Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.

PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezum® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

Two-year results after convective radiofrequency water vapor thermal therapy of symptomatic benign prostatic hyperplasia.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of convective radiofrequency (RF) water vapor thermal therapy in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH); a pilot study design with 2-year follow-up evaluations. PATIENTS AND METHODS: Men aged ≥45 years with an International Prostate Symptom Score ≥13, a maximum urinary flow rate (Qmax) ≤15 mL/s, and prostate volume 20-120 cc were enrolled in a prospective, open-label pilot study using convective RF water vapor energy with the Rezum System. Patients were followed up for 2 years after transurethral thermal treatment at 3 international centers in the Dominican Republic, Czech Republic, and Sweden. The transurethral thermal therapy utilizes radiofrequency to generate wet thermal energy in the form of water vapor injected through a rigid endoscope into the lateral lobes and median lobe as needed. Urinary symptom relief, urinary flow, quality of life (QOL) impact, sexual function, and adverse events (AEs) were assessed at 1 week, 1, 3, 6, 12, and 24 months. RESULTS: LUTS, flow rate, and QOL showed significant improvements from baseline; prostate volumes were appreciably reduced. Sexual function was maintained and no de novo erectile dysfunction occurred. The responses evident as early as 1 month after treatment remained consistent and durable over the 24 months of study. Early AEs were typically transient and mild to moderate; most were related to endoscopic instrumentation. No procedure related to late AEs were seen. CONCLUSION: The Rezum System convective RF thermal therapy is a minimally invasive treatment for BPH/LUTS which can be performed in the office or as an outpatient procedure with minimal associated perioperative AEs. It has no discernable effect on sexual function and provides significant improvement of LUTS that remain durable at 2 years.

Erectile and Ejaculatory Function Preserved With Convective Water Vapor Energy Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Randomized Controlled Study.

INTRODUCTION: Most surgical treatments for male lower urinary tract symptoms and benign prostatic hyperplasia affect erectile and ejaculatory functions negatively, leading to patient dissatisfaction. AIM: To determine whether water vapor thermal therapy, when conducted in a randomized controlled trial, would significantly improve lower urinary tract symptoms secondary to benign prostatic hyperplasia and urinary flow rate while preserving erectile and ejaculatory functions. METHODS: Men at least 50 years old with International Prostate Symptom Scores of at least 13, a peak flow rate of at least 5 to no higher than 15 mL/s, and prostate volume of 30 to 80 cm(3) were randomized 2:1 between Rezum System thermal therapy and control. Thermal water vapor (103°C) was injected into lateral and median lobes as required for treatment of benign prostatic hyperplasia. The control procedure entailed rigid cystoscopy with simulated active treatment sounds. MAIN OUTCOME MEASURES: Blinded group (active = 136, control = 61) comparison occurred at 3 months and the active arm was followed to 12 months for International Prostate Symptom Score, peak flow rate, and sexual function using the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. The minimal clinically important difference in erectile function perceived by subjects as beneficial was determined for each erectile function severity category. Subjects not sexually active were censored from sexual function analysis. RESULTS: No treatment- or device-related de novo erectile dysfunction occurred after thermal therapy. International Index of Erectile Function and Male Sexual Health Questionnaire for Ejaculatory Function scores were not different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved 31% over baseline (P = .0011). Also, 32% of subjects achieved minimal clinically important differences in erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile dysfunction. International Prostate Symptom Score and peak flow rate were significantly superior to controls at 3 months and throughout 1 year (P < .0001). CONCLUSION: Convective water vapor thermal therapy provides sustainable improvements for 12 months to lower urinary tract symptoms and urinary flow while preserving erectile and ejaculatory functions.

Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezum® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. RESULTS: There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. CONCLUSIONS: Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe.

Rezum System Water Vapor Treatment for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Validation of Convective Thermal Energy Transfer and Characterization With Magnetic Resonance Imaging and 3-Dimensional Renderings.

OBJECTIVE: To evaluate by magnetic resonance imaging the physical effects of convective thermal energy transfer with water vapor as a means of treating lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: Sixty-five men with lower urinary tract symptoms were treated with the Rezum System by transurethral intraprostatic injection of water vapor. A group of 45 of these men consented to undergo a series of gadolinium-enhanced magnetic resonance imagings of the prostate after treatment to monitor the size and location of ablative lesions, their time course of resolution, and the corresponding change in prostate tissue volume. Visualization was conducted at 1 week, 1, 3, and 6 months after treatment. RESULTS: Outcomes were available for 44 patients. Convective thermal lesions were limited to the transition zone and correlated with targeted treatment locations. At 1 week after treatment, the mean volume of ablative lesions was 8.2 cm(3) (0.5-24.0 cm(3)). At 6 months, whole prostate volume was reduced by a mean of 28.9% and transition zone volume by 38.0% as compared with baseline 1-week images. At 3 and 6 months after treatment, the lesion volumes had reduced by 91.5% and 95.1%, respectively. Lesions remained within the targeted treatment zone without compromising integrity of the bladder, rectum, or striated urinary sphincter. CONCLUSION: This imaging study confirms the delivery of convective water vapor technology to create thermal lesions in the prostate tissue. Lesions generated underwent near complete resolution by 3 and 6 months after treatment with a concomitant one-third reduction in overall prostate and transition zone volumes.

Transurethral convective water vapor as a treatment for lower urinary tract symptomatology due to benign prostatic hyperplasia using the Rezum(®) system: evaluation of acute ablative capabilities in the human prostate.

BACKGROUND: The purpose of this study was to assess the acute ablative characteristics of transurethral convective water vapor (steam) using the Rezum(®) system in men with benign prostatic hyperplasia through histologic and radiographic studies. METHODS: Seven patients were treated with transurethral intraprostatic injections of sterile steam under endoscopic visualization followed by previously scheduled adenectomies. The extirpated adenomas were grossly examined followed by whole mount sectioning and staining with triphenyl-tetrazolium chloride (TTC) to evaluate thermal ablation. Histology was performed after hematoxylin and eosin staining on one prostate. After review of results from the first patient cohort, an additional 15 patients with clinical benign prostatic hyperplasia were treated followed by gadolinium-enhanced magnetic resonance imaging (MRI) at one week. RESULTS: In the first patient cohort, gross examination of TTC-stained tissue showed thermal ablation in the transition zone. In addition, there was a distinct interface between viable and necrotic prostatic parenchyma. Histopathologic examination revealed TTC staining-outlined necrotic versus viable tissue. Gadolinium-enhanced MRIs in the cohort of 15 patients demonstrated lesion defects in all patients at 1 week post-procedure. Coalesced lesions were noted with a mean (± standard deviation) lesion volume of 9.6±8.5 cm(3). The largest lesion volume was 35.1 cm(3). Ablation using vapor was rapid and remained confined to the transition zone, consistent with the thermodynamic principles of convective thermal energy transfer. CONCLUSION: Thermal ablation was observed in all specimens. The resulting coalescing ablative lesions, as seen on MRI, were confined to the transition zone. These studies confirm the ablative capabilities of vapor, validate the thermodynamic principles of convective heating, and allow for further clinical studies.

Initial human feasibility study of DC ablation as a treatment for benign prostatic hyperplasia: 6 month follow-up data.

Direct current (DC) ablation is a novel non-thermal technology that causes focused coagulative necrosis in the lateral lobes of the prostate to treat benign prostatic hyperplasia (BPH). The necrosis is caused by a zone of non-physiologic pH which is created in a predictable pattern around each electrode in which a direct current is applied during treatment. The objective of this study was to optimize treatment parameters and assess treatment tolerability using transurethral DC ablation as an office-based treatment for BPH.

Characterizing Prostiva RF treatments of the prostate for BPH with gadolinium-enhanced MRI.

Transurethral needle ablation (TUNA) is an accepted and effective therapy for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Prostiva (Medtronic, Shoreview, MN) is the newest-generation device, which includes a new needle design and radio frequency (RF) generator. This device creates temperatures of 120 degrees C and necrotic lesions in less than 2.5 min. Using previously described techniques, we analyzed dynamic, gadolinium-enhanced MRIs to characterize the ablative properties of the new Prostiva RF device. Ten men with LUTS due to BPH were treated with the standard Prostiva manufacturer-recommended protocol. The bladder neck and lateral lobes received treatment based on prostate volume and prostatic urethral length. Gadolinium-enhanced MRI sequences were obtained prior to and 1 week post-treatment. Analyze software (Mayo Clinic Biomedical Imaging Resource, Rochester, MN) was used to evaluate MRIs. New gadolinium defects were seen in all patients following Prostiva treatments. All lesions coalesced within the prostate. No defects were seen beyond the prostate, and the urethra was spared in all patients. The mean volume of necrosis was 7.56 cc, representing a mean of 11.28% of total prostate volume. Dynamic, gadolinium-enhanced MRIs demonstrate new vascular defects representing necrosis caused by Prostiva RF therapy of the prostate. The standard Prostiva RF protocol produces lesions that coalesce to create larger lesions in the bladder neck and lateral lobes. Compared to the TUNA Precision Plus device, the ablative lesions appear comparable while produced with a shorter burn time.

Blood pressure surges during office-based transurethral microwave therapy for the prostate.

OBJECTIVE: To investigate the occurrence of adverse blood pressure (BP) events during transurethral microwave therapy (TUMT) for benign prostatic hyperplasia. PATIENTS AND METHODS: We conducted a retrospective study of the vital signs of 185 consecutive patients who received TUMT (via 6 devices) at 4 institutions from March 1, 2003, to September 18, 2005. Maximum change, percent change in systolic BP, diastolic BP, mean arterial pressures, heart rate, and oxygen saturation were evaluated. RESULTS: Of the 185 patients, 77 patients (42%; 95% confidence interval [CI], 35%-49%) experienced an increase in systolic BP of more than 30 mm Hg during TUMT; 30 patients (16%; 95% CI, 12%-22%), an increase of more than 50 mm Hg; and 10 patients (5%; 95% CI, 3%-10%), an increase of more than 70 mm Hg. A greater than 20% change in systolic BP from baseline was observed in 95 patients (51%; 95% CI, 44%-58%). Many men experienced multiple events, with an average time of onset of 15.9 minutes into treatment. Significant differences were noted among the devices. CONCLUSION: This retrospective study demonstrates a significant number of BP surges during TUMT for benign prostatic hyperplasia. These BP changes represent a potential risk of cardiovascular events in patients with known or occult cardiovascular disease. Our study is the first to recognize the incidence of this BP response. Until further studies identify the mechanisms responsible for these surges in BP, the results of this study suggest that BP should be monitored, treatment adjusted, and antihypertensive medications continued during all TUMT.

Interstitial temperature mapping during Prolieve transurethral microwave treatment: imaging reveals thermotherapy temperatures resulting in tissue necrosis and patent prostatic urethra.

OBJECTIVES: Temperature mapping of the prostate during transurethral microwave thermotherapy and imaging of the resultant zones of tissue necrosis have been previously performed using several commercial systems. This study was performed using the Prolieve Thermodilatation System, which simultaneously compresses the prostate with a 46F balloon circulating heated fluid and delivering microwave energy into the prostate. METHODS: Interstitial temperature mapping during Prolieve treatment was performed on 10 patients with benign prostatic hyperplasia using 24 temperature sensors arrayed throughout the prostate. Voiding cystourethrograms were performed on 3 additional patients treated without temperature mapping to document the patency of the prostatic urethra 1 hour after treatment. Gadolinium-enhanced magnetic resonance imaging studies were performed on all patients 1 week after treatment to determine the extent and pattern of tissue necrosis resulting from transurethral microwave thermotherapy. RESULTS: Interstitial temperature mapping found that the heating pattern generated by the Prolieve system created average peak temperatures of 51.8 degrees C an average of 7 mm away from the prostatic urethra. These temperatures were greater near the bladder neck and mid-gland than toward the prostatic apex. Subtherapeutic temperatures were seen adjacent to the urethra, consistent with the viable tissue seen on gadolinium-enhanced magnetic resonance imaging sequences. Magnetic resonance imaging also revealed necrotic zones that were consistent with sustained temperatures greater than 45 degrees C. Voiding cystourethrograms showed widely patent prostatic urethras 1 hour after treatment. CONCLUSIONS: Transurethral microwave thermotherapy with the Prolieve Thermodilatation System produced sustained therapeutic temperatures that resulted in tissue necrosis while maintaining viable tissue surrounding a temporarily dilated prostatic urethra.

Transurethral microwave thermotherapy effectiveness in small prostates.

OBJECTIVES: To dispel the misconceptions that patients with small prostates react differently than patients with larger prostates to cooled transurethral microwave thermotherapy. Cooled transurethral microwave thermotherapy has developed into a valid alternative to treat men with lower urinary tract symptoms due to benign prostatic hyperplasia. However, doubts still remain regarding the ability of this office-based technique to treat smaller prostates. METHODS: A database of 713 men from six previous studies using cooled transurethral microwave thermotherapy devices developed by Urologix were combined for this analysis. The data were analyzed to determine whether the baseline prostate size had a significant effect on American Urological Association Symptom Index, peak flow rate, quality-of-life score, or symptom problem index. Follow-up intervals in this analysis include 6, 12, 24, 36, 48, and 60 months after therapy. Visual analog scale ratings during treatment were also assessed. General linear models and repeated measures analyses were performed. RESULTS: Statistical analysis showed no effect of baseline prostate size on treatment outcomes for more than 5 years. Visual analog scale measurements were also not affected by the baseline prostate size. CONCLUSIONS: Transurethral microwave thermotherapy appears to be as efficacious in treating patients with small prostates as those with large prostates and should be offered as a treatment modality to patients with prostates of all sizes.

Intraprostatic injection of alcohol gel for the treatment of benign prostatic hyperplasia: preliminary clinical results.

Benign prostatic hyperplasia (BPH) is one of the most common diseases ailing older men. Office-based procedures offer the advantage of being more effective than medications, while limiting the adverse effects, cost, and recovery of surgery. This study presents preliminary data on a new procedure that utilizes intraprostatic alcohol gel injection to ablate prostatic tissue. The purpose of this study is to evaluate the feasibility of using this gel as a treatment for BPH. A total of 65 patients with lower urinary tract symptoms (LUTS) due to BPH were treated with intraprostatic injections of alcohol gel. The gel is composed of 97% denatured alcohol and a patented polymer to cause viscosity. Three different methods of injection were utilized: transrectal (TR) injections (8), transurethral (TU) injections (36), and transperineal (TP) injections guided by biplaned ultrasound (21). Each method provided easy access to the center of the prostate, where a volume of gel, approximately 20-30% of the prostatic volume, was injected. Follow-up was based on changes in peak urinary flow (Qmax), IPSS scores, quality of life scores (QoL), adverse effects, and failures. Data are available at 3 and 12 months. The procedure was well tolerated with only local or no anesthesia in the TR and TP groups; the TU group received spinal anesthesia. All groups showed statistically significant (p < 0.0001) improvements in Qmax, IPSS, and QoL. The mean amount of gel injected was 8.05 ml, representing 21.56% of the prostatic volume. Qmax increased from a baseline mean of 8.50 to 12.01 ml/s at 3 months, and to 11.29 ml/s at 12 months. IPSS scores improved from a baseline mean of 21.12 to 10.00 at 3 months, and to 11.84 at 12 months. QoL scores were only available for 55 patients. QoL scores improved from a baseline of 3.93 to 1.98 at 3 months, and to 2.18 at 12 months. No extraprostatic injury or adverse effects were reported due to treatment. This preliminary study presents significant results showing that intraprostatic injection of alcohol gel could be an option for the treatment of BPH and LUTS. The viscosity of the gel allows for accurate imaging under ultrasound, no run back along the needle allowing for multiple methods of delivery, and the gel does not spread to extraprostatic tissue. This new technique could provide a simple and possibly less expensive clinic procedure for treating BPH, and warrants further study.

Long-term pooled analysis of multicenter studies of cooled thermotherapy for benign prostatic hyperplasia results at three months through four years.

OBJECTIVES: To determine the long-term efficacy of cooled thermotherapy in the treatment of lower urinary tract symptoms of clinical benign prostatic hyperplasia. METHODS: A total of 541 men underwent cooled thermotherapy treatment in six multicenter studies in the United States, England, and Canada. Both fixed and random effects models were used to pool the data across the six studies. The treatment response was measured as the difference between the urinary tract symptoms at baseline versus those at 3, 12, 24, 36, and 48 months after therapy. The treatment response included changes in the American Urological Association Symptom Score (AUA symptom score), peak urinary flow rate in milliliters per second (Qmax), and quality of life (QOL). RESULTS: The baseline measures were comparable across the studies. At 3 months, the AUA symptom score had improved by a mean of 11.6 (55%), Qmax by a mean of 4.0 (51%), and QOL by a mean of 2.3 (53%). These changes persisted with only slight attenuation through 48 months (corresponding mean changes of 43%, 35%, and 50%). These changes were highly statistically significant (P <0.0001 to 0.01). An improvement of at least 25% was achieved for the AUA symptom score and QOL by more than 85% of men and by more than 65% of men for Qmax. CONCLUSIONS: This pooled analysis of six multicenter studies of cooled thermotherapy, involving 541 men, found highly significant improvements in AUA symptom score, Qmax, and QOL. The results were highly consistent across the studies. The improvements reflected changes from baseline values of 45% to 50% for AUA symptom score and QOL and 35% to 40% for Qmax at a follow-up duration up to 48 months after therapy. The level of improvement for all three measures remained high at 48 months, indicating that the response is durable.

Histological changes of minimally invasive procedures for the treatment of benign prostatic hyperplasia and prostate cancer: clinical implications.

PURPOSE: Benign prostatic hyperplasia (BPH) is near universal in aging men, creating tremendous costs in morbidity and surgical treatment. In the last decade numerous nonsurgical minimally invasive methods have emerged for ablation of prostatic tissue. MATERIALS AND METHODS: We reviewed the recently published English language literature on minimally invasive techniques for treating BPH and cancer with an emphasis on histopathological findings. RESULTS: We compared the spectrum of contemporary minimally invasive treatments for BPH and cancer, with an emphasis on histopathological results. Clinical results were summarized briefly for each treatment method. These procedures ablate tissue by thermal, cryogenic, chemical or enzymatic injury. The 5-year results for some techniques were promising, although long-term durability is still uncertain, and other methods were in preclinical or early clinical stages. Invariably the treated tissue was devitalized with a thin border of granulation tissue and fibrosis. These procedures have applications for BPH and prostate cancer, although some studies are limited to only 1 disease. CONCLUSIONS: Minimally invasive procedures show promise of a durable replacement for surgical resection.

Rationale and assessment of minimally invasive approaches to benign prostatic hyperplasia therapy.

Benign prostatic hyperplasia affects quality of life, with most patients complaining of symptoms related to urination. For this reason, successful treatments can be defined by (1) their effect on lower urinary tract symptoms, (2) their impact on quality of life, and (3) their ability to unobstruct the flow of urine through the prostate. Minimally invasive therapy (MIT), which includes transurethral microwave thermotherapy, water-induced thermotherapy, interstitial devices (eg, transurethral needle ablation), and interstitial laser treatments, offers physicians and their patients cost-effective alternatives for achieving a substantially improved quality of life at an acceptable level of risk. Evidence-based medicine indicates that MIT is safe and achieves significant symptomatic improvement. Compared with long-term medical management, minimally invasive procedures offer effective, well-tolerated 1-time intervention with lasting effects that can be achieved on an outpatient basis. This article reviews the options for MIT.