Transurethral Hot Water Balloon Thermotherapy for Benign Prostatic Hyperplasia

Transcription

1 Transurethral Hot Water Balloon Thermotherapy for Benign Prostatic Hyperplasia Lance A. Mynderse, MD* and Thayne R. Larson, MD Address *Department of Urology, Mayo Foundation, 200 First Street, SW, Rochester, MN 55905, USA. Current Urology Reports 2003, 4: Current Science Inc. ISSN Copyright 2003 by Current Science Inc. For many years the transurethral prostatectomy has been the standard therapy for benign prostatic hyperplasia (BPH). In the past 10 to 15 years, a number of competing minimally invasive technologies (MIT) have been used to treat patients with symptomatic BPH. These heat-based treatments include transurethral microwave thermotherapy, interstitial devices (eg, interstitial laser coagulation and transurethral needle ablation), high-intensity focused ultrasound, and water-induced thermotherapy (WIT). This article reviews the evidence supporting the efficacy and safety of transurethral hot water balloon thermotherapy for BPH. Appropriate patient selection factors for WIT versus other MITs are reviewed. A novel combination therapy for adenocarcinoma of the prostate also is proposed. Introduction The frequency with which transurethral prostatectomy (TURP) is being performed in the United States is declining, but alternative minimally invasive technologies (MITs) are increasing [1]. This shift from an intervention for serious complications (urinary retention, uremia, and recurrent urinary tract infections) to therapy for relief of symptoms associated with bladder outlet obstruction has led to more medical management and minimally invasive therapies. The earliest contemporary use of heat therapy on the prostate dates back to the early 1980s. The goal of most thermotherapy devices is to produce coagulative necrosis in the obstructing prostatic tissue. The degree of tissue necrosis is controlled by the duration of exposure and the maximum temperature generated [2]. Among the most popular thermotherapies, transurethral microwave thermotherapy (TUMT), transurethral needle ablation (TUNA), and interstitial laser coagulation (ILC) have had a reasonably rigorous evaluation with acceptable safety and efficacy. Several newer modalities, including TherMatrix TMx-2000 (TherMatrix Inc., Bannockburn, IL) and water-induced thermotherapy (WIT) (Thermoflex system; ArgoMed Inc., Cary, NC), have less long-term efficacy data concerning side effects, retreatment, and durability. These two modalities represent heat therapies, which may create several millimeters of periurethral necrosis by marginal levels of thermotherapy and hyperthermia, but have not demonstrated the typical thermotherapy tissue temperatures and dwell of TUMT, TUNA, or ILC. The major common factor with these new MITs is the lack of long-term durability data from randomized, multicenter trials. To better identify the patients who would best benefit from WIT, this article presents the understanding of hot water balloon thermoablation for BPH. History The application of heat to treat BPH and prostatic disease is not new. In the 19th century, diathermy was advocated to heat the prostate [3]. In fact, the application of heat is an ancient medical tool used to relieve numerous medical complaints. In the early 1900s, the response of the male urethra to heat was characterized [3]. The use of therapeutic heat to the prostate for symptomatic BPH is thought to have been used first in 1985 by Yerushalmi et al. [4]. During the past decade, the concepts of hyperthermia (40 to 45ºC) and thermotherapy (> 45ºC) of the prostate have evolved. The focus of heat therapy is on reducing morbidity and improving long-term results. The development of MITs has been an evolving science. Similar to heat therapies, the concept of balloon dilatation of the prostatic urethra (BDP) is not new [5]. Although the mechanism for the temporary relief has never been elucidated completely, Castaneda et al. [6] postulated stretching of the prostatic capsule and anterior/posterior commissurotomies to be a significant element of this therapy. Several other mechanisms for BDP have been suggested. These include compression, dehydration and subsequent atrophy, and loss of smooth muscle tone with disruption of α-adrenergic receptors. Although initial studies suggested that balloon dilatation of the prostate may provide effective relief of bladder outlet obstructive symptoms, randomized, doubleblind studies have failed to show anything more than tempo-

2 288 Benign Prostatic Hyperplasia rary relief of symptoms. This modality has been eliminated from options offered to patients [7,8]. The combination of BDP and low-energy heating (ie, borderline thermotherapy versus hyperthermia and intraurethral balloon compression) represents the likely mechanism by which WIT exerts its influence on periurethral prostatic tissues. However, the intraprostatic balloon pressures of WIT differ markedly from those classically used for BDP (0.5 atm versus 3.5 atm). Early attempts to treat BPH independently with balloon dilatation or hyperthermia lacked efficacy and have been abandoned effectively. WIT may preserve elements of both as an underlying mechanism of action. Water-induced Thermotherapy Device Description The main components of the WIT system (ArgoMed Inc., Cary, NC) consist of the Thermoflex console and disposable WIT prostatic catheters (nine sizes; range, 2.0 to 6.0 cm in 0.5-cm increments). The WIT catheter allows continual circulation of heated water (60ºC) through a closed loop system from the heat element in the microprocessor-based control unit to the 0.5-atm, 50-F treatment balloon. The water is continuously monitored, heated, and circulated by an integrated peristaltic pump. The 18-F diameter treatment catheter shaft is thermally insulated, with air chambers to prevent conductive heating of nontargeted penile, membranous urethral, and sphincteric tissues. The 50-F balloon comes into direct contact with tissues of the prostatic urethra and is anchored by a standard latex-free, 18-cm 3 positioning balloon at the bladder neck. Inflation of the treatment balloon serves to maximize the exposed surface area of the prostate and to compress periurethral blood vessels. A typical treatment session includes a 2- to 3-minute ramp-up period of heating, an active therapy period of 37 minutes at 60ºC, and a 5-minute cooling phase (total of 45 minutes). The maximum depth of necrosis is 15 mm. As a result, the risk of heat penetration to nontarget tissues is minimal. Because heating is conductive, rectal thermometry is not necessary. Product literature recommends installation of 2% lidocaine local anesthesia per urethra without additional narcotics or sedation. At the end of the procedure, a temporary Foley catheter is inserted and left in place for 7 to 14 days. Device Trials and Reported Investigations Support for the safety and effectiveness of WIT to treat symptomatic BPH comes from three published studies. Nearly 4 years ago, Corica et al. [9 ] began an evaluation of 27 patients in Argentina. The patients were placed in four groups, each with a 45-minute treatment. Group 1 used a 50-F balloon at 60ºC, group 2 used a 60-F balloon at 60ºC, group 3 used a 60-F balloon at 62ºC, and group 4 used a 60-F balloon at 70ºC. After WIT, all of the patients had prostate tissue removed for histologic analysis; 24 of the patients underwent adenectomies and three underwent radical prostatectomies (mean, 27 days after treatment). The mean maximal depth of necrosis was 7, 9, 10.3, and 11mm in groups 1, 2, 3, and 4, respectively. The extent of necrosis increased with larger balloon size and water temperature. Investigators think treatment balloon inflation to 60 F was most significant and resulted in 25% more heat energy delivery into the prostate. It is speculated that larger thermal dosages were accomplished by a compression of periurethral vasculature, lessening the heat sink effect of the periurethral vascular tissue. Studies with TUMT have noted that the ratio of glands to stroma had little effect on outcome [10]. A more vascular prostate or one with robust blood flow may preclude adequate therapy because of this phenomenon [11]. In the only prospective, multicenter trial with WIT, Muschter et al. [12 ] observed 125 patients using the 50-F balloon at 60ºC for 45 minutes. Significant improvement in peak urinary flow rates, the International Prostate Symptom Score (IPSS), and quality-of-life scores were observed as early as 3 months after treatment. At 12 months, the IPSS improved by a median of 12.5 versus baseline. Quality-of-life scores improved by 2.5 and peak urinary flow rates improved by 6.4 cm 3 /sec. At 12 months, IPSS, peak urinary flow, and quality of life improved by more than 50% in 61.5%, 71.3%, and 71.6% of patients, respectively. Serious adverse events were infrequent, although nearly one third of the patients were treated for urinary tract infections. No adverse impact was noted on sexual function. Three-year and preliminary 4-year data for this same cohort [13] were presented at the American Urological Association in Orlando, May 2002 (Table 1). Breda and Isgro [14 ] presented a single-institution experience with WIT in 50 patients with an average followup of 11 months. Twenty-four patients had chronic indwelling Foley catheters placed before treatment and 19 of 24 (79%) resumed spontaneous voiding after therapy. No statistical difference in IPSS, flow rate, and quality of life was noted between two treatment groups (ie, 60ºC/50 F and 62ºC/60 F), although no tissue was examined to quantify the depth of necrosis. Building on speculation of the study by Corica et al. [9 ], a series of magnetic resonance images (MRIs) in an unpublished South American cohort detail the gadolinium defect seen after WIT. The preliminary analysis supports the observation that larger balloon size and hotter temperatures are needed to create more tissue destruction. These studies validate the need for balloon diameters of at least 60 F and water temperatures higher than 60ºC. Discussion In the more than 50 years since its introduction, TURP has become the standard definitive therapy for BPH because it improves voiding function and ameliorates obstructive and irritative symptoms. TURP is not a suitable treatment for many patients because some may be at poor surgical risk or have an aversion to an invasive surgical procedure. A corre-

3 Transurethral Hot Water Balloon Therapy Mynderse and Larson 289 Table 1. Peak urinary flow, postvoid residual, symptom score, and quality of life at the 3-year follow-up in water-induced thermotherapy European Multicenter Clinical Study Baseline, n = months, n = months, n = months, n = months, n = months, n = 68 (preliminary) Peak flow cm 3 /sec Postvoid cm Symptom score (International Prostate Symptom Score) Quality of life Adapted from ArgoMed Inc. [13]. Figure 1. Risk-benefit association among treatment options for benign prostatic hyperplasia. ILC interstitial laser coagulation; HoLep holmium laser enucleation of the prostate; PVP photoselective laser vaporization of the prostate; T treatment; TUIP transurethral incision of the prostate; TUNA transurethral needle ablation; TURP transurethral resection of the prostate; WIT water-induced thermotherapy. lation exists between the potential for benefit and the risk of complications (Fig. 1). Open surgery may entail postoperative complications in up to 21% of patients, with symptomatic improvement ranging from 100% to 175%. Longterm medical management yields up to 26% improvement in symptoms [15]. Minimally invasive therapies offer patients an acceptable risk with the prospect of achieving substantial improvement in their quality of life. The search continues for the ideal MIT. Such a treatment would be well tolerated and effective immediately, with limited risk and durable effect. Among the available treatment options, WIT offers certain advantages and limitations. It is applicable to those who are medically fragile and are at poor surgical risk. In almost all cases, WIT can be accomplished with local anesthesia. The technique is simple to administer with a short learning curve and is not operator-dependent. The technology is applicable to a full range of prostatic urethral lengths. The limitations of WIT relate to its restricted destruction profile of periurethral necrosis and its lack of applicability to asymmetric intravesical tissue. Additionally, only sparse long-term efficacy data from randomized trials are available; no sham studies have been conducted. In general, there are at least three postulated theories to explain the mechanism of action of WIT and how to explain its success: 1. The neuromuscular elements, including α-adrenergic receptors in the periurethral area, are damaged by the heat causing the tissue around the urethra to relax, which reduces the sensory signals of the urge to void 2. An increase in WIT prostatic balloon pressure promotes heat transfer by tissue compression, reducing the heat sink effect of the periurethal vasculature 3. Recent South American MRI studies hypothesize the presence of a noncontractile, rigid, fibrotic, periurethral capsule, which may act as a biologic stent resisting compression from surrounding prostatic hyperplastic tissue If the variable of balloon dilatation pressure provides this technology with an avenue of feedback from the treated prostate, this mode of therapy may provide the prospect of an enhanced technology with increased necrosis and durable results. This real-time feedback may adjust for different qualities of prostate density, vascular supply, and fibromuscular tone. Conceivably, by this dynamic control of

4 290 Benign Prostatic Hyperplasia WIT balloon pressure, the degree of treated tissue would increase the area of necrosis. High-energy microwave technologies (Targis [Urologix, Minneapolis, MN] and Prostatron [EDAP; Cambridge, MA]) indirectly adjust power and cooling levels to accommodate feedback from urethral and rectal thermal sensors. Prostalund (ProstaLund Operations AB, Sweden) uses an intraprostatic temperature feedback sensor to similarly optimize therapy. Early findings are encouraging from several other companies conducting research with hot water balloons at higher temperatures and shorter treatment times. The pressure control mechanism postulated by WIT may offer another control avenue to enhance prostatic tissue destruction and subsequent relief of obstructive BPH symptoms. Further multicenter, randomized, controlled studies would be essential to validate these mechanisms. Heat Therapies and Prostate Cancer As with BPH, minimally invasive therapies for prostate cancer also have become popular alternatives to invasive surgery. Interstitial, transperineal brachytherapy and cryotherapy have become a mainstay of treatment for those patients with newly diagnosed prostate cancer. In a recent study by Leibovich et al. [16 ], the proximity of prostate cancer to the urethra in 350 whole-mounted radical prostatectomy specimens was evaluated. In this study, 17% of these patients had cancer that touched the urethra. The distance between the urethra and the nearest cancer cells was predictive and associated with cancer recurrences. This study has significant implications for urethral sparing, minimally invasive prostate cancer therapies. In cryotherapy, urethral sparing is achieved by a urethral warmer. In many interstitial brachytherapy plans for the prostate, the urethra receives a reduced radiation dose to limit irritative voiding symptoms. One can envision the concept of a combined prostate cancer treatment plan in which the periurethal prostate tissue is treated by an ablative heat technology such as WIT before or after therapy with radiation or cryotherapy. Conclusions During the past decade, heat treatment for symptomatic BPH has become a cost-effective reality. TUMT has taken the lead in numerous studies unequivocally supporting its efficacy and safety. Compared with long-term medical management, minimally invasive procedures offer well-tolerated, one-time durable effects. WIT is a relatively recent member of the MIT armamentarium. In comparing TUMT with WIT, the latter appears to result in less ablated prostate volume and may have more urethral necrosis. An unresolved argument persists regarding the value of urethral preservation. Patient comfort, cost effectiveness, and reimbursement will invariably dictate the inclusion of low-energy heat therapies (WIT, TherMatrx) in the selection of MIT for symptomatic BPH. The concept of balloon pressure control as an avenue to influence tissue necrosis is intriguing, but prospective, randomized studies are essential to elucidate the future role of this heat technology. As the numbers of new BPH treatment technologies grow, alternative applications such as adjunctive therapy to already effective minimally invasive prostate cancer treatments should be entertained [17 ]. References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Of importance Of major importance 1. Lu-Yao GL, Barry MJ, Chang CH, et al.: Transurethral resection of the prostate among Medicare beneficiaries in the United States: time trends and outcomes. Prostate Patient Outcomes Research Team (PORT). Urology 1994, 44: Laguna MP, Muschter R, Debruyne FMJ: Microwave thermotherapy: historical overview. J Endourol 2000, 14: Edwards LE: History of non-surgical treatment. In Benign Prostatic Hypertrophy. Edited by Hinman F Jr. New York: Springer- Verlag; 1983: Yerushalmi A, Fishelovitz Y, Singer D, et al.: Localized deep microwave hyperthermia in the treatment of poor operative risk patients with benign prostatic hyperplasia. J Urol 1985, 133: Hollingsworth E: Dilatation of the prostatic urethra for the relief of the symptoms of prostatic enlargement. Ann Surg 1910, 51: Castaneda F, Isorna S, Hulbert JC, et al.: The importance of separation of prostatic lobes in relief of prostatic obstruction by balloon catheter urethroplasty: studies in dogs and humans. AJR 1989, 153: Lepor H, Sypherd D, Machi G, Derus J: Randomized doubleblind study comparing the effectiveness of balloon dilation of the prostate and cystoscopy for the treatment of symptomatic benign prostatic hyperplasia. J Urol 1992, 147: Donatucci CF, Berger N, Kreder KJ, et al.: Randomized clinical trial comparing balloon dilatation to transurethral resection of prostate for benign prostatic hyperplasia. Urology 1993, 42: Corica FA, Cheng L, Ramnani D, et al.: Transurethral hotwater balloon thermoablation for benign prostatic hyperplasia: patient tolerance and pathologic findings. Urology 2000, 56: This is the first clinical study to use WIT and show pathologic evidence of tissue effect on BPH. 10. Siegel YI, Zaidel L, Hammel I, et al.: Histopathology of benign prostatic hyperplasia after failure of hyperthermia treatment. Br J Urol 1991, 68: Larson TR, Collins JM: An accurate technique for detailed prostatic interstitial temperature-mapping in patients receiving microwave thermal treatment. J Endourol 1995, 9: Muschter R, Schorsch I, Danielli L, et al.: Transurethral waterinduced thermotherapy for the treatment of benign prostatic hyperplasia: a prospective multicenter clinical trial. J Urol 2000; 164: The first and only prospective, multicenter clinical trial for WIT and BPH. 13. ArgoMed Incorporated: Clinical results. Accessed January 14, 2003.

5 Transurethral Hot Water Balloon Therapy Mynderse and Larson Breda G, Isgro A: Treatment of benign prostatic hyperplasia with water-induced thermotherapy: experience of a single institution. J Endourol 2002, 16: A single-institution experience with WIT and patients in urinary retention. 15. McConnell JD, Barry MJ, Bruskewitz RC, et al.: Benign prostatic hyperplasia: diagnosis and treatment. Clinical practice guideline, Number 8; Agency for Health Care Policy and Research, Public Health Service, US Dept of Health and Human Services, Rockville, MD AHCPR Publication No (February 1994) 16. Leibovich BC, Blute ML, Bostwick DG, et al.: Proximity of prostate cancer to the urethra: implications for minimally invasive ablative therapies. Urology 2000, 56: A large pathologic study for prostate cancer showing urethral proximity for prostate cancer and recurrence rates. 17. Larson TR: Rationale and assessment of minimally invasive approaches to benign prostatic hyperplasia therapy. Urology 2002, 59: An evidence-based review of the minimally invasive treatment choices for BPH.