Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.

Acoustoelasticity Analysis of Transient Waves for Non-Invasive In Vivo Assessment of Urinary Bladder.

A non-invasive method for measurement of the bladder wall nonlinear elastic behavior is presented. The method is based on acoustoelasticity modeling of the elasticity changes in bladder tissue modulus at different volumetric strain levels. At each volume, tissue strain is obtained from the real-time ultrasound images. Using acoustic radiation force, a transient Lamb wave is excited on the bladder wall and instantaneous modulus of shear elasticity is obtained from the 2-D Fourier analysis of the spatial-temporal dispersion maps. Measured elasticity and strain data are then used in an acoustoelasticity formulation to obtain the third order elastic coefficient, referred to as nonlinearity parameter A, and initial resting elasticity µ0. The method was tested in ex vivo porcine bladder samples (N = 9) before and after treatment with formalin. The estimated nonlinearity parameter, A, was significantly higher in the treated samples compared to intact (p < 0.00062). The proposed method was also applied on 16 patients with neurogenic bladders (10 compliant and 6 non-compliant subjects). The estimated nonlinearity parameter A was significantly higher in the non-compliant cases compared to the compliant (p < 0.0293). These preliminary results promise a new method for non-invasive evaluation of the bladder tissue nonlinearity which may serve as a new diagnostic and prognostic biomarker for management of the patients with neurogenic bladders.

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease.

BACKGROUND: Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE: To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION: C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS: Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS: CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY: We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

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.

Efficacy and Safety of Rezum System Water Vapor Treatment for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

OBJECTIVE: To assess 1-year efficacy and safety data from pilot trials of the Rezum System water vapor to treat lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 65 men with symptoms of moderate to severe BPH were enrolled in pilot studies at centers in the Dominican Republic, the Czech Republic, and Sweden. Each patient was treated with transurethral delivery of sterile water vapor (steam). International Prostate Symptom Score (IPSS), peak urinary flow (Qmax), quality of life (QoL), postvoid residual, International Index of Erectile Function, and prostate-specific antigen were evaluated at 1 week and 1, 3, 6, and 12 months post-treatment. Safety was also assessed. RESULTS: Statistically significant clinical improvements at 1, 3, 6, and 12 months were reported for IPSS (decreased by 6.8, 13.4, 13.1, and 12.5 points, respectively) and Qmax (increased by 2.0, 4.7, 4.3, and 4.6 mL/sec, respectively). At 12 months, these results equated to a 56% improvement in IPSS (P <.001) and an 87% improvement in Qmax (P <.001). QoL also improved at 12 months with a 61% improvement. Sexual function was maintained. Most of the adverse events (AEs) were related to endoscopic instrumentation and were of short duration. One case of urinary retention was classified as a procedure/device-related serious AE. CONCLUSION: The Rezum System provides effective relief of LUTS associated with BPH at 1 year. The procedure is safe with an acceptable side effect profile.

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.

Holmium laser enucleation (HoLEP) and photoselective vaporisation of the prostate (PVP) for patients with benign prostatic hyperplasia (BPH) and chronic urinary retention.

OBJECTIVES: To evaluate short-term outcomes of holmium laser enucleation of the prostate (HoLEP) and photoselective vaporisation of the prostate (PVP) in patients with benign prostatic hyperplasia (BPH) and chronic urinary retention (CUR). PATIENTS AND METHODS: A retrospective chart review was performed of all patients with CUR who underwent HoLEP or PVP at our institution over a 3-year period. CUR was defined as a persistent post-void residual urine volume (PVR) of >300 mL or refractory urinary retention requiring catheterisation. RESULTS: We identified 72 patients with CUR who underwent HoLEP and 31 who underwent PVP. Preoperative parameters including median catheterisation duration (3 vs 5 months, P = 0.71), American Urological Association Symptom Index score (AUASI; 18 vs 21, P = 0.24), and PVR (555 vs 473 mL, P = 0.096) were similar between the HoLEP and PVP groups. The HoLEP group had a larger prostate volume (88.5 vs 49 mL, P < 0.001) and higher PSA concentration (4.5 vs 2.4 ng/mL, P = 0.001). At median 6-month follow-up, 71 (99%) HoLEP patients and 23 (74%) PVP patients were catheter-free (P < 0.001). Of the voiding patients, postoperative AUASI (3 vs 4, P = 0.06), maximum urinary flow rate (23 vs 18 mL/s, P = 0.28) and PVR (56.5 vs 54 mL, P = 1.0) were improved in both groups. CONCLUSIONS: Both HoLEP and PVP are effective at improving urinary parameters in men with CUR. Despite larger prostate volumes, HoLEP had a 99% successful deobstruction rate, thus rendering patients catheter-free.

Urethral injury during potassium-titanyl-phosphate laser prostatectomy complicated by transurethral resection syndrome.

The green light potassium-titanyl-phosphate laser photoselective vaporization of the prostate is the latest modality for treatment of benign prostatic obstruction. Because of effective superficial tissue coagulation, intravascular absorption of fluid is minimal; therefore, development of transurethral resection syndrome is unlikely. To our knowledge, this is the first report of a patient undergoing photoselective vaporization of the prostate who developed full-blown transurethral resection syndrome because of intravascular absorption of sterile water. Absorption of hypotonic irrigant presumably occurred through the injury induced during insertion of the laser cystoscope.

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.

Characterizing TUNA ablative treatments of the prostate for benign hyperplasia with gadolinium-enhanced magnetic resonance imaging.

BACKGROUND AND PURPOSE: Transurethral Needle Ablation of the prostate TUNA has been accepted as an office-based treatment for benign prostatic hyperplasia (BPH) for many years. Clinical outcomes have been reported, but the amount and location of the necrosis produced have yet to be characterized. The necrosis caused by TUNA was evaluated by gadolinium-enhanced magnetic resonance imaging (MRI) of the pelvis. PATIENTS AND METHODS: Twelve patients with BPH/lower urinary-tract symptoms underwent standard TUNA, and MRI scans with gadolinium enhancement were performed before and 1 week after treatment. The images were studied using Analyze software to quantify the amount of necrosis compared with the prostatic volume. Transverse, coronal, and sagittal images were obtained to identify the location of the necrosis. RESULTS: New gadolinium defects were seen in all patients after TUNA. The lesions coalesced into continuous areas of necrosis and correlated with the site of needle placement. The mean volume of necrosis was 6.84 cc and equated to 8.6% of the prostate volume. No lesions were found near the apex, urethra, or rectum; and none extended beyond the prostate capsule. CONCLUSIONS: Gadolinium-enhanced MRI demonstrates new vascular defects representing necrosis caused by TUNA of the prostate. This therapy for BPH produces necrotic lesions that can be placed strategically by the surgeon. The standard protocol produces lesions that coalesce to create larger lesions. This MRI study has characterized, for the first time, the heating pattern and intraprostatic necrosis of a complete TUNA procedure.

Preventing pain during office biopsy of the prostate: a single center, prospective, double-blind, 3-arm, parallel group, randomized clinical trial.

BACKGROUND: A prospective, double-blind, 3-arm, parallel group, randomized clinical trial was performed to compare 3 anesthetic techniques for preventing pain during prostate biopsy. METHODS: A total of 243 men undergoing a 12-core prostate biopsy were randomized to 1 of 3 anesthetic methods: 1) seminal vesical-prostatic base blockade, 2) intraprostatic blockade, and 3) apical-rectal blockade. Pain was estimated with the 10-point visual analog scale. Multivariate logistic regression evaluated factors predictive of pain. The Kruskal-Wallis test analyzed overall group comparisons and the Steel-Dwass test assessed between-group comparisons in pain scores. Proportional odds ordinal logistic regression quantified the ability of covariates and treatment arms to predict biopsy pain. These values are presented as odds ratios with confidence intervals (OR, 95% CI). RESULTS: From November 2005 to June 2006, 81 men were randomized to 3 study arms. Lidocaine administration was the most painful element of the procedure, while probe insertion was the least. Apical biopsies were routinely more painful than mid-gland biopsies, which were more painful than base biopsies. The apical-rectal blockade was the most painful to administer, but has lasting effects and led to better pain control than the prostatic base-seminal vesicle blockade. Similarly, the intraprostatic blockade was more effective than the prostatic base-seminal vesicle blockade. Besides pain reported at the time of anesthetic injection, no difference was identified between the intraprostatic and apical-rectal blockades. CONCLUSIONS: Mid and apical biopsies of the prostate are more painful than base biopsies. The seminal vesicle-prostatic base blockade is less effective than intraprostatic and apical-rectal blockade at controlling pain.

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.