Minimally Invasive and Endoscopic Management of Benign Prostatic Hyperplasia

John M. Fitzpatrick, MCh, FRCSI, FC Urol (SA), FRCSGlas, FRCS













The prostate continues to be central to urologic practice in terms of the volume of cases that arise involving a disorder of that organ, be it benign, malignant, or inflammatory. Because of this, the amount of money available from grant-giving authorities for research into prostatic diseases is probably the highest for any research on the genitourinary tract, and so inevitably our interest in and understanding of the pathogenesis of problems relating to prostatic conditions have increased greatly. This has led to increasingly effective therapies for some prostatic abnormalities, but after the initial advances in the management of benign prostatic hyperplasia (BPH) of 10 to 12 years ago, how far have things moved forward? And, although groups of patients are continually being identified who would benefit from individual or combined medical treatments, can we say that the same has been happening in our development of minimally invasive therapies?


One thing that is certain is that in our investigation of medical therapy of BPH the identification of groups of patients who would best respond to different drugs has taken many large trials with long-term follow-up and careful statistical powering to demonstrate equivalence or a predefined difference. One always has the feeling that drug trials keep moving forward, leading to a greater understanding of the condition itself and of the ideal treatment for BPH. It can be said with some degree of confidence that the advent of medical management has reduced greatly the indications for and the number of patients undergoing transurethral resection of the prostate (TURP) and has also strongly influenced the wish of patients to have TURP, in that they would now prefer to try most other types of treatment before agreeing to undergo this procedure.


As the pharmacologic management of BPH was flourishing, many new minimally invasive therapies were being introduced. The huge success that greeted the development of technologic innovations in the management of renal calculous disease with percutaneous nephrolithotomy and extracorporeal shockwave lithotripsy prompted most of us to believe that the same could be achieved with BPH.


The yardstick against which the new minimally invasive therapies were measured was, of course, TURP. This was a very significant technologic innovation when it was introduced, and it went through a considerable amount of evolution before it reached the high levels of excellence that it has reached today. We know that it does not seem to produce as good results as the open prostatectomy, but it is not far behind. This statement is made without there having been a randomized trial between the two procedures, and comments on the safety and efficacy of one against the other are not evidence based. However, TURP can be viewed as a highly effective treatment with an acceptable complication rate, so much so that it is now accepted as the “gold standard,” that is, the standard against which other minimally invasive therapies must be measured and the standard that it is hoped they can achieve.


One of the slightly disappointing things is that although many of these therapies have been introduced, in spite of the fact that they were originally welcomed as a significant advance in the treatment of BPH, in the longer term they have not turned out to be so. In many cases, the conclusion that they were of value was based on a series of poorly constructed short-term trials in which intention-to-treat analysis of the results may not have been rigidly adhered to. However, the demise of some of the earlier technologies has led to strengthening and evolution of the newer ones, all of which has been beneficial for patients with BPH.


It should also be remembered why it is that the new minimally invasive techniques have been introduced. Ideally, they have been popularized and developed in the hope that they will have less complications than TURP, less requirement for anesthesia, and a shorter hospital stay and if possible will be less expensive. If the treatment is as effective as TURP, it should be ahead on one of these counts, and if it is not as efficacious, a rationale for its use should be devised, in addition to attempts at the identification of the patients most likely to benefit from it. Its exact therapeutic positioning in the management of BPH should be found.


The discussion presented here focuses on the current approach to the minimally invasive and endoscopic management of BPH. The literature has been critically and fairly reviewed, and the information outlined has relied heavily on evidence-based principles. When level I evidence is available, such as a meta-analysis or systematic literature review, the reader’s attention will be drawn to it. The purpose of all of this is to present the data so that readers will be able to make a valued judgment on the various treatment options, thus helping in their urologic practice.



Intraprostatic Stents


One of the earliest attempts to find less traumatic methods of treating symptomatic BPH was the introduction of either temporary or permanent intraprostatic stents, and, to a degree, they are still being used. They were first introduced as a method of treating certain cardiovascular conditions; and since the work of Dotter (1969), they have also been part of the treatment for peripheral vascular disease. They have since been used to treat stenosis of the coronary, femoral, and renal arteries (Maass et al, 1982; Dotter et al, 1983; Wright et al, 1985; Palmaz et al, 1987). Other types of obstruction have also been treated by the placement of stents: vena caval obstruction (Furui et al, 1990), bronchial obstruction (Mair et al, 1990), and tracheal stenosis (Skapshay et al, 1989). Even cervical stenosis (Luesley et al, 1990) and lacrimal duct obstruction (Hurwitz, 1989) have been treated in this manner. It is clear that stents have a role to play in treating obstruction in different parts of the body, but the exact role needs to be defined accurately. In the case of coronary artery disease, for example, a trial comparing stents with coronary artery bypass grafting is still awaited. In the case of the prostate, it took some time before it was realized that the role of stents was rather a limited one and that they would not replace TURP in every patient.


One of the few innovations that have occurred has been the introduction of a new temporary prostatic stent, which is based on a modification of the Foley catheter. This is described in detail later.


The idea of using stents for splinting the lobes of the prostate was derived from their original use in the cardiovascular system, where they are used to prevent arterial restenosis after angioplasty. Fabian (1980) first described the use of stents in urology when he suggested their usefulness in the treatment of outlet obstruction secondary to enlargement of the prostate. At some time after this the use of stents was advocated in the treatment of urethral strictures, and, subsequent to this, the use of prostatic stents became widespread, with the introduction of many different types: stents are now available in different lengths, diameters, materials, and designs.


As mentioned earlier, when stents were introduced as a treatment for symptomatic BPH, their exact role was uncertain and tended to be overstated as perhaps something that could be used in virtually every case. Eventually it became clear that their major role was likely to be found in the management of patients who were unfit for surgery, in either the short or the long term, in which the alternative would have been months or, indeed, a lifetime of indwelling urethral catheterization.


Along with these changes in the indications for the use of stents have emerged two basic types of stent: that which is put in for a short time and can be removed with ease and that which is placed as a permanent type of treatment and can be removed only with much greater difficulty.



Temporary Stents


Temporary stents are tubular devices that are made of either a nonabsorbable or a biodegradable material. They remain in the prostatic urethra for a limited period of time; they neither become covered by the urethral epithelium nor become incorporated into the urethral wall. The nonabsorbable stents need to be removed every 6 to 36 months, depending on which type of material is used. They can usually be removed, and, if necessary, replaced, without difficulty with the patient under topical anesthesia with sedation.


Temporary stents are designed for short-term use, to relieve bladder outlet obstruction (BOO), and to act as an alternative to an indwelling urethral or suprapubic catheter in high-risk patients considered unfit for surgery. In such patients these temporary stents permit normal micturition with an acceptable side effect profile. Success rates have been reported in the range of 50% to 90%. They are easy to reposition or replace, but catheterization or cystoscopy cannot be performed while the stent is in place. Complications such as encrustation, migration, breakage, stress incontinence, and bacteriuria have been reported in varying degrees of frequency.



Spiral Stents



First-Generation Stents


The Urospiral (Porges) and the Prosta Kath (Pharma-Plast) are examples of spiral stents. The former is made of 21-Fr stainless steel and varies between 40 and 80 mm in length. The latter is also made of 21-Fr stainless steel but is gold plated in an attempt to prevent encrustation. It varies in length between 35 and 95 mm. Neither stent should remain in the prostatic urethra for longer than 12 months.


A spiral stent should be inserted with a 21-Fr panendoscope using either a 30-degree or a 0-degree lens under direct vision and with the aid of a grasping forceps. It may also be inserted over a catheter guide under ultrasound visualization (Nordling et al, 1989).


In the original series reported by Nordling and colleagues (1989), the Prosta Kath was inserted under topical anesthesia in 45 patients with acute or chronic retention. Ultrasonography was used in 35 patients and endoscopy in 6 to facilitate stent placement. Retention was relieved in 41 of the 45 patients, leading the authors to advocate its use in high-risk patients.


Ozgur and coworkers (1993) reported re-establishment of voiding with the Urospiral with good results after 4 months of follow-up in 31 patients who were unfit for surgery. The Urospiral was also used in 10 patients with advanced prostate cancer (Anson et al, 1993). All had retention or severe obstruction. The patients were started on antiandrogens after stent insertion. The stent was removed 3 months later, and all patients were reported as voiding satisfactorily, although one patient subsequently required a limited TURP. In another report, 18 high-risk patients with BPH had a Urospiral inserted (Karaoglau et al, 1992). All voided without difficulty and with complete bladder emptying. However, the complications were rather high: hematuria in 2, migration in 1, and infection in 8.


In 87 patients declared unfit for TURP, Thomas and colleagues (1993) reported an experience extending over 4 years using the Prosta Kath. Sixty-four patients presented with acute urinary retention, and, after treatment, 57 voided successfully whereas 7 failed to void. A further 14 patients presented with chronic urinary retention; 5 of these voided satisfactorily, but 9 required alternative therapy. Complications included hematuria with clot retention (5%), stent migration (15%), recurrent urinary tract infections (10%), and encrustation (4%). These findings of relatively high complications are also reported by other authors (Nordling et al, 1989; Harrison and De Souza, 1990). Braf and coworkers (1996) observed 55 men for between 12 and 16 months, 32 of whom were treated with the Prosta Kath and 23 with the Urospiral. Ten patients failed in the Prosta Kath group, and 8 patients failed in the Urospiral group. Complications in both groups include encrustation, urinary tract infection, migration, stricture formation, and failure to void. In the largest number of patients reported from one center Nordling and associates reported on the use of the Prosta Kath in 318 patients. They divided the complications into none, moderate, and severe. In the patients who were described as having severe complications, stress or urgency incontinence occurred in 63, emptying problems in 8, and frequency or nocturia (more than three times per night) or both in 57.



Second-Generation Stents


Other spiral stents have been developed as second-generation models in an attempt to overcome the problems of the first-generation stents just described while maintaining the efficacy and ease of insertion. These are the Memokath and the Prosta Coil.


The Memokath (Engineers and Doctors A/S, Copenhagen, Denmark) is made of nitinol, a nickel-titanium alloy, which has the property of shape memory. It is malleable and heat expandable at a temperature of 45° C to 50° C. Like other temporary stents, it is easy to insert and maintains its expanded position in the prostatic urethra. With the earlier model of the Memokath, epithelial hyperplasia at the apex of the prostate was reported in some cases, but modifications have since been made. The later model ensured close contact of the wires even in the expanded position, thus reducing the possibility of hyperplastic growth of the urethral epithelium through the gaps in the expanded spiral. The Memokath is soft and malleable when cooled, returning to its original shape when heated to the preceding temperatures. Of 22-Fr caliber, it has a length of 35 to 95 mm. It permits the passage of a flexible cystoscope and may be left in place for up to 36 months.


The Prosta Coil is a self-expanding and self-retaining stent made of a nickel-titanium alloy (Instent, Minneapolis, MN). It is inserted by being mounted on a 17-Fr delivery catheter under fluoroscopy; once released from the mounting it takes the form of a wave-shaped tube whose diameter varies from 24 to 30 Fr. Its length is from 40 to 80 mm, and it can be left in position for up to 36 months.


The Memokath was reported as being used in 30 patients who were unfit for surgery or who refused it; the success rate was 80%. Normal voiding is described as having occurred in all patients. The peak urinary flow rate (PFR, also Qmax) reached a mean of 16 mL/sec immediately after insertion (Poulsen et al, 1993). However, there was a wide range of PFRs, from 4 to 25 mL/sec. Unfortunately, 3 patients later developed urinary retention at 5 days, 2.5 months, and 5 months, respectively, after insertion. Two more stents needed to be removed because of hyperplastic growth of the epithelium. A total of 24 stents were still in place at 3 months. Nordling (1996) updated these authors’ experience after inserting 64 of the modified Memokath stents. Similar successful voiding was reported. The complications that patients described as severe were few, with urgency incontinence being the most common (10 patients). However, moderate symptoms were relatively more common.


Results are available from a long-term study conducted in the United Kingdom. The Memokath was inserted in men who were either permanently or temporarily unfit for TURP, in most cases because of severe respiratory or cardiovascular disease. In this study, 211 men had 217 stents inserted over an 8-year period. In the same time frame, 1511 TURPs were performed. The mean age of patients having stents was 80.2 years, and in the TURP group it was 70.2 years. The patients who had stents fitted experienced an improvement in the mean International Prostate Symptom Score (IPSS) from 20.3 to 8.2 in just 3 months, with results being maintained for 7 years. However, these results must be viewed in the light of the fact that 38% died with stents in place, 34% remain alive with their stents, and 23% had stent removal because of failure. Migration occurred in 13%, and 16% required repositioning. This study suggests that long-term success can be achievable using the Memokath but that failure can also be anticipated in a significant minority (Perry et al, 2002).


The Prosta Coil has been used in a small series of patients with short follow-up (Yachia et al, 1994). The mean follow-up was 14 months, with a range of 2 to 28 months. There were initial irritative urinary symptoms that were reported as having disappeared within 1 month. The mean PFR at the most recent follow-up was 21.3 mL/sec (with a range of 15 to 36 mL/sec) and the mean IPSS was 9 (with a range of 6 to 12).


Thus spiral stents were among the earliest type of temporary stents to be introduced, and they have developed to a large degree from the original designs. New models have reduced such complications as encrustation and urothelial hyperplasia, but stress incontinence and urgency incontinence still occur, as does displacement of the stent. However, they are easy to insert and do not require general anesthesia. Although the follow-up is relatively short term, in most of the reported series, good success rates are reported. The place of spiral stents is clearly that of a nontraumatic therapy for urinary retention in patients unfit for surgery, and they have a reasonable chance of a successful outcome.


It is hard to predict whether further design changes will take place. The earlier type of spiral stents had the advantage of being less expensive. The newer models are made of compounds aimed to reduce complications or prevent stent migration but are all more expensive than the earlier models. With a limited market and with a restricted acceptability, further developments in this type of stent are unlikely.



Polyurethane Stents


Polyurethane stents are also known as intraurethral catheters. There are three types: the intraurethral catheter (Angiomed, Germany), the Barnes stent (CR Bard, Covington, GA), and the trestle stent (Microvasive, Boston Scientific, Natick, MA).



Intraurethral Catheter


The intraurethral catheter, the first to be introduced, was reported initially by Nissenkorn (1991). It is made of a type of polyurethane known as Puroflex and has a fixed 16-Fr caliber. Its length varies from 40 to 60 mm, and it can be left in place for up to 6 months. It has a double device at its proximal end shaped like the head of a de Pezzer or Malecot catheter. It has a nylon string at its distal end and a flared split end proximally, which sits in the bladder. It is inserted under topical anesthesia using a 22-Fr cystoscope. The nylon string is cut after placement, and any positional adjustment required can be performed by the use of a grasping forceps. Eighty-five devices were inserted into 73 patients, and, of these, 60 patients had an indwelling catheter for 1 week to 3 years before insertion. Nissenkorn (1991) described a successful outcome in 63 patients who believed that their quality of life was considerably better than it had been when they had an indwelling catheter. He therefore believed that this was suitable for use in such patients, with a high likelihood of success.


A later study reported the use of the Nissenkorn intraurethral catheter in 43 patients (Sassine and Schulman, 1994). Once again, the patients treated had developed urinary retention and were unfit for surgery but also had a short life expectancy. Thirty-six of the 43 patients were able to void satisfactorily after stent insertion. The intraurethral catheter should not be inserted in the presence of bladder stones or anything else likely to block or have a ball-valve effect on the device.


One of the potential uses of temporary prostatic stents is as an expedient to overcome the early retentive effects of heat treatment to the prostate. Clearly, an objection to this might be that such a therapeutic strategy effectively doubles the cost of the treatment and so makes it less attractive. However, it is an attractive way of overcoming an early complication of heat treatment, which might have been seen by some as a significant limitation of heat treatment. The Barnes stent and the trestle stent may have such an application.




Trestle Stent


The trestle stent or prostatic bridge catheter has been described and consists of two tubes and an interconnecting thread. The tube that lies in the prostate has a 22-Fr diameter and has a 30-degree angulation. The length is 75 mm, and it has a smooth tip: It is to be used in prostates with a volume of less than 80 mL. The connecting thread is 25 mm, which passes through the distal sphincteric mechanism. The second tube lies in the bulbar urethra and is 35 mm long. It is inserted with the patient under topical anesthesia using a delivery system comprising a positioning stylet, an inflatable balloon with injection cannula, and an outer pusher tube. The technique is described in detail by Djavan and colleagues (1999).


In a report from Devonec and Dahlstrand (1998) the results of its use in 52 patients after high-energy transurethral microwave therapy (TUMT) were described. Tolerance was good in 32 patients, acceptable in 13, and poor in 6. Retrograde ejaculation occurred in eight. PFRs reached 14.6 mL/sec on the day of removal of the device. The device was left in place for 1 month, but the improvement in PFR was maintained at 1 year. Djavan and colleagues (1999) also described its use in 54 patients who had received high-energy TUMT. The device was left in place for up to 1 month, and it was found that the incidence of post-treatment retention was prevented, with concurrent early but significantly improved symptom scores and PFRs. Toleration was high, with 48 of 54 devices remaining in place for 1 month. Early removal was required because of urinary retention in 3 and migration in 3.


The intraurethral catheter or its more recent variations are being used in a rather different context than the spiral stents. They have been used successfully, albeit in a small number of nonrandomized short-term studies, with few problems related to tolerance. A further cost-efficacy evaluation is required, in addition to larger multicenter randomized controlled comparative trials.




Biodegradable Stents


The concept of stents that can be put in place after a procedure that has a high incidence of secondary and temporary obstruction has been mentioned earlier in the context of stents being inserted after laser or high-energy TUMT. These stents are removed some weeks later. With the biodegradable stent the concept is brought one step further; the stents do not need to be removed, and eventually they disappear by biodegrading. This interesting idea was first introduced in urology when Kemppainen and colleagues (1993) used a biodegradable stent in rabbits after urethrotomy. The idea has now been extended to the ureter (Schlick and Planz, 1998; Lumiaho et al, 1999; Clayman, 2000), after endoscopic urethroplasty (Oosterlinck and Talja, 2000), and in coronary artery disease (Tamai et al, 2000).


Further experimental studies have shown that biodegradable stents can potentially be used as a bridge across the prostate after minimally invasive procedures, without the necessity of having to remove them later (Petas et al, 1997a, 1998; Laaksovirta et al, 2002; Vaajanen et al, 2003).


In addition, clinical studies have been performed that examine the use of biodegradable stents after various procedures (Talja et al, 1995; Dahlstrand et al, 1997; Petas et al, 1997b). The benefit is that these stents prevent the development of obstruction that can occur after laser procedures; however, the use of the second procedure in association with, for example, laser prostatectomy takes away a great deal from the value of the first procedure, not least in terms of cost-effectiveness. There are three types of biodegradable stents.


A randomized study (Petas et al, 1997b) compared self-reinforced polyglycolic acid biodegradable spiral stents (group 1), no device (group 2), or an indwelling catheter (group 3) after visual laser ablation of the prostate. The procedure was performed on 72 men, and 27 were in group 1, 23 in group 2, and 22 in group 3. Voiding began at a median of 1 day in group 1 and a median of 6 days in group 2; the indwelling catheter was required for an average of 6.5 days in group 3, and voiding commenced a median of 6 days after this. The authors found, as they had in previous in-vitro studies, that the stent degraded into small fragments of polymer debris that were passed out in the urine. They commented that voiding became more obstructed at 3 to 4 weeks postoperatively, presumably from degradation and sloughing of the stent, but they found that this was only a transient effect.


In another study, Dahlstrand and colleagues (1997) evaluated the same polyglycolic acid stent after high-energy TUMT with the Prostasoft 2.5. They compared the use of the stent in 15 patients against a further 15 patients in whom a standard 16-Fr urethral catheter was inserted. The mean duration of catheterization was 14.1 days, with a standard deviation of 4.1 days; this was obviously prevented by the stent, which did not cause problems, even when it was degrading.


In a rather innovative way, Knutson and colleagues (2003) described the use of a biodegradable polyglycolic acid stent to assess the risk of post-TURP incontinence in patients with combined BOO and overactive bladder. In 37 patients with severe overactive bladder and moderate to severe BOO this biodegradable stent was inserted into the prostatic urethra; 25 noticed either no leakage or minor leakage and 19 have had TURP with good results. Twelve of the 37 had a major problem with incontinence after the insertion of the stent. There was a small complication rate related to stent insertion.


These stents are definitely of interest for the future, but their exact place in the treatment of BPH needs to be established, with larger and longer-term studies. In addition, the problem related to the overall cost must be defined accurately; otherwise, the value of the primary procedure will be questioned.



Permanent Stents


With permanent stenting of the prostate, the urologist is attempting to treat definitively and permanently patients who present with symptomatic BPH. To be of proven value this type of treatment, like any other, must be shown to be at least comparable to TURP. The initial enthusiasm for permanent stents has been replaced by relative silence in the literature at present. Permanent stents were initially introduced as treatment for recurrent urethral strictures and were subsequently used in patients with lower urinary tract symptoms (LUTS). In urologic terms, permanent stents are being used preferentially for the treatment of detrusor-sphincter dyssynergia (Chancellor et al, 1999; Chartier-Kastler et al, 2000; Gajewski et al, 2000), postbrachytherapy BOO (Konety et al, 2000), anastomotic strictures and urinary incontinence after radical prostatectomy (Meulen et al, 1991), and complex urethral strictures (Tillem et al, 1997). There have been no reports in the recent literature that relate to the long-term follow-up of the patients originally treated with permanent stents, and there has been no indication of new interest in their use.



UroLume


The UroLume endourethral prosthesis (American Medical Systems, Minnetonka, MN) is a woven tubular mesh that maintains its position in the urethra by outward external pressure, thus maintaining the patency of the prostatic urethra. The original 42-Fr device was made of metal superalloy and varied in length from 1.5 to 4.0 cm. It is inserted with a special 21-Fr deployment tool using a 0-degree panendoscope. Gradually, epithelialization occurs, ideally in a smooth manner, covering the individual wires of the mesh. The stent can be removed by securing about 5 mm of the distal aspect in the jaws of a grasping forceps and then pulling the distal end inside a resectoscope sheath to minimize any possibility of urethral trauma while removing it.


The original stent tended to shorten while it expanded outward, leading to its replacement by a stent less likely to do so. However, this stent tended to migrate more easily, and a further modification was required. In addition to these changes the delivery tool was modified, leading to the present, more satisfactory model.


Chapple and colleagues (1990) reported on the initial experience with the UroLume. Twelve patients who were considered to be a poor risk for surgery presented with LUTS; 9 of the 12 patients presented with urinary retention. The results were encouraging, with 11 of 12 voiding satisfactorily for a mean follow-up of 8.2 months. The mean PFR after the procedure was 13.6 mL/sec. Further encouragement came from the low complication rate, consisting mainly of short-term irritative voiding symptoms, with only 1 of the 12 being dissatisfied because of severe urgency and frequency (the patient was subsequently found to have detrusor instability). A further study in a similar group of unfit patients was performed by McLoughlin and colleagues (1990). All 19 patients in their study group presented in urinary retention, and all voided satisfactorily after the stent was inserted under local anesthesia.


In a larger, multicenter open trial from the United States, Oesterling and colleagues (1994) reported on 126 men who presented either with moderate or severe LUTS (95 men) or with urinary retention (31 men). There were strict inclusion and exclusion criteria in the trial design, but fitness for surgery was not among them. In the nonretention group, 80 of 95 were evaluable at 12 months and 52 at 24 months; the Madsen symptom score decreased from 14.0 to 5.9 and 5.4, respectively. In the retention group, 24 of the 31 patients evaluable at 12 months had a mean symptom score of 6.1. In the nonretention group, the PFR increased from 9.1 to 13.0 and 13.1 mL/sec, respectively, with the retention group having a mean PFR of 11.7 mL/sec at 12 months. Difficulties with insertion were experienced in 16% of cases; irritative voiding symptoms occurred in 10%.


Guazzoni and coworkers (1994) described a European study using the modified UroLume stent (the so-called less shortening variety described earlier). Once again, the strict inclusion and exclusion criteria did not refer to fitness for surgery, and at this time the stent was being presented as a proposed therapy for prostatic obstruction, not necessarily only for unfit patients. In this multicenter study, 135 healthy patients (91 with LUTS, 44 with urinary retention) were treated. In the nonretention group, 74 of 91 patients were evaluable at 12 months. The mean Madsen-Iversen symptom score had decreased from 14.1 to 6.4, but the tight standard deviations of the mean observed in the U.S. study (0.4) were not seen in this study (5.1); the PFR improved from 9.3 to 15.7 mL/sec at 12 months (with a very wide standard deviation of 6.5, unlike that in the U.S. study). In the retention group, 34 of 44 were evaluable at 12 months; the mean symptom score was 4.5 and the mean PFR was 13.1 mL/sec. The complications were well described but were found to be significant in the long term.


In a British study (Bajoria et al, 1995), 44 men fit for TURP accepted as an alternative a second-generation UroLume stent. The stent was inserted in 44 patients, who either were in urinary retention or had urodynamically proven outflow obstruction. The results achieved were similar to those reported by Guazzoni and colleagues (1994), but there was also a relatively high complication rate. Both sets of authors noted epithelial hyperplasia and migration of the stent in addition to irritative urinary symptoms and painful ejaculation. The second-generation less shortening stent was not recommended for general use, and a third-generation stent was then produced. However, Bajoria and colleagues (1995) strongly suggested that permanent stents should still be considered as being under evaluation rather than for general use.


In a multicenter study of 96 men who were unfit for prostatic surgery, 73 presented in acute urinary retention and 11 in chronic retention. All but 6 were able to void immediately after stent insertion; 2 required a second stent, and 4 required a period of suprapubic catheter drainage. At 12 months, the PFR was 15 mL/sec in the retention group and 18.1 in the nonretention group. Severe irritative symptoms were seen in the majority of patients for up to 3 months, and encrustation was encountered in 15 of 27 patients who underwent cystoscopy (Williams et al, 1993).


The results of a long-term analysis of the UroLume Wallstent have been published by Masood and coworkers (2004). The stent was inserted in 62 patients with moderate or severe LUTS secondary to BPH. The 5- and 12-year follow-up was completed by 22 and 11 patients, respectively. Death occurred in 21 patients (34%), and the stent was removed in 29 patients (47%), the vast majority of these removals occurring in the first 2 years. The authors concluded that this is a safe treatment but that cases must be carefully selected and that it should be performed only by experienced hands.


The use of the UroLume stent can be seen to have some application in patients with prostatic obstruction, particularly if they are unfit. However, interest in this type of stent seems to have waned somewhat because of the use of other types of less invasive treatments, which appear more satisfactory to patient and urologist alike.



Memotherm


The Memotherm (Angiomed, Germany) is a stent of nickel-titanium alloy that is expandable to 42 Fr with heat. When it is cooled, it can easily be compressed and distorted, but when warmed to body temperature it expands to a flexible cylinder and does not shorten. It is made from a woven single wire, which makes it easy to remove; traction unravels the wire. It is manufactured in lengths varying between 1.5 and 8.0 cm and is available in a prepacked sterile delivery service. It is inserted under direct vision with a 0-degree telescope.


Williams and White (1995) reported on 48 men with LUTS and urodynamic findings suggestive of bladder outflow obstruction. The results were disappointing. Only 37 patients were able to void immediately after stent insertion, the others requiring a suprapubic catheter for up to 8 weeks. Symptomatic improvement occurred in many, but complications, including stent migration, were relatively high. Thirteen of the 48 patients required removal of their stents. These authors suggested that the results were not appropriate to encourage marketing of the device.


Gesenberg and Sintermann (1998) used the Memotherm in 123 patients considered to be at high risk for prostatic surgery; 46 of these presented in urinary retention. Of the 123 patients, only 52 were evaluable at 12 months. The mean PFR increased from 7.4 to 13.0 mL/sec (with a standard deviation of 6.2), and the IPSS improved from 24.0 to 8.8 (SD 6.2). The authors noted a considerable improvement in quality of life. However, the complication rate was relatively high, with recurrent infections and urgency symptoms in 56%, urothelial hyperplasia in 34%, and urethral stricture in 10%. There was a high number of re-treatments, and the authors suggested that there may be an additional role for medical treatment in some of these patients.


These results have not appeared to be convincing large numbers of urologists to use these stents on patients with symptomatic BPH, but modifications may occur. Heat-expandable stents are widely used in cardiovascular conditions and in biliary stenosis.



Other Permanent Stents


The ASI stent (Advanced Surgical Instruments) was evaluated in several centers (Kirby et al, 1992; Kaplan et al, 1995). It was introduced on a balloon, which was then inflated, thus expanding the stent. The early results suggested an improvement in symptom score (44%) and PFR (22%), but complications also occurred that made it less attractive for general use. It has since been withdrawn from production.


The Ultraflex stent (Boston Scientific, Natick, MA) is made of nickel-titanium alloy that also has a capacity to expand to a caliber of 42 French when exposed to body heat. It is available in lengths varying from 2 to 6 cm. There have been reports of its use in patients with prostatic obstruction, but it has been studied in a group of patients with detrusor-sphincter dyssynergia (Chartier-Kastler et al, 2000), and the incidence of epithelial hyperplasia and migration was encouragingly low.




Transurethral Needle Ablation of the Prostate


Heat treatment of whatever kind to the prostate is intended to reduce outflow resistance and the volume of the obstruction by increasing the temperature within the prostate and inducing necrosis of prostatic tissue. The aim is to increase prostatic temperature to in excess of 60° C. Transurethral needle ablation of the prostate (TUNA) uses low-level radiofrequency (RF) energy that is delivered by needles into the prostate and that produces localized necrotic lesions in the hyperplastic tissue. It has previously been used to ablate cardiac nerve bundles in the Wolff-Parkinson-White syndrome (Calkins et al, 1992) and to destroy malignant tissue (Rossi et al, 1995; Zlotta et al, 1995). It has also been used to treat chronic cervical zygapophyseal joint pain (Lord et al, 1996). The advantage of TUNA is that it can be delivered under topical anesthesia to patients with symptomatic BPH, causing very precise and reproducible lesions within the prostate.



Delivery of Radiofrequency Energy


The TUNA system (Medtronic, Inc, Minneapolis, MN) consists of a special catheter attached to a generator. At the end of the catheter are two adjustable needles that are withdrawn into two adjustable shields made from Teflon. The needles are advanced into the prostatic tissue and can be placed accurately into the required position.


The generator produces a monopolar RF signal of 490 kHz, which allows excellent penetration and uniform tissue distribution. The patient has a grounding pad placed over the sacrum, and the current passes toward this through the prostatic tissue. In other words, tissue heating is created because of tissue resistance to the current as it flows from the active to the return electrode. The active electrode has a small surface area, with the RF current being concentrated in an area immediately surrounding it. The return electrode is large, and so the diffusion of the RF current is greater. This arrangement allows heat to be concentrated near the active electrode early, thus accurately controlling the tissue effect. The size of the lesion caused by RF relates to the position and depth of insertion of the electrode as well as the power used and the duration of the treatment.


RF produces molecular or ionic agitation with collision of particles that relates to the frequency of the energy, and this results in a central hot core inside the prostate and away from the urethra (Schulman et al, 1993). The limited distance dissipation reinforces the safety of the procedure because RF can be applied to tissue only by direct contact, with heat being generated proportional to one over the fourth power of the radius. If the power generated is too high, the prostate rapidly desiccates with a rise in tissue impedance, preventing the desired heating effect. Therefore the appropriate energy level required to produce the localized necrotic lesion must be found, preventing the increase in tissue impedance resulting in prostatic charring around the needle caused by excessive generation of energy (Schulman et al, 1993). Interestingly, heat is lost by convection, and so increased vascularity can have an effect on the degree of localization of the lesion. RF is very much affected by blood flow and has almost no effect on vessels larger than 2 to 3 mm in diameter (Organ, 1976).


There is a difference in the method of tissue heating brought about by RF and, for example, microwave application. Microwaves treat a broad area and can penetrate tissue more deeply than RF. The central temperature is therefore lower than with RF to maintain safe heat levels at the treatment rim. Therefore treatment with microwaves takes longer than RF to produce coagulative necrosis. RF, however, has a much hotter central area with a very quick decline in temperature as the distance increases from the treatment needle. This results in faster generation of the necrotic lesion but of a smaller area (Perlmutter et al, 1993).



Experimental Studies


In a series of preliminary studies on animals and ex-vivo human prostates it has been shown that the TUNA system can create 1-cm necrotic lesions without difficulty in the prostate with no damage to rectum, bladder base, or distal prostatic urethra (Goldwasser et al, 1993; Ramon et al, 1993). Other studies showed that the lesions are accurate with sharp delineation from the untreated areas (Schulman et al, 1993). These authors also showed that the lesion appeared first as a hemorrhagic lesion along the needle path, with slight discoloration in the surrounding area. Necrosis was maximal at 7 days, with fibrosis having developed by 15 days.


In an elegant neurohistochemical study, Zlotta and colleagues (1997) removed prostates from patients scheduled for prostatectomy 1 to 46 days after TUNA. Immunohistochemistry was used with anti–S-100 protein and neuron-specific enolase for nerve staining and anti–prostate-specific antigen and antidesmin for glandular and muscle cells. They showed that the maximal lesion size ranged from 10 × 7 to 20 × 10 mm2 and that there was destruction of all tissue components. The lesions were accurately positioned 0.3 to 1.0 cm from the urethra, which remained undamaged. In the treated area there was an absence of staining for prostate-specific antigen, smooth muscle actin, and α-adrenergic neural tissue. Even in specimens removed 24 hours after TUNA, no positively staining nerve cells were seen in the treated areas.


It has also been shown (Issa et al, 1996) that there may be sequential damage to different types of nerve endings. Nitric oxide synthase receptors were found to be most vulnerable to thermal damage, which occurred earliest, with damage to the α-adrenergic receptors maximal at 1 to 2 weeks.


The temperatures achieved in the largest area have been studied by Rasor and coworkers (1993) using an infrared temperature monitor in an ex-vivo animal model. They showed that the central core of the lesion around the tip of the lesion reached 90° to 100° C. Treatment times of 5 to 7 minutes were required to produce coagulation necrosis in the treatment zone. Dosimetry studies have shown that the temperatures at the edge of the zone were 50° C.



Instruments


The generator produces low-level monopolar RF waves of about 490 kHz, which produce temperatures of about 100° C in the target area. The RF generator is connected to the TUNA catheter, which has changed somewhat in design since it was first manufactured.


The TUNA catheter is, in fact, a specifically designed endoscopic instrument. This has evolved from what was a device through which a panendoscope lens could be inserted. A number of other changes have also been made. The most up-to-date version of the TUNA catheter is called the Pro Vu system, and part of this device is reusable, unlike previous models (Fig. 93–2; see also Fig. 93–1). The new system also contains a markedly improved optical system. Previously, the needles were introduced either blindly or under transrectal ultrasound (TRUS) guidance, which had the advantage in the latter case of seeing how close to the surrounding tissues the needles lay. However, an adequate visualization of the needle entering the prostate tissue gives the urologist a better idea of the treatment area. The final change concerns the angle between the catheter and the needles, which is at present not fixed. This means that a high bladder neck that is hypertrophied or a genuine median lobe enlargement can now be treated easily by this technique.



The configuration of the needles within their protective sheath ensures that the treatment area is deep inside the prostatic lobes, and this ensures that the prostatic urethra is spared. Because there is a limited number of nerve endings in the prostatic glandular tissue and because the higher concentration of nerve endings immediately underlying the urethral epithelium remains undisturbed, topical anesthesia can be used with the patient experiencing only moderate discomfort. In addition, postprocedural irritative urinary symptoms are kept to a minimum.



Treatment


The patient is placed in the lithotomy position and topical anesthesia with 2% intraurethral lidocaine (Xylocaine) is achieved. The best result is attained by applying a penile clamp for 10 minutes and by giving intravenous sedation if required. There is a variation from institution to institution as to the optimum form of anesthesia; for many, what is described previously is satisfactory, but some prefer spinal or even general anesthesia, particularly for their initial experience with the technique. In other cases, a local prostatic block, either transperineally or transrectally, may be the method of choice.


With the new modifications the TUNA catheter is advanced under vision with the 0-degree fiberoptic telescope, which also allows the urologist to see the needles being advanced accurately into the prostate. The exact position within the prostate of the needle tip can be visualized by TRUS. Preprocedural assessment of the size of the prostate by this method allows calculation of the length of deployment of the needle within the prostate; this can also be done at the beginning of the procedure, as described earlier, with the ultrasound showing the exact position of the needle tip. It is important to remember that the thermal lesion may extend for up to 5 to 6 mm beyond the position of needle deployment with lesions measuring up to 20 × 10 mm. When the position is deemed satisfactory, the Teflon shield on the proximal part of the needle is advanced to protect the urethral epithelium and the underlying tissue. Therefore the tip of the needle should not lie within 5 to 6 mm of the outer rim of the prostate, and the urethra is protected by the shields that extend from 5 to 6 mm from the TUNA catheter itself.


The number of lesions depends on the size of the prostate, but because there are two needles each time power is switched on in the generator two lesions are produced. It is usually advised that one pair of lesions should be used to treat 20 g of prostate tissue; it can also be expressed in terms of length, with one pair of lesions, or treatment plane, being used for less than 3 cm of prostatic urethral length, two planes for 3 to 4 cm, and one extra plane of treatment for every extra centimeter of urethral length. The procedure is then repeated in the opposite lobe.


The RF power that is delivered is 2 to 15 W for 5 minutes per lesion. In earlier models the treatment was begun at a low power, but now the whole thermal process is automated, with temperature levels at treatment areas preset. The temperature at the tip of the needle varies from 80° C to 100° C. The urethral temperature is kept below 46° C, and the temperature in the lesion is sustained for the treatment period.


At the end of the procedure, some urologists like to leave a urethral catheter in overnight; others do not put in a catheter and allow the patients to go home after they have voided and feel that they are emptying their bladder.



Clinical Results


Table 93–1 shows the results of the total world experience in the use of TUNA. There is a wide variety in the number of patients in each series and in the length of follow-up. Of note is that most are open series, with a minority of randomized studies (Issa and Oesterling, 2000). Although the inclusion and exclusion criteria are the same in most series, they are not exactly the same and are not as strict as those in studies testing α-adrenergic blockers and 5α-reductase inhibitors. The size of the studies varies from 12 to 130 patients, and, in many cases, the number of patients observed for the longest period of time consists of less than 50% of the original sample, which makes it difficult to draw definite conclusions. However, when looking at them all together, a number of points can be considered.



Table 93–1 Studies of Transurethral Needle Ablation with 12-Month Follow-up

image

A total of 546 patients have been observed for 12 months, with an increase in the mean PFR by an average of 6 mL/sec, representing an average improvement of 77%. The mean symptom score decreased by an average of 13.1 symptom units, which is an average improvement of 58%. Although there was consistency of the general improvements, there was a range. The greatest improvement in the mean PFR was 9.2 mL/sec (Giannakopoulos et al, 1996), and in the mean symptom score it was 15.4 symptom units (Steele and Sleep, 1997). The least improvement in mean PFR was 2.7 mL/sec (Rosario et al, 1997) and in symptom score it was 10.8 (Millard et al, 1996). Although the numbers in patients observed for longer are less (176 for 24 months and 88 for 36 months), the mean improvements appear to be maintained (Issa and Oesterling, 2000).


In the U.S. randomized trial comparing TUNA with TURP, 65 patients were treated by TUNA and 56 by TURP (Bruskewitz et al, 1998). At 1 year, 59 of the TUNA group (90%) and 47 of the TURP group (84%) were available for evaluation. In the TUNA group the symptom score improved from 24.7 to 11.1 (13.6 symptom units) and the PFR from 8.7 to 15.0 mL/sec (6.3 mL/sec). In the TURP group, the symptom score improved from 23.3 to 8.3 (15.0 symptom units) and the PFR improved from 8.4 to 20.8 mL/sec (12.4 mL/sec). The reasons for patients being lost to follow-up are clearly stated, but it was because of ineffectiveness in only 2 patients (3.1%) of the TUNA group and none of the patients treated by TURP. The treatment was found to be effective and safe. The complication rate of TUNA was low, in both the short and the long term; the most commonly reported adverse events were bleeding (32.3%), urinary tract infection (7.7%), and urethral stricture (1.5%). There was no adverse effect of any kind on sexual function in patients treated by TUNA.


There are some additional long-term studies that are of interest. Zlotta and coworkers (2003) entered 188 consecutive patients into a study; there were 5-year data on 121 of these. At the 5-year assessment, 41 of the 176 patients who were evaluable (2 dead, 10 lost to follow-up) required additional treatment after TUNA (23.3%). Although there were 5-year data on 121 patients, and this was defined as a 5-year follow-up, the 10 patients on whom there were only 4-year data were also included, giving a total of 131 patients. The mean IPSS decreased from 20.9 to 8.7, with tight standard deviations but a range at long-term follow-up of 2 to 20. The PFR improved from 8.6 to 12.1 mL/sec with a range at long-term follow-up of 6.5 to 19.2 mL/sec, once again giving the impression of quite a wide scatter of results. Although the drop in the mean IPSS is 12.2, which is an impressive decrease, the improvement in PFR is a less impressive decrease, being 3.5 mL/sec and comparable to that achieved by medical management at the same time point.


In another study from the United States (Hill et al, 2004), 121 men were enrolled in a prospective, randomized, multicenter clinical trial; 65 (54%) were randomly selected to receive TUNA and 56 (46%) were selected to receive TURP. It was reported that 9 of the 65 men (14%) required further intervention in the TUNA cohort, compared with 1 of the 56 men (2%) in the TURP cohort. The requirement for additional medical management in the TUNA cohort was not stated, presumably explaining the difference observed between this study and that described in the previous paragraph. Although this was reported as a 5-year study, only 18 of the 65 men in the TUNA group (28%) and 22 of the 56 (39%) in the TURP were evaluable at 5 years. This makes the 5-year data difficult to interpret despite the highly significant statistical differences described by the authors. At 3 years, the mean IPSS had decreased from 24.0 to 15.2 in the TUNA group and from 24.1 to 10.1 in the TURP group. The mean PFR had improved from 8.8 to 13.0 mL/sec in the TUNA group and from 8.8 to 19.1 mL/sec in the TURP group.


A cost comparison of medical management and TUNA for treating BPH over a 5-year period was performed by Naslund and colleagues (2005). They constructed a cost analysis model using published costs for tamsulosin, finasteride, TUNA, and TURP. They found that over the 5 years tamsulosin was less expensive than TUNA and that finasteride cost the same as TUNA. Combination therapy was more expensive, reaching a break-even point at 2 years and 7 months of treatment. The authors also calculated that TURP is more expensive than TUNA for achieving improvements in IPSS but less expensive for improving PFR.


A meta-analysis of trials of TUNA for treating symptomatic BPH has been reported (Boyle et al, 2004). Meta-analyses are dependent on the data that are put into them. In the case of TUNA, the trials analyzed were often poorly constructed, with inadequate numbers, and not randomized. In fact, there were 2 randomized trials, 2 nonrandomized observational protocols, and 10 single-aim observational studies. One thing that was consistent, however, was that in all studies the patients had severe LUTS, the mean IPSS at entry being greater than 20. The effect of TUNA was to halve the mean IPSS at 1 year. The shortage of long-term studies makes it difficult to draw specific conclusions, but although there was a tendency for the IPSS to increase in the long term the 50% decrease was maintained. The PFR increased by about 70% from baseline to 1 year. It tended to decline over time, but a 50% or greater improvement was maintained. One question has not been answered: although the mechanism of action of TUNA is an adequate explanation for the early improvements, how can it explain any positive long-term effect?



Pressure-Flow Studies


There have been six studies that examined relief of urodynamically proven obstruction as an end point, and these are summarized in Table 93–2. The number of patients in each group varies considerably (from 12 to 108), as does the length of follow-up. The largest number of patients are evaluable at 3 months (253), with smaller numbers having been observed to 12 months (140) or even longer. All patients had pressure-flow studies performed before and after treatment by TUNA.



Table 93–2 Pressure-Flow Studies after Transurethral Needle Ablation with 12-Month Follow-up

image

At 3 months the average detrusor pressure (Pdet) at PFR was 85.4 cm H2O, which 3 months after treatment had decreased to an average of 64.8 cm H2O (average decrease of 20%). The range at 3 months was 53.2 to 79.0 cm H2O. It is difficult to draw too many conclusions from these average figures because of the variability in each series, but they do point to the fact that there is a decrease in the Pdet at PFR in most series, if not quite relieving obstruction reliably in every case. At 12 months the average Pdet at PFR was 91.6 before treatment and 73.5 after treatment. In each series there was a small decrease in the difference that had been observed at 3 months.


In another urodynamic study (Minardi et al, 2001), a small number of patients (24) were observed to 24 months. The authors showed that there was initially no change in the prostatic volume or the prostate-specific antigen levels and that pressure-flow studies showed a reduction in the mean opening pressure and Pdet at PFR. This led them to speculate that the ideal patient for TUNA was a man younger than 70 years with a prostatic volume of less than 6 mL, with a pretreatment Pdet at PFR of less than 60 cm H2O and residual volume of less than 100 mL.




Reoperation


The reoperation rate must be compared with that of TURP. Although a 14% requirement for reoperation because of lack of efficacy of the primary treatment with TUNA may seem low, it occurred in less than 2 years (Schulman and Zlotta, 1995). In addition, the 12.7% incidence reported by Steele and Sleep (1997) occurred inside a 2-year period. In the multicenter study reported by Ramon and colleagues (1997), 9 of 76 patients were deemed to have experienced failure of the procedure because of an absence of improvement in PFR. Eight of these patients had no symptomatic improvement, but 5 had an improvement in quality of life.



Indications


The patient most likely to benefit from TUNA would be one who had lateral lobe enlargement and a prostate of 60 g or less (Naslund, 1997). Larger glands can be treated, but more time has to be spent treating each 1-cm segment. Patients with larger prostates, purely bladder neck hypertrophy, or median lobe enlargement are not ideal patients to be treated in this way, but they can be treated; for example, median lobe enlargement can be treated by rotating the TUNA catheter so that the needles point posteriorly, with special care being taken in assessing the depth of their penetration into the prostate.




Transurethral Microwave Therapy


Transurethral microwave therapy has been much evaluated in the past decade and has been widely used. Many urologists have a high regard for its usefulness in treating patients with LUTS, but, for many others, it has no place in the therapeutic line-up. TUMT has been examined clinically in many centers throughout the world, although the very large number of patients who have been entered into open noncomparative studies may surprise some urologists. The rationale for its effect on symptoms has also been studied carefully by authors from different centers, which is unlike that of many of the other so-called minimally invasive treatment modalities. In addition there has been an evolution in the technology of TUMT (Figs. 93-3 and 93-4), from low-energy to high-energy application, perhaps indicating that this technique has a future in the treatment of LUTS.



Tags:
Jun 4, 2016 | Posted by in ABDOMINAL MEDICINE | Comments Off on Minimally Invasive and Endoscopic Management of Benign Prostatic Hyperplasia

Full access? Get Clinical Tree
Get Clinical Tree app for offline access