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Transurethral high-energy water vapour therapy for benign prostate hyperplasia

Source agency:
Agenas (COTE)
Date of Submission:
07/10/2013
Date of Printing:
30/07/2014
Disclaimer:
This report is work in progress and should not be used for external distribution without permission from the originating agency. Users should be aware that reports are based on information available at the time of research and often on a limited literature search.

Technology, Company & Licensing

Technology name:
Rezum System
Technology - description:
Transurethral resection of the prostate (TURP) is recognised as the gold standard surgical treatment for symptomatic BPH [Campos Pinheiro L, 2012]. Modern TURP is safe and efficient for relieving moderate to intense lower urinary tract symptoms (LUTS): mortality is very low (0.1%), 5- and 10-year reoperation rate is 5.8% and 6% respectively [Wasson JH, 2000], the IPSS (International Prostatic Symptoms Score) decreases by 70-50%, and uroflowmetry (Qmax) increases of 125% [Thomas AW, 2005]. However, up to 20% of patients submitted to TURP are not satisfied with their outcome [Mishriki SF, 2008] and complications and side effects may arise, like need of blood transfusion (2.9%), serious transurethral resection syndrome (1.4%), urinary retention (5.8%), urinary tract infection (3.6%), retrograde ejaculation (more than 75%) and sexual dysfunction with impotence (12%) [Campos Pinheiro L, 2012].
Trying to overcome the complications and side effects related to TURP, a plethora of minimally-invasive procedures have been developed in the last two decades to treat BPH by transurethral access, like the transurethral incision of the prostate (TUIP), the transurethral electrovaporisation (TUVP), the visual laser ablation (VLAP), the transurethral microwave therapy (TUMT), the transurethral needle ablation (TUNA), the holmium laser enucleation of the prostate (HoLEP), and the photoselective vaporisation of the prostate (PVP) [Lee SW, 2013].
Water vapour localised injections have been recently proposed to quickly treat BPH in outpatient or office-based setting [Dixon CM, 2012c]. The therapy uses sterile vapour to deliver thermal energy to the gland and damage the hyperplastic tissue. This HS report focuses on the systems able to provide transurethral high-energy water vapour therapy to BPH patients.
We identified only one system intended to treat BPH by transurethral high-energy water vapour therapy: the Rezum system (manufactured by NxThera, Inc.).
The Rezum system is composed by a sterile water container, a vaporiser, a vapour delivery system and a display [Dixon C, 2013c]. During the procedure, water vapour is released, for a few seconds, directly into the hyperplastic tissue by a narrow sheath similar to a rigid cystoscope, inserted transurethrally. The thermal energy released to the tissues denatures the cell membranes, causing cell death, collapse of the vasculature and denervation of the alpha adrenergic nerves and receptors in the treatment zone. Over time, the denatured tissue should be absorbed by the body's immune system response, determining the reduction in hyperplastic tissue volume and allowing the urethra to expand and restore urine flow [Rezum website]. The complete procedure takes a few minutes.
Company or developer:
NxThera
Reason for database entry:
Prioritised by the Regions.
Technology - stage in early warning process:
Assessment complete
Technology - stage of development:
Investigational - phase III
Licensing, reimbursement and other approval:
The Rezum system received the CE mark in 2013; the clinical use of the Rezum system in the USA is limited to investigational purposes, according to the FDA regulation [Rezum website].
Technology - type(s):
Device
Technology - use(s):
Therapeutic

Patient Indication & Setting

Patient indications:
The transurethral high-energy water vapour therapy is proposed to treat patients with benign prostate hyperplasia (BPH) [Rezum website].
Disease description and associated mortality and morbidity:
Although several epidemiological studies have been conducted over the past 20 years, the prevalence of BPH remains difficult to determine. In the absence of a clinically standardised definition, epidemiological data of BPH in the literature are quite variable, because they are strongly influenced by the variables used to define the disease and by considerable heterogeneity in the sampling methods. Generally the variables considered include: prostate enlargement, the presence of LUTS, the reduction in urinary flow, urodynamic obstruction or hyperplasia diagnosed histologically. There is also a lack of homogeneity between studies in the way BPH is evaluated, clinically and through the method of administration of questionnaires to study populations [De La Rosette J, 2006]. BPH is, however, a process closely related to aging [Chute CG, 1993] whose clinical manifestations are represented by symptoms referable to LUTS that negatively impact on the quality of life of patients [Donovan JL, 1997].
The prevalence of BPH ranges around values between 17% and 37%, depending on the age group. Data from USA are quite similar to data collected across Europe [AUA, 2010]. An analysis by age groups conducted in Italy in 2009 showed an increasing trend with increasing age, with a decrease in the over 85: 0.6% (35-44 years); 4.7 (45-54 years); 20.3 (55-64 years ); 37.5 (65-74 years ); 42.9 (75-84 years); and 37.5 (≥85 years) [SIMG, 2010]. A study of European mortality rate of BPH conducted on the WHO mortality database indicates that at the end of the nineties was 0.35/100,000 inhabitants [Levi F, 2003].
Treatment options have different levels of evidence and therefore different levels of recommendation. Medical management can be based on alpha-1-adrenergic antagonists, 5-alpha-reductase inhibitors, antimuscarinics, herbal therapies, phosphodiesterase-5 inhibitors in monotherapy or combination. Surgical options are several, ranging from open prostatectomy to less invasive approaches like TURP [AURO 2012].
Given the high prevalence, low mortality and low progression, BPH and LUTS represent a socio-economic problem as they strongly affect the quality of life of patients [Coyne KS, Wein AJ, 2009; Coyne KS, Kaplan SA, 2009] and impact on the health care system in a considerable way. In Italy, the economic impact of BPH is relevant and tends to increase with the aging of the population (the population of over 65 years has increased from four million in 2000 to about five and a half million in 2012) [ISTAT 2013].
If proved safe and effective, new minimally-invasive treatments, aimed to reduce procedure time, complications, and side effects associated to the current treatments of BPH, may lead to sensible gains in terms of patient’s benefits and costs reduction.
Number of Patients:
-
Technology - specialities(s):
Renal disease & urology
Technology - setting(s):
Other, General hospital and ambulatory care
Setting - further information:
The transurethral high-energy water vapour therapy by the Rezum system can be provided in an outpatient or in-hospital setting [Rezum website].

Impact

Alternative and/or complementary technology:
Substitution technology
Current Technology:
Transurethral high-energy water vapour therapy is proposed to treat patients with BPH thus the main comparator is the TURP, currently considered the gold standard treatment [Lee SW, 2013].
Given the variability in the evidence base, other minimally-invasive surgical approaches, including TUVP, TUIP, VLAP, TUMT, TUNA, HoLEP, and PVP, as well as Botulinum toxin injections and urethral stenting, should be considered as “competitors” of the technology and not proper comparators.
Health Impact:
The Rezum system aims at reducing procedure time, procedural discomfort, and post-procedure complications associated with medications and other treatments [Rezum website].
Diffusion:
According to the manufacturer’s press releases, targeted, early commercialisation of the Rezum system will start in 2014 in selected European countries [Rezum website]. No details about the launch on the Italian market are available.
Cost, infrastructure and economic consequences:
As the manufacturer NxThera decided not to provide any further information about the technology over what is already reported on the website and by press release, no considerations about the costs can be made. The transurethral high-energy water vapour therapy delivered by the Rezum system is meant as a substitute of the standard surgical treatment (TURP), so any cost analysis should consider the new costs versus the current ones.
There are no relevant issues from a structural point of view. No special plant provisioning is required and Rezum system’s dimensions are compatible with general operational activities.
Using data and information available, no considerations can be made about the organisational aspects of the Rezum therapy in term of skills required, training, learning curve of the operators.
Ethical, social, legal, political and cultural impact:
-

Evidence & Policy

Clinical evidence and safety:
We carried out searches on the EuroScan database (12th November 2013) looking for reports on the transurethral high-energy water vapour therapy for BPH. The search gave no results.
We searched the major databases, MEDLINE (29th October 2013), Embase (29th October 2013), and the Cochrane Library (29th October 2013), looking for studies, published from 2008, in Italian or English, reporting on effectiveness and safety of transurethral high-energy water vapour therapy for BPH in all kinds of patients (humans). Among the resulting 19 citations we selected 6 citations for full-text analysis. All the 6 citations were conference abstracts (Table 1); no full-text studies were identified.
One abstract [Larson TR, 2010] reports the proof-of-concept of the Rezum treatment on a group of patients that received the vapour injections prior to prostatectomy or in an office procedure. Reductions in the IPSS were reported at one week and at one month of follow-up.
The remaining five abstracts were published between 2012 and 2013 by the same group of authors [Dixon CM, 2012a; Dixon CM, 2012b; Dixon CM, 2012c; Dixon CM, 2013a; Dixon CM, 2013b] and are funded by the manufacturer RxThera. The three abstracts published in 2012 [Dixon CM, 2012a; Dixon CM, 2012b; Dixon CM, 2012c] were mainly aimed at assessing the patient tolerability and reporting treatment effects. The two abstracts published in 2013 [Dixon CM, 2013a; Dixon CM, 2013b] refer to the same cohort of 30 patients and report improvements in IPSS, quality of life (QOL); maximal urine flow rate (Qmax) and postvoid residual urine measurement (PVR) at up to 6 months of follow-up.
Economic evaluation:
As the manufacturer NxThera decided not to provide any further information about the technology over what is already reported on the website and by press release, no economic evaluation can be made.
Ongoing research:
We searched in the clinicaltrial.gov database (12th November 2013) using “rezum” and “transurethral high-energy water vapour therapy” as combination of keywords and identified one registered study (NCT01912339). The study is currently recruiting participants to evaluate the safety and efficacy of the Rezum system and assess its effect on urinary symptoms secondary to BPH. This study is a US multicenter, prospective, controlled, randomised single-blinded clinical trial started in July 2013 and aimed to enroll 195 subjects (males, 50 years and older). Subjects will be first randomised in a 2:1 proportion in favor of the Treatment Arm (Rezum). Subjects in the Control arm (rigid cystoscopy) will be allowed to crossover to have the Rezum treatment after the 3-month follow-up examination. Completion is expected in June 2019.
Ongoing or planned HTA:
-
Web link:
http://www.agenas.it/agenas_pdf/HS-16_(en).pdf
References and sources:
Bibliography
AUA - American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (BHP). www.auanet.org/common/pdf/education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf
AURO - Linee Guida su LUTS correlati all’Iperplasia Prostatica Benigna. Linee Guida AURO 2012.
Campos Pinheiro L, Martins Pisco J. Treatment of Benign Prostatic Hyperplasia. Techniques in Vascular & Interventional Radiology. Volume 15, Issue 4, 256-260, December 2012.
Chute CG, Panser LA, Girman CJ, Oesterling JE, Guess HA, Jacobsen SJ, Lieber MM. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol. 1993 Jul;150(1):85-9.
Coyne KS, Wein AJ, Tubaro A, Sexton CC, Thompson CL, Kopp ZS, Aiyer LP. The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS. BJU Int. 2009 Apr;103 Suppl 3:4-11.
Coyne KS, Kaplan SA, Chapple CR, Sexton CC, Kopp ZS, Bush EN, Aiyer LP; EpiLUTS Team.Risk factors and comorbid conditions associated with lower urinary tract symptoms: EpiLUTS. BJU Int. 2009 Apr;103 Suppl 3:24-32.
De La Rosette J, Alivizatos G, Madersbacher S, Rioja Sanz C, Nordling J, Emberton M, Gravas S, Michel MC, Oelke M. Guidelines on Benign Prostatic Hyperplasia. European Association of Urology, 2006.
Dixon CM, Huidobro C, Cedano ER, Hoey M, Larson T. Transurethral high calorie water vapor for BPH the rezumtm system. J. Endourol. 2012; 26:A474. [Dixon CM, 2012c]
Dixon CM, Huidobro C, Cedano ER, Hoey M, Larson T. Preliminary data following treatment with vapor for BPH: The rez(registered trademark)umtm system. J. Endourol. 2012; 26:A270. [Dixon CM, 2012a]
Dixon CM, Huidobro C, Cedano ER, Hoey M, Larson T. Acute effects in the human prostate following treatment with high calorie water vapor (rez(registered trademark)umtm). J. Endourol. 2012; 26:A403. [Dixon CM, 2012b]
Dixon C, Rijo-Cedano E, Pacik D et al. Serial MRI and 3D rendering following treatment of BPH using high energy water vapor therapy and the rezumtm system; Initial results from the first-in-man and rezumtm 1 clinical trials. J. Endourol. 2013; 27:A69. [Dixon CM, 2013a]
Dixon C, Rijo-Cedano E, Pacik D et al. Transurethral high energy water vapor therapy for BPH; Initial clinical results of the first-in-man and Rezum 1 clinical trials using the Rezum system. J. Endourol. 2013; 27:A340-A341. [Dixon CM, 2013b].
Donovan JL, Kay HE, Peters TJ, Abrams P, Coast J, Matos-Ferreira A, Rentzhog L, Bosch JL, Nordling J, Gajewski JB, Barbalias G, Schick E, Silva MM, Nissenkorn I, de la Rosette JJ. Using the ICSOoL to measure the impact of lower urinary tract symptoms on quality of life: evidence from the ICS-'BPH' Study. International Continence Society--Benign Prostatic Hyperplasia. Br J Urol. 1997 Nov;80(5):712-21.
ISTAT - Istituto Nazionale di Statistica http://www.istat.it/it/
Larson TR, Huidobro C, Ramis C, Hoey M. New treatment platform in urology: Preliminary clinical results using transurethral controlled vapor injections in the prostate for benign prostatic hypertrophy. J. Endourol. 2010; 24:A207-A208.
Lee SW, Choi JB, Lee KS, Kim TH, Son H, Jung TY, Oh SJ, Jeong HJ, Bae JH, Lee YS, Kim JC. Transurethral procedures for lower urinary tract symptoms resulting from benign prostatic enlargement: a quality and meta-analysis. Int Neurourol J. 2013 Jun;17(2):59-66.
Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C. Recent trends in mortality from benign prostatic hyperplasia. Prostate 2003;56:207-11.
Lusuardi L, Hruby S, Janetschek G. New emerging technologies in benign prostatic hyperplasia. Curr Opin Urol. 2013 Jan;23(1):25-9.
Mishriki SF, Grimsley SJS, Nabi G, et al. Improved quality of life and enhanced satisfaction after TURP: Prospective 12-year follow-up study. Urology 72:322-328, 2008.
Rezum website by NxThera www.rezum.com (accessed on 13th November 2013).
SIMG - VI Report Health Search http://www.healthsearch.it/documenti/Archivio/Report/VIReport_2009-2010/HS_VReport-2010_HiRes.pdf
Thomas AW, Cannon A, Bartlett E, et al. The natural history of lower urinary tract dysfunction in men: minimum 10-year urodynamic follow up of transurethral resection of prostate for bladder outlet obstruction. J Urol 174:1887-1891, 2005.
Wasson JH, Bubolz TA, Lu-Yao GL, et al. Transurethral resection of the prostate among Medicare beneficiaries: 1984 to 1997. J Urol 164:1212-1215, 2000.
Notes:
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