LE-TUMT Local Low Low Minimal n ¼ 3 Not recommended HE-TUMT Local/iv-sedation Interm. Interm. Minimal n ¼ 5 Recommended VLAP General High High Moderate n ¼ 8 Not recommended as first-line treatment; for high-risk patients ILC Local/iv-sedation general Interm. Interm. Moderate n ¼ 2 Not recommended as first-line treatment; for high-risk patients HoLR General High High Moderate n ¼ 3 Promising; same efficacy as TURP TUVP General High High Moderate n ¼ 6 Not mentioned Ballon dilatation Local/iv-sedation Low Low Minimal n ¼ 1 Not recommended Stents iv-sedation/general Interm. Interm. High n.a. Only for high-risk patients in retention Chemoablation Local/iv-sedation Interm. n.a. Moderate n.a. Investigational Interm.: Intermediate, n.a.:not available. laser-induced prostatectomy (TULIP) have largely been abandoned and are not recommended by the vast majority of BPH guidelines. When assessing the current role of MIT a number of parameters, such as the need for anaesthesia, intra- and postoperative complications, morbidity, short- and long-term outcome, durability and costs have to be considered (Table 1). One attracting aspect of MIT is the avoidance of anaesthesia thus being able to treat high-risk patients unfit for general anaesthesia or to be performed on a purely outpatient basis (Table 1). However, only transurethral heating techniques (TUMT and WIT) can be reliable performed under local anaesthesia. TUNA and ILC usually require some form of IV sedation. More invasive MIT, such as TUVP and various laser approaches require general anaesthesia, such as conventional TURP. Another driving force for the development of MIT is the avoidance of the two major TURP-related complications, namely bleeding and TURP syndrome (Table 1). In a large-scale series reported by Mebust on 3885 patients operated between 1978 and 1987, the transfusion rate was 2.5% [42]. Horninger et al. reported on a transfusion rate of 4.2% in 1211 consecutive patients treated between 1988 and 1991 [43]. In a recent review on 29 RCTs with a TUR arm, the transfusion rate was still as high as 8.6% [1]; a TURP syndrome has been reported in the range of 1 2% in most large-scale TURP studies. A major advantage of all MIT is that the risk of bleeding and of a TUR syndrome is minimal. In fact, these procedures can even be safely performed in patients with bleeding disorders or under warfarin therapy. In parallel, stress urinary incontinence, although rarely seen in contemporary TURP series, can be safely avoided. MITs, however, lead to a shift of the morbidity spectrum from the intraoperative phase (minimal risk of bleeding and TUR syndrome) to the postoperative phase. The major postoperative complication of any non-ablative procedure (TUNA, ILC, TUMT, non-contact VLAP, etc.) is a prolonged period of retention lasting for up to 6 weeks requiring tranusrethral or suprapubic catheterisation. Antiphlogistics, a 1 -blockade and temporal or biodegradable stents have been used to overcome this disadvantage. A further disadvantage of many MIT is the high degree of postoperative dysuria. This is particularly evident for MIT resulting in tissue necrosis, which is sloughed transurethrallly for the first postoperative weeks (e.g. VLAP) [44]. Schatzl et al. studied the degree of postoperative dysuria with a diary-type questionnaire following HIFU, TUNA, TUVP, non-contact VLAP and TURP [44]. This study has demonstrated a substantial degree of postoperative dysuria particularly following non-contact VLAP, e.g. a nocturia of 4 5 times was reported during the first 6 postoperative weeks [44]. In fact, it was this high degree of postoperative dysuria, which largely abandoned non-contact VLAP [44]. A major concern particularly for younger men requiring BPH surgery is the risk of sexual dysfunction following treatment. The long-standing controversy on erectile dysfunction after TURP was clarified by the VA Cooperative Study Group comparing TURP with watchful waiting [45]. After a mean follow-up of 2.8 years, the proportion of patients deteriorating of their sexual performance was identical in both arms, i.e. 19% after TURP and 21% after watchful waiting [45].

8 A. Ponholzer et al. / EAU Update Series 2 (2004) The incidence of retrograde ejaculation after TURP depends on the degree of bladder neck resection, in a recent meta-analysis this incidence was 65% [1]. Impairment of erectile function after MIT has never been observed. The incidence of retrograde ejaculation after MIT depends on the invasiveness of the procedure and if preservation of the bladder neck is obtained. Antegrade ejaculation is preserved in up to 70% following TUMT, TUNA, ILC and WIT. More invasive MIT, such as TUVP, VLAP or HoLR result in incidences of retrograde ejaculation comparable to TURP. TURP is considered to be a rather difficult surgical procedure requiring more than 100 cases to become familiar with this operation. The substantial decline in the number of TURPs during the past decade particularly in the USA and, to a less extent, in Europe, as a result of the introduction of effective medical therapy and MIT, led to problems in urological training programs. An attracting aspect of many MIT is the short learning curve. Procedures like TUMT, TUNA, ILC, VLAP and TUVP require few cases to achieve an adequate skill, particularly for urologists familiar with endoscopic procedures and TURP. Selectively HoLR has a longer learning curve and requires approximately 50 cases to become familiar with this technique. Regarding clinical efficacy, conventional TURP is still the gold standard. Although improvements of symptoms following MIT are generally in the range of TURP, changes of objective and urodynamic parameters are more profound after TURP. In general, there is a close correlation between the invasiveness of a MIT and its clinical efficacy. Procedures like TUMT, TUNA or ILC lead only to moderate improvements of Q max in the range of 2 6 ml/s and a 20 50% reduction of post-void residual volume (Table 1). More invasive procedures, such as TUVP and particularly HoLR lead to changes comparable as conventional TURP (Table 1). The definitive urodynamic impact of procedures designed to relieve BOO can only be assessed by pressure flow studies (pqs). In an extensive review, Bosch summarised the urodynamic effects of various treatment modalities for BPH [46]. The rank order of urodynamic efficacy as determined in this meta-analysis revealed that the most efficient therapy in relieving BOO was open prostatectomy, followed by TURP, VLAP, TUVP, TUIP, TUMT, TUNA and HIFU [46]. One of the crucial issues of any therapy of LUTS for BPH/BPE is the durability of the clinical response (Table 1). The rate of secondary intervention needed is the essential variable for evaluating the long-term efficacy of procedures aimed at relieving bladder outflow obstruction. In a large-scale, landmark study of patients undergoing TURP in Denmark (n ¼ 27; 911), England (n ¼ 2171) and Canada (n ¼ 8995) the reintervention after TURP was % within 12 months, % after 5 years and % at 8 years [47]. In a recent meta-analysis of 29 RCTs with a TURP arm, the rate of secondary intervention after TURP was 2.6% with a mean follow-up of 16 months [1]. The need for secondary intervention is substantially higher after MIT. Indeed, many of these procedures reach the 5 8 years re-intervention rate after TURP within the first 12 months [1]. Three years after low-energy TUMT, the failure rate was 29 52%, two years after transrectal HIFU, 20% of patients required TURP [1]. Following high-energy TUMT, 4 15% require re-intervention, similar percentages were reported following TUNA [1]. The re-treatment rate following TUVP and HoLR seems to be comparable to TURP [1]. A drawback of many MIT is fact that anatomical limitations hinder their general application, in particular regarding prostate volume and prostate shape. Large prostates, for instance, cannot be reliable treated by VLAP, HIFU and TUVP; patients with large median lobes are generally considered not good candidates for TUMT, TUNA and HIFU. HIFU cannot be performed in men with prostates with dense calcifications because of the possibility of tissue cavitation and with a large rectum to bladder neck distance over 40 mm. 8. Conclusions When assessing the current role of MIT for the treatment of LUTS due to BPO a number of parameters, such as the need for anaesthesia, intra- and postoperative complications, morbidity, short- and long-term outcome and costs (not discussed herein) have to be considered (Table 1). Many early MITs, such as balloon dilatation, hyperthermia and TULIP have been abandoned despite initial enthusiastic reports. If one defines an MIT based on the avoidance of anaesthesia, TUMT is currently the most attractive option with more than 100,000 patients treated worldwide during the past decade. The clinically most effective MITs are TUVP (particularly for small prostates) and HoLR. Both procedures, however, require general anaesthesia (such as conventional TURP) and can therefore also be considered as modifications of conventional TURP. BPH guidelines such as those of the EAU and AUA give clear recommendations in this evolving field [2,3]. Treatments not considered established by these and other guidelines should not be used outside the context of clinical trials [2,3].

9 32 A. Ponholzer et al. / EAU Update Series 2 (2004) References [1] Madersbacher S, Marberger M. Is TURP still justified? Br J Urol 1999;83: [2] de la Rosette J, Alivizatos G, Madersbacher S, Perachino M, Thomas D, Desgrandchamps F, et al. EAU guidelines on benign prostatic hyperplasia (BPH). Eur Urol 2001;40: [3] AUA Practice Guideline Committee. AUA guidelines on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol 2003;170: [4] Madersbacher S, Marberger M. High intensity focused ultrasound in urology. European Urology Update Series 1997;6: [5] Madersbacher S, Schatzl G, Djavan B, Stulnig T, Marberger M. The long-term outcome of transrectal high intensity focused ultrasound therapy for benign prostatic hyperplasia. Eur Urol 2000;37: [6] Muschter R, Schorsch I, Danielle L, Russel C, Timoney A, Yachia D, et al. Transurethral water-induced thermotherapy for the treatment of benign prostatic hyperplasia: a prospective multicenter clinical trial. J Urol 2000;164: [7] Bruskewitz R, Issa MM, Roehrborn CG, Naslund MJ, Perez-Marrero R, Shumaker BP, et al. A prospective, randomised 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia. J Urol 1998;159: [8] Cimentepe E, Unsal A, Saglam R. Randomized clinical trial comparing transurethral needle ablation with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: results at 18 months. J Endourol 2003;17: [9] Zlotta AR, Giannakopoulos X, Maehlum O, Ostrem T, Schulman CC. Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers. Eur Urol 2003;44: [10] Hindley RG, Mostafid AH, Brierly RD, Harrison NW, Thomas PJ, Fletcher MS. The 2-year symptomatic and urodynamic results of a prospective randomized trial of interstitial radiofrequency therapy vs transurethral resection of the prostate. BJU Int 2001;88: [11] Grava S, Laguna P, de la Rosette J. Thermotherapy and thermoablation for benign prostatic hyperplasia. Curr Opin Urol 2003;13:45 9. [12] Hallin A, Berlin T. Transurethral microwave thermotherapy for benign prostatic hyperplasia: clinical outcome after 4 years. J Urol 1998;159: [13] Dahlstrand C, Walden M, Geirsson G, Pettersson S. Transurethral microwave thermotherapy versus transurethral resection for symptomatic benign prostatic obstruction: a prospective randomized study with a 2-year follow-up. Br J Urol 1995;76: [14] Ahmed M, Bell T, Lawrence WT, Ward JP, Watson GM. Transurethral microwave thermotherapy (Prostatron version 2.5) compared with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: a randomized, controlled, parallel study. Br J Urol 1997;79: [15] D Ancona FC, Francisca EA, Witjes WP, Welling L, Debruyne FM, de la Rosette JJ. High energy thermotherapy versus transurethral resection in the treatment of benign prostatic hyperplasia: results of a prospective randomized study with 1 year of followup. J Urol 1997;158: [16] Wagrell L, Schelin S, Nordling J, Richthoff J, Magnusson B, Schain M, et al. Feedback microwave thermotherapy versus TURP for clinical BPH a randomized controlled multicenter study. Urology 2002;60: [17] Norby B, Nielsen HV, Frimodt-Moller PC. Transurethral interstitial laser coagulation of the prostate and transurethral microwave thermotherapy vs transurethral resection or incision of the prostate: results of a randomized, controlled study in patients with symptomatic benign prostatic hyperplasia. BJU Int 2002;90: [18] Anson K, Nawrocki J, Buckley J, Fowler C, Kirby R, Lawrence W, et al. A multicenter, randomized, prospective study of endoscopic laser ablation versus transurethral resection of the prostate. Urology 1995;46: [19] Cowles 3rd RS, Kabalin JN, Childs S, Lepor H, Dixon C, Stein B, et al. A prospective randomized comparison of transurethral resection to visual laser ablation of the prostate for the treatment of benign prostatic hyperplasia. Urology 1995;46: [20] Kabalin JN, Gill HS, Bite G, Wolfe V. Comparative study of laser versus electrocautery prostatic resection: 18-month followup with complex urodynamic assessment. J Urol 1995;153:94 7. [21] Sengor F, Kose O, Yucebas E, Beysel M, Erdogan K, Narter F. A comparative study of laser ablation and transurethral electroresection for benign prostatic hyperplasia: results of a 6-month follow-up. Br J Urol 1996;78: [22] Keoghane SR, Sullivan ME, Doll HA, Kourambas J, Cranston DW. Five-year data from the Oxford Laser Prostatectomy Trial. BJU Int 2000;86: [23] Gujral S, Abrams P, Donovan JL, Neal DE, Brookes ST, Chacko KN, et al. A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study. J Urol 2000;164: [24] Shingleton WB, Farabaugh P, May W. Three-year follow-up of laser prostatectomy versus transurethral resection of the prostate in men with benign prostatic hyperplasia. Urology 2002;60: [25] Planz B, Kalem T, Sprenger C, Deix T, Djavan B, Hanke P. A prospective randomized study of combined visual laser ablation and transurethral resection of the prostate versus transurethral prostatectomy alone. Urol Int 2003;71: [26] Kursh ED, Concepcion R, Chan S, Hudson P, Ratner M, Eyre R. Interstitial laser coagulation versus transurethral prostate resection for treating benign prostatic obstruction: a randomized trial with 2- year follow-up. Urology 2003;61: [27] Aho TF, Gilling PJ. Laser therapy for benign prostatic hyperplasia: a review of recent developments. Curr Opin Urol 2003;13: [28] Gilling PJ, Mackey M, Cresswell M, Kennett K, Kabalin JN, Fraundorfer MR. Holmium laser versus transurethral resection of the prostate: a randomized prospective trial with 1-year follow up. J Urol 1999;162: [29] Tan AH, Gilling PJ, Kennett KM, Frampton C, Westenberg AM, Fraundorfer MR. A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). J Urol 2003;170: [30] Kuntz RM, Lehrich K. Transurethral holmium laser enucleation versus transvesical open enucleation for prostate adenoma greater than 100 gm.: a randomised prospective trial of 120 patients. J Urol 2002;168: [31] Hochreiter WW, Thalmann GN, Burkhard FC, Studer UE. Holmium laser enucleation of the prostate combined with electrocautery resection: the mushroom technique. J Urol 2002;168: [32] van Melick HH, van Venrooij GE, Eckhardt MD, Boon TA. A randomized controlled trial comparing transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia: analysis of subjective changes, morbidity and mortality. J Urol 2003;169: [33] Kaplan SA, Laor E, Fatal M, Te AE. Transurethral resection of the prostate versus transurethral electrovaporization of the prostate: a blinded, prospective comparative study with 1-year followup. J Urol 1998;159: [34] Kupeli S, Baltaci S, Soygur T, Aytac S, Yilmaz E, Budak M. A prospective randomized study of transurethral resection of the prostate and transurethral vaporization of the prostate as a therapeutic alternative in the management of men with BPH. Eur Urol 1998;34:15 8. [35] Talic RF, El Tiraifi A, El Faqih SR, Hassan SH, Attassi RA, Abdel-Halim RE. Prospective randomized study of transurethral

10 A. Ponholzer et al. / EAU Update Series 2 (2004) vaporization resection of the prostate using the thick loop and standard transurethral prostatectomy. Urology 2000;55: [36] McAllister WJ, Karim O, Plail RO, Samra DR, Steggall MJ, Yang Q, et al. Transurethral electrovaporisation of the prostate: is it any better than conventional transurethral resection of the prostate? BJU Int 2003;91: [37] Hammadeh MY, Madaan S, Hines J, Philp T. 5-year outcome of a prospective randomized trial to compare transurethral electrovaporization of the prostate and standard transurethral resection. Urology 2003;61: [38] Donatucci CF, Berger N, Kreder KJ, Donohue RE, Raife MJ, Crawford ED. Randomized clinical trial comparing balloon dilatation to transurethral resection of prostate for benign prostatic hyperplasia. Urology 1993;42:42 9. [39] Saporta L, Aridogan IA, Erlich N, Yachia D. Objective and subjective comparison of transurethral resection, transurethral incision and balloon dilatation of the prostate. A prospective study. Eur Urol 1996;29: [40] Ditrolio J, Patel P, Watson RA, Irwin Jr RJ. Chemo-ablation of the prostate with dehydrated alcohol for the treatment of prostatic obstruction. J Urol 2002;167: [41] Eaton AC, Francis RN. The provision of transurethral prostatectomy on a day-case by using bipolar plasma kinetic technology. BJU Int 2002;89: [42] Mebust WK, Holtgrewe HL, Cockett ATK, Peters PCwriting committee. Transurethral prostatectomy: immediate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol 1989;141: [43] Horninger W, Unterlechner H, Strasser H, Bartsch G. Transurethral prostatectomy: mortality and morbidity. Prostate 1996;28: [44] Schatzl G, Madersbacher S, Lang T, Marberger M. The early postoperative morbidity of transurethral resection of the prostate and of 4 minimally invasive treatment alternatives. J Urol 1997;158: [45] Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM, Henderson WG for the Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med 1995;322: [46] Bosch JL. Urodynamic effects of various treatment modalities for benign prostatic hyperplasia. J Urol 1997;158: [47] Roos NP, Wennberg JE, Malenka DJ, Fisher ES, McPherson K, Andersen TF, et al. Mortality and reoperation after open and transurethral resection of the prostate for benign prostatic hyperplasia. N Engl J Med 1989;320: CME questions Please visit to answer these CME questions on-line. The CME credits will then be attributed automatically. 1. Which of the following statements regarding anaesthesia requirements during minimally invasive therapy for BPH is correct? A. All minimally invasive procedures can be performed under local anaesthesia. B. Holmium-laser enucleation and transurethral electrovaporisation require general anaesthesia, such as conventional TURP. C. Transurethral microwave thermotherapy and transurethral needle ablation usually require general anaesthesia. D. The avoidance of anaesthesia is the major advantage of visual laser ablation of the prostate. 2. Which of the following statements of the EAU BPH guidelines on minimally invasive procedures is correct? A. Transurethral and transrectal hyperthermia are established therapies for BPH. B. These guidelines make no statements on minimally invasive treatments. C. According to the EAU guidelines, high-energy TUMT is an accepted option for men with LUTS due to BPO. D. Stents are highly recommended treatments for men with a life expectancy of >10 years. 3. Which of the statements regarding intra- and postoperative morbidity of minimally invasive procedures is correct? A. The risk of bleeding and of a TURP syndrome following MIT is comparable to that of conventional TURP. B. Following high-energy transurethral microwave thermotherapy the vast majority of patients are able to void spontaneously within 48 hours. C. None of the minimally invasive procedures can be performed in patients with bleeding disorders. D. The major disadvantage of non-contact visual laser ablation of the prostate is the high degree of postoperative dysuria caused by tissue sloughing. 4. Which of the following statements regarding the efficacy of minimally invasive therapies for BPH is correct? A. Improvements of symptoms and urodynamic parameters are comparable following minimally invasive therapies and conventional TURP. B. The long-term outcome following high-energy microwave thermotherapy and transrectal highintensity focused ultrasound is similar to that of conventional TURP. C. There exists a rather close correlation between the invasiveness of a procedure and its clinical efficacy. D. The currently two most effective minimally invasive procedures are holmium-laser enucleation and balloon dilatation.