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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms: Systematic review
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Actas Urol Esp. 2015;xxx(xx):xxx---xxx
Actas Urológicas Españolas www.elsevier.es/actasuro
REVIEW ARTICLE
Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms: Systematic review夽 L.M. Sánchez-Gómez a,b,c,∗ , M. Polo-deSantos a , F. Gómez-Sancha d , S. Luengo-Matos a a
Agencia de Evaluación de Tecnologías Sanitarias (AETS), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad, Madrid, Spain b Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa (IP), Madrid, Spain c Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Spain d Instituto de Cirugía Urológica Avanzada, Clínica CEMTRO, Madrid, Spain Received 29 April 2014; accepted 5 May 2014
KEYWORDS Prostate; Urethral lift; Benign prostatic hyperplasia; Minimally invasive surgery; Systematic review
Abstract Context: Interest in having alternatives in the treatment of benign prostate hyperplasia. Objectives: To assess the efficacy and safety of the Urolift® system for treating the symptoms of benign prostate hyperplasia. Acquisition of evidence: Systematic review of the literature through searches on PubMed, Cochrane Library, CRD, Clinical Trials and EuroScan, collecting indicators of efficacy and safety. Summary of the evidence: We included 5 case series and one clinical trial. The patients’ mean age ranged from 65 to 74.3 years, and the mean prostate volume was 41---55 cm3 . The mean number of Urolif® implants was 3.7---5.5. The maximum follow-up in months was 24, 12 (3 studies) and one (2 studies). Improvements were found in lower urinary tract symptoms, as measured with the International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index (BPHII), maximum urinary flow (Qmax ) and postvoid residual (PVR) volume. Improvements were found in sexual dysfunction symptoms, as measured with the Sexual Health Inventory for Men (SHIM) and the Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD), and in quality of life (QoL). In the clinical trial, the differences were significant for International Prostate Symptom Score, BPHII, Qmax and QoL (p < .05). The adverse effects were mild. Conclusions: Although the quality of evidence is low, Urolift® constitutes a good therapeutic alternative for patients with benign prostate hyperplasia. The short- to medium-term results
夽 Please cite this article as: Sánchez-Gómez LM, Polo-deSantos M, Gómez-Sancha F, Luengo-Matos S. Efectividad y seguridad del sistema Urolift® para el tratamiento de los síntomas de la hiperplasia benigna de próstata: revisión sistemática. Actas Urol Esp. 2015. http://dx.doi.org/10.1016/j.acuro.2014.05.010 ∗ Corresponding author. E-mail address: [email protected] (L.M. Sánchez-Gómez).
2173-5786/© 2014 AEU. Published by Elsevier España, S.L.U. All rights reserved.
ACUROE-682; No. of Pages 9
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L.M. Sánchez-Gómez et al. show that the technique contributes to improving lower urinary tract symptoms, with no relevant side effects, and does not affect sexual function and improves quality of life. Further research is required, especially on long-term results. © 2014 AEU. Published by Elsevier España, S.L.U. All rights reserved.
PALABRAS CLAVE Próstata; Lift uretral; Hiperplasia benigna prostática; Cirugía mínimamente invasiva; Revisión sistemática
Efectividad y seguridad del sistema Urolift® para el tratamiento de los síntomas de la hiperplasia benigna de próstata: revisión sistemática Resumen Contexto: Interés por disponer de alternativas en el tratamiento de la hiperplasia benigna de próstata. Objetivo: Evaluar la efectividad y seguridad del sistema Urolift® para el tratamiento de los síntomas de la hiperplasia benigna de próstata. Adquisición de evidencia: Revisión sistemática de la literatura con búsqueda en PubMed, Cochrane Library, CRD, Clinical Trials y EuroScan, recogiéndose indicadores de efectividad y seguridad. Síntesis de evidencia: Se incluyeron 5 series de casos y un ensayo clínico. La edad media de los pacientes osciló entre 65---74,3 a˜ nos, y el volumen prostático medio entre 41-55 cm3 . El ® número medio de implantes Urolif fue de 3,7-5,5. El seguimiento máximo en meses fue de 24, 12 (3 estudios) y uno (2 estudios). Se encontraron mejoras en: síntomas del tracto urinario inferior medidos con International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index (BPHII), flujo urinario máximo (Qmax) y volumen residual postmiccional (PVR); síntomas de función sexual medidos con Sexual Health Inventory for Men (SHIM) y Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD); y calidad de vida (QoL). En el ensayo clínico, las diferencias fueron significativas para International Prostate Symptom Score, BPHII, Qmax y QoL (p < 0,05). Los efectos adversos fueron leves. Conclusiones: Aunque la calidad de la evidencia es baja, Urolift® constituye una buena alternativa terapéutica para pacientes con hiperplasia benigna de próstata. Los resultados a corto/medio plazo muestran que la técnica contribuye a mejorar los síntomas del tracto urinario inferior, sin efectos secundarios relevantes, sin afectar la función sexual y mejorando la calidad de vida. Sería preciso continuar la investigación especialmente sobre resultados a largo plazo. © 2014 AEU. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases in older men and its importance has increased due to population aging. The prevalence increases with age, presenting histological criteria in more than 50% of men over 50 years and in 90% of those over 90 years.1,2 BPH occurs with lower urinary tract symptoms (LUTS) that may be of emptying or storage. Voiding symptoms appear more frequently and respond to a static component by narrowing of the urethral lumen and a dynamic component by altering the tone of the muscle fibers due to enlargement of the prostate.3---5 The prevalence of LUTS in Europe varies with age, with a range that varies from 14% in the fourth decade to more than 40% from the sixth decade, the total prevalence of LUTS being 30%.6 Since BPH and its treatment have a negative impact on quality of life and sexual function,7 the treatment of BPH should be directed to reduce symptoms, improve the quality of life, and prevent the occurrence of complications.2,8---10 There are three treatment options according to the severity of the symptoms: watchful waiting, drug therapy, and surgical treatment.11 Currently, the standard treatment is
transurethral resection of the prostate, although there are other options such as lasers, which while they are less invasive, they involve certain risks like impaired sexual function. Therefore, there is interest in having therapeutic alternatives more efficient than drug therapy without assuming the risks associated with surgical treatment. The Urolift® system emerges as a technology that allows for minimally invasive treatment of LUTS secondary to BPH. It aims to increase the size of the prostatic urethra, retracting the prostate lobes without incisions, surgical resection, or thermal damage on the prostate. The system has two components: a distribution device and permanent implants that keep the prostate lobes retracted and open the urethra.12,13 The technique can be performed under local anesthesia and the operative time is short.12,13 The objective of this review is to evaluate the effectiveness and safety of the Urolift® system for treating the symptoms of BPH.
Material and methods A systematic review of the scientific literature was conducted. The studies were identified by a comprehensive
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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms search of the scientific literature in MEDLINE databases (PubMed), The Cochrane Library, and databases of the CRD (Centre for Reviews and Dissemination, University of York, U.K.). Searches in other databases such as Clinicaltrials and EuroScan were performed. Various search strategies were designed to identify studies using free and controlled terminology combining keywords prostate or prostatic, urethral lift, urolift, and prostatic urethral lifting. We also searched online at web sites of Scientific Societies and Agencies for Health Technology Assessment, of national and international levels. Finally, a manual review of the bibliographic references of the documents found was performed. The study selection was performed until March 3, 2014 unrestricted by date of publication. Any design study, published in English, Spanish or French, with 2 or more BPH patients undergoing treatment of LUTS by the Urolift® system, was included. Duplicate or outdated studies were excluded by subsequent ones at the same institution, narrative reviews, letters to the editor, commentaries, editorials, and studies of a case. As outcome measures, effectiveness indicators were collected: LUTS measured by the International Prostate Symptom Score questionnaire, Benign Prostatic Hyperplasia Impact Index (BPHII), maximum urinary flow (Qmax ), and postvoid residual volume (PVR); symptoms of sexual function measured by the Sexual Health Inventory for Men (SHIM) and Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD); and quality of life measured by QoL. Security indicators were also collected by recording adverse events. Identification, selection and review of studies, as well as data extraction, were performed thoroughly and independently by two reviewers. Disagreements were resolved by consensus or in collaboration with another member of the research team. The quality of evidence was assessed independently by two researchers according to the scale of the Centre for Evidence Based Medicine in Oxford for treatment studies. Tables of evidence of studies that included information on general characteristics of the studies, patient characteristics, and outcome measures in relation to the effectiveness and safety of the procedure were made.
Results A total of 26 articles and 2 documents from the National Institute for Health and Care Excellence (NICE)12,13 were identified. After reading the title and abstract, 3 studies were excluded for not meeting the inclusion criteria. After a thorough reading of the 25 papers that initially met the inclusion/exclusion criteria, 18 publications were excluded11---28 (Table 1), 7 articles29---35 finally being selected, of which 5 were case series29,32---35 and one was a randomized clinical trial (LIFT trial) published in 2 journals with different outcome measures, one for urinary tract symptoms31 and the other one for symptoms of sexual function.30 The flowchart of included and excluded studies is shown in Fig. 1. Case series provide a level of evidence 4 (recommendation grade C) and the LIFT trial has a level of evidence 2B (recommendation grade B) of the scale of the Center for Evidence Based Medicine in Oxford for treatment studies (Table 2).
3
28 Reviewed title and abstract 3 Do not meet inclusión criteria
25 Reviewed full text
2 NICE documents 2 Duplicated articles 2 Articles in German 1 Book of abstracts of a congress 4 Narrative reviews 7 Letters or comments
7 Articles included
5 Case series
Figure 1
2 Publications of 1 randomized clinical trial
Flowchart of the publications included in the study.
The mean age of the patients included ranges from 65 to 74.3 years, with a mean prostate volume that goes from 41 cm3 to 55 cm3 . The type of anesthesia used is different, and it can be local, spinal, or general. The average number of Urolift® implants ranges from 3.7 to 5.5 and the average hospital stay is less than one day. The maximum time of follow-up of studies was 12 months, except for a study with a follow-up of 24 months33 and 2 with a followup of one month.29,35 Table 3 shows the characteristics of the included studies.
Effectiveness results The results for LUTS found in the studies are shown in Table 4: The LIFT trial30,31 shows an improvement of 11 points (50% of improvement) in the IPSS in the group treated with Urolift® (N = 140) vs. an improvement of 5.9 points (24% improvement) in the control group (n = 66) at 3 months of treatment (p = 0.003). The follow-up of 12 months performed only on patients in the group treated with Urolift® shows an improvement of 49%. In the follow-up of 12 months, the studies30---34 found an improvement ranging from 41.8% of improvement34 to 52%.32 One month after the treatment, the percentage of improvement was 45.8%35 and 47.5%.29 For the BPHII, the LIFT trial30,31 describes an improvement of 3.9 points (56% improvement) in the treatment group with Urolift® vs. an improvement of 2.1 points (30% improvement) in the control group at 3 months of treatment (p < 0.001). The follow-up at 12 months performed only on patients in the group treated with Urolift® shows an improvement of 59%. The remaining studies collect a percentage of improvement in the BPHII score ranging from 40.5%34 to 62%.32 Regarding Qmax (ml/s), the LIFT trial improved30,31 has an improvement of 5.40 ml/s (53% improvement) in the treatment group with Urolift® vs. an improvement of 1.98 ml/s
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L.M. Sánchez-Gómez et al. Table 1
Articles excluded and reason for exclusion.
Author
Reference
Reason for exclusion
Without author Arenas da Silva LF Barkin J Berges R Chung A Delongchamps NB Kaplan SA Kaplan SA Larcher A Lusardi L NICE IPG 475 NICE Nickel JC Payton S Roumeguere T Tubaro A Woo H Woo H
Med Lett Drugs Ther 2013; 55(1429): 91 Urologue A 2012; 51(12): 1697---702 Can J Urol 2012; 19(2): 6217---22 Urologue A 2013; 52(3): 350---3 Curr Opin Urol 2014; 24(1): 36---41 Eur Urol 2012; 62(2): 350---1 J Urol 2012; 187(4): 1360 J Urol 2013; 190(4): 1342 Curr Urol Rep 2013; 14(6): 620---7 Curr Opin Urol 2013; 23(1): 25---9 Interventional Procedure Guideline Interventional Procedure overview Rev Urol 2010; 12(2---3): e134---46 Nat Rev Urol 2013; 10(12): 677 Prog Urol 2012; 22(15): 974---5 Eur Urol 2011; 60(5): 1120---1 BJU International 2011; 108(1): 82---8 J Sex Med 2012; 9(2): 568---75
Comment Article in German Review without data Article in German Review without data Letter to the Editor Letter to the Editor Letter to the Editor Review without data Review without data Guideline Review Abstract book Comment Letter to the Editor Letter to the Editor Duplicated study Duplicated study
(24.9% improvement) in the control group at 3 months of treatment (p = 0.005). The follow-up at 12 months performed only on patients in the group treated with Urolift® shows an improvement of 59%. The other studies show a percentage of improvement that ranges from 38%33 to 63.9%.35 The LIFT trial30,31 describes an impovement in PVR of 9.7 ml (11.3% improvement) in the group treated with Urolift® vs. an improvement of 22 ml (26.5% improvement) in the control group at 3 months of treatment (p = 0.306). The follow-up at 12 months made only on patients in the treatment group with Urolift® shows an improvement of 18%. The study by Chin33 shows an improvement of 63% at 24 months of treatment and the one by McNicolas32 an improvement of 3% at 12 months of treatment. The results found for symptoms of sexual function in studies appear in Table 5: The LIFT trial30,31 finds in SHIM/IIEF5 an improvement of 0.1 points (0.75% improvement) in the group treated with Urolift® vs. a 1.5-point improvement (10.9% improvement) in the control group at 3 months of treatment (p = 0.139). The follow-up at 12 months performed only on patients in the treatment group with Urolift® shows an improvement of 2.2%. The study by Chin33 shows an improvement of 7% at
24 months. One month after treatment, an improvement of 23.5%35 and 2.3%29 is described. For MHSQ-EjD (items 1---3), the LIFT trial30,31 describes an improvement of 2.2 points (25.3% improvement) in the group treated with Urolift® versus a 1.7-point improvement (19.3% improvement) in the control group at 3 months of treatment (p = 0.283). The 12-month follow-up conducted to patients in the group treated with Urolift® shows a 14% improvement. The study by Chin33 shows an 11% improvement at 24 months. One month after treatment, 63.6%35 and 18.6% improvement is described.29 For MHSQ-EjD (item 4), the LIFT trial30,31 describes a worsening of 0.8 points (33.3% worsening) in the group treated with Urolift® compared to a worsening of 0.7 points (31.8% worsening) in the control group at 3 months of treatment (p = 0.595). The follow-up at 12 months for patients in the group treated with Urolift® shows a 40% improvement in the MHSQ-EjD4. The study by Shore29 study shows a 56.3% improvement after 1 month of treatment. Neither the study by Chin33 at 24 months of treatment or the study by Delongchamps35 after 1 month of treatment described an improvement in item 4 of the MHSQ-EjD. The results found in studies for QoL are shown in Table 6, the LIFT trial30,31 describing an improvement of 2.2 points
Table 2 Quality of evidence and grade of recommendation according to the scale of the Centre for Evidence Based Medicine at Oxford for treatment studies. Study 33
Chin Delongchamps35 Garrido34 McNicolas32 Shore29 Ensayo LIFT30,31
Design
Level of evidence
Recommendation
CS CS CS CS CS RCT
4 4 4 4 4 2B
C C C C C B
RCT: randomized clinical trial; CS: case series.
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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms Table 3
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General data of included studies.
Study
Design
Number of patients
Mean age (SD) (years)
Prostate volume Mean (SD) (cm3 )
Type of anesthesia (patients)
Mean surgical time (minutes)
Mean number of implants
Mean hospital stay (hours)
Chin33
CS
64
66.9 (7.3)
51 (23)
ND
4
ND
Delongchamps35 CS
4
69
55 (19.1)
11 m
5.5
30 h
Garrido34
CS
20
74.3
42.6
19.1 m
3.8
20.6 h
McNicolas32
CS
102
68 (10)
48 (21)
57.8 m
4.5
ND
Shore29 LIFT30,31
CS RCT
51 206 Urolift® patients: 140 Control: 66
66 (7.6) 67 65
41.3 (11.6) 45 41
Local (26) General (40) General (ND) Spinal (2) Sedation (18) Local (18) Spinal (ND) General (ND) Local (50) Local (169) Spinal (ND) General (ND)
52 m 66.2 m 46.8 m
3.7 4.9
No stay ND
SD: standard deviation; ND: no data; RCT: randomized clinical trial; CS: case series.
(47.8% improvement) in the group treated with Urolift® vs. an improvement of one point (21.2% improvement) in the control group at 3 months of treatment (p < 0.001). The follow-up at 12 months conducted on patients in the group treated with Urolift® shows an improvement in the QoL of 51%. The study by Chin33 shows an improvement in the QoL of 48% at 24 months of treatment, the one by McNicolas32 53% at 12 months of treatment, and the one by Shore29 43.8% after a month of treatment.
Safety results The main adverse effects reported in the studies were dysuria, hematuria, irritative symptoms, urinary retention, Table 4
symptoms of urgency, urinary tract infection, and orchitis. All events were classified as mild and most resolved within 2 weeks after treatment.29---31,33,34 The results found in the studies are listed in Table 7; dysuria is described in the LIFT trial30,31 in 34.3% of patients in the group treated with Urolift® vs. 16.7% in the control group. The study by Garrido34 shows 70% of patients with dysuria, the one by Shore29 73%, and that by McNicolas32 25%. Hematuria was found in the LIFT30,31 trial in 25.7% of patients in the group treated with Urolift® vs. 4.5% in the control group. The study by Garrido34 shows 30% of patients with hematuria, the one by Shore29 78%, and that by McNicolas32 16%. 40% of patients in the study by Garrido34 reported irritative symptoms. Urinary retention is described in the LIFT30,31 trial in 0.7% of patients in the group treated with
Lower urinary tract symptoms. Percentage of improvement after the surgery.
Study
Maximum follow-up time (months)
IPSS/AUASI
BPHII
Qmax
PVR
Chin33 Delongchamps35 Garrido34 McNicolas32 Shore29 LIFT30,31
24 1 12 12 1 3 (RCT: Urolift® vs. control) 12c
42% 45.8% 41.8% 52% 47.5% 50% vs. 24%a 49%
60% ND 40.5% 62% 44.5% 56% vs. 30%a 59%
38% 63.9% 48.3% 51% 47% 53% vs. 24.9%a 59%
63% ND ND 3% ND 11.3% vs. 26.5%b 18%
BPHII: percentage of improvement of the BPH impact index; RCT: randomized clinical trial; IPSS or AUASI: percentage of improvement of the International Prostate Symtom Score or the American Urological Association Symptom Index; PVR: percentage of improvement of the postvoid residual volume; Qmax : percentage of improvement of the maximum urinary flow; ND: no data. a p < 0.05. b p > 0.05. c 12-Month follow-up performed only on patients in the group treated with Urolift® .
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L.M. Sánchez-Gómez et al. Table 5
Sexual function symptoms. Percentage of improvement after the surgery.
Study
Maximum time of follow-up (months)
SHIM/IIEF5
MHSQ-EjD (1---3)
MHSQ-EjD4
Chin33 Delongchamps35 Shore29 LIFT30,31
24 1 1 3 (RCT: Urolift® vs. control) 12b
7% 23.5% 2.3% 0.75% vs. 10.9%a 2.2%
11% 63.6% 18.6% 25.3 vs. 19.3%a 14%
0% 0% 56.3% 33.3% vs. 31.8%a 40%
RCT: randomized clinical trial; MHSQ-EjD (1---3): percentage of improvement of questions 1---3 of the Male Sexual Health Questionnaire for Ejaculatory Dysfunction; MHSQ-EjD4: percentage of improvement of question 4 of the Male Sexual Health Questionnaire for Ejaculatory Disfunction; SHIM or IIEF5: percentage of improvement of the Sexual Health Inventory for Men or the International Index of Erectile Function. a p > 0.05. b 12-Month follow-up performed only on patients in the group treated with Urolift® .
Table 6 Quality of life. Percentage of improvement after the surgery. Study
Maximum follow-up time (months)
QoL
Chin33 Delongchamps35 Garrido34 McNicolas32 Shore29 LIFT30,31
24 1 12 12 1 3 (RCT: Urolift® vs. control) 12b
48% ND ND 53% 43.8% 47.8% vs. 21.2%a 51%
RCT: randomized clinical trial; ND: no data. a p < 0.05. b 12-Month follow-up performed only on patients in the group treated with Urolift® .
Table 7
Urolift® vs. 1.5% in the control group. These symptoms occur in 10% of patients in the study by Garrido34 , in 6% of the study by Shore,29 and in 3% of the study by McNicolas.32 UTIs appear in the LIFT trial30,31 in 3% of patients of the group treated with Urolift® vs. 2% in the control group. The study by Chin33 decribes 12.5% of patients with UTI and the one by McNicolas32 3%. The occurrence of orchitis is described in 5% of patients in the study by Garrido,34 3% in the study by McNicolas,32 and in 1.5% in the study by Chin.33
Discussion The complications associated with surgical treatment and lack of adherence to medical treatment were important stimuli for the search of less invasive therapeutic procedures for patients with BPH.22 The Urolift® system emerges as a new therapeutic alternative that acts mechanically separating the prostatic lobes, thus avoiding the risks associated with surgery.11,34 In this review, we found 6 studies
Percentage of patients with adverse effects.
Estudio Síntomas
Chin33
Delongchamps35
Garrido34
McNicolas32
Shore29
LIFT30,31
Dysuria
Yes.Does not say N.◦
0%
70%
25%
73%
Hematuria
Yes.Does not say N.◦
0%
30%
16%
78%
Urinary retention
ND
0%
10%
3%
6%
Urgency symptoms
ND
ND
ND
10%
8%
Urinary tract infections
12.5%
0%
ND
3%
ND
Irritative symptoms Orchitis Erectile dysfunction Ejaculatory disorders Pelvic pain/discomfort
Yes.Does not say N.◦ 1.5% ND ND ND
0% 0% 0% 0% ND
40% 5% 0% 0% ND
ND 3% ND ND ND
ND ND ND ND 20%
34.3% Urolift® vs. 16.7% control 25.7% Urolift® vs. 4.5% control 0.7% Urolift® vs. 1.5% control 3.6% Urolift® vs. 1.5% control 3% Urolift® vs. 2% control ND 0% 0% 0% 17.9% Urolift® vs. 4.5% control
ND: no data.
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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms evaluating the effectiveness and safety of the Urolift® system for the treatment of symptoms associated with BPH. Of these, only one study is a randomized clinical trial,30,31 and the rest are case series, so we can say that the quality of the evidence found is low. According to some authors,34 patients with a prostate volume between 20 and 50 cm3 are those that offer better responses to treatment with Urolift® . Studies show that patients treated with Urolift® have a mean prostate volume ranging from 41 to 55 cm3 . However, two studies included patients with a mean prostate volume higher than 50 cm3 and show good results after treatment.33,35 Operative time is short, although we found great variability among studies, possibly due to the different way of collecting information, either from the entrance of the patient to the operating room or the treatment time itself. Only two studies report the average hospital stay, and a study points out the absence of hospital stay in the intervention. We believe that given the characteristics and speed of this technology, the average hospital stay is not a variable to consider, as it could be carried out on an outpatient basis. In the LIFT trial,30,31 more than half of the patients were treated with local anesthesia, demonstrating the feasibility of this type of anesthesia to conduct the surgery. The average number of implants or sutures per patient ranges between 3.7 and 5.5 coinciding with what was reported in the scientific literature that maintains that the average number of implants is usually 4.34 Regarding the Urolift® effectiveness, all studies show improvement of LUTS, particularly in subjective scales. Only the LIFT trial at 3 months of follow-up shows that the PVR improves more in the control group than in the group treated with Urolift® . Four studies analyze the results of treatment in relation to sexual function finding improvement of symptoms in the three scales used, but two studies33,35 found no improvement in the MHSQ-EjD4 scale. Regarding the quality of life, we found 4 studies analyzing this variable, although they did not specify the scale used. The studies show a significant improvement, which in the LIFT trial is statistically significant compared to the control group. The NICE documents indicate that some patients may prefer Urolift® treatment to other treatment options with increased risk of sexual dysfunction, and also to long-term drug treatment.12,13 However, this system is indicated only for certain patients, especially patients with mild to moderate symptoms and who wish to preserve sexual function, so it does not seem to get to replace TURP.22 As for the safety of the procedure, studies show that there are no significant side effects associated with this technology. The most common side effect is transient dysuria which occurs in 70% of cases of the study by Garrido.34 However, the symptoms associated with the intervention are mild, easing in most cases in one or two weeks.31,33 Some authors inform that nearly half of the patients do not require catheterization after surgery and among those who need it, in 75% of cases the catheter is removed the day after surgery.33 It is considered that a suitable technique for carrying out the procedure could reduce adverse effects such as dysuria and hematuria and improve the effectiveness of the treatment.16 As the scientific literature points out, no cases of impaired sexual
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function are collected after Urolift® treatment, which is considered one of the most important advantages of the procedure.31,33 Regarding the safety of implants, there have been cystoscopic long-term examinations and the biocompatibility and no incrustation in the prostatic urethra have been checked.31 The follow-up time of patients is short. Only one study33 has follow-up data at two years. The LIFT trial shows comparative data only at 3 months. Therefore, we could say that the effectiveness and safety of the procedure is short/medium term, so far not having long-term results. In the evolution of patients, only some authors collect additional treatments performed in patients treated with Urolift® . Chin et al. found that 20% of patients receive additional treatment in a follow-up period of two years.33 For the time being, the duration of improvement in symptoms is unknown. The NICE documents consider it is likely that this technology does not provide permanent relief of symptoms.12,13 Among the possible limitations of this review we can find, besides the design of the studies, the small number of cases, which is important when evaluating the results. Moreover, some authors do not detail inclusion and exclusion criteria and there is heterogeneity in the studies found. Patients are not homogeneous, there may be differences in the severity of symptoms, or associated drug treatments. Furthermore, although it has not been long since it started being used, the technique has been changing.33 The study by Woo11 describes the evolution of the device and the technique of performing the procedure. According to the authors, the reduction of a 25Fr system to a 20Fr one made it possible to perform the treatment without dilating the urethra, but it probably increased variability in the response. There is also a learning curve in the placement of implants.20 Some authors consider it necessary to perform at least 5 treatments with Urolift® to ensure that the technique of implant placement is optimal.33 In connection with the collection of outcome variables, it is important to highlight the homogeneity in the studies, using recognized and validated LUTS and sexual function scales. However, some authors suggest that patients may be reluctant to answer questions related to sexual function or activity.33 There is agreement in the scientific literature on the positive results of Urolift® treatment and the need to continue research on the procedure. The NICE recommends the research and suggests collecting cases of all patients treated.12,13 According to these documents, it is necessary to pay particular attention to the criteria for selection of patients and evaluate the effectiveness of the procedure on symptoms, quality of life, duration of the benefit (since the long-term results are unknown), and the need of reoperation. Besides, all the complications should be recorded. Currently, there are 2 clinical trials underway with completion scheduled for late 2014 and 2018, respectively and that could provide with new evidence on the Urolift® system,12,13 BPH-6: A UroLift® System PostMarket MultiCenter Randomized Study (NCT01533038) and LOCAL Study: UroLift System TOlerability and ReCovery When Administering Local Anesthesia (NCT01876706).
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8 In this review, we found no economic studies evaluating this technology compared to other alternatives. However, the cost per implant seems to be high, so it would be very interesting to conduct studies of cost-effectiveness. Although the quality of the available evidence is low, we can conclude that the Urolift® system is an interesting therapeutic option for selected patients with symptoms associated with BPH. The available short- and medium-term results show that the technique contributes to the improvement of lower urinary tract symptoms, without relevant side effects, without affecting sexual function, and with an improved quality of life for patients. We consider it essential to continue research on the Urolift® treatment, paying special attention to patient selection criteria to meet those who could most benefit from the technique, and long-term results.
Conflict of interest The authors declare that they have no conflict of interest.
References 1. Auffenberg GB, Helfand BT, McVary KT. Established medical therapy for benign prostatic hiperlasia. Urol Clin North Am. 2009;36:443---59. 2. Osakidetza. Manejo de la hiperplasia benigna de próstata (HBP). Servicio Central de Publicaciones del Gobierno Vasco Boletín Infac, vol. 20 (3); 2012. Available at: http://www.osakidetza. euskadi.net/contenidos/informacion/cevime infac/eu miez/ adjuntos/INFAC Vol 20 n 3.pdf [accessed 13.03.14]. 3. Casajuana Brunet J, Aragonès Forès R. Hiperplasia benigna de próstata. Guía Clínica Fisterra. 2010. Available from: http://www.fisterra.com/fisterrae/guias.asp?idGuia=87 4. Institut Català de la Salut. 3 clics. Atenció primària basada en l’evidència. Hiperplasia benigna de próstata. Institut Català de la Salut; 2008. Available at: http://www.ics.gencat.cat/ 3clics/main.php?page=GuiaPage&idGuia=89 [accessed 13.03.14]. 5. Prósper M, Catalá L, Monedero A, Santamaría J. Hiperplasia benigna de próstata. Guía de Actuación Clínica en A.P. Valencia: Conselleria de Sanitat Generalitat Valenciana; 2011. Available from: http://www.san.gva.es/documents/ 246911/251004/guiasap020prostata.pdf [accessed 13.03.14]. 6. Veiga F, Malfeito R, López C. Hiperplasia benigna de próstata. In: nola de Geriatría y Gerontología, editors. Tratado Sociedad Espa˜ de Geriatría para residentes. Madrid: International Marketing & Communication, SA; 2007. p. 647---53. 7. Castro-Díaz D, Díaz-Cuervo H, Pérez M. Hiperplasia benigna de próstata y su tratamiento: impacto en calidad de vida y función sexual. Actas Urol Esp. 2013;37:233---41. 8. Madersbacher S, Alivizatos G, Nordling J, Rioja C, Emberton M, de la Rosette JJMCH. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower benign prostatic urinarytract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol. 2004;46:547---54. 9. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. Guidelines on the management of male lower urinary tract symptoms (LUTS), incl. Benign prostatic obstruction (BPO). Eur Assoc Urol. 2012. 10. Spatafora S, Conti G, Perachino M, Casarico A, Mazzi G, Pappagallo GL, et al. Evidence-based guidelines for the management of lower urinary tract symptoms related to uncomplicated
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benign prostatic hyperplasia in Italy: updated summary. Curr Med Res Opin. 2007;23:1715---32. Woo HH, Chin PT, McNicholas TA, Gill HS, Plante MK, Bruskewitz RC, et al. Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BJU Int. 2011;108:82---8. National Institute for Health and Care Excellence (NICE). IPG 475. Insertion of prostatic urethral lift implants to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia; 2014. National Institute for Health and Care Excellence (NICE). Interventional Procedure overview of insertion of prostatic urethral lift implants to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia: overview; 2014. A prostatic urethral lift for benign prostatic, hyperplasia. Med Lett Drugs Ther. 2013;55:91, 11. Arenas da Silva LF, Schonthaler M, Cruz F, Gratzke C, Zumbe J, Stenzl A, et al. New treatment strategies for male lower urinary tract symptoms. Urologe A. 2012;51:1697---702. Barkin J, Giddens J, Incze P, Casey R, Richardson S, Gange S. UroLift system for relief of prostate obstruction under local anesthesia. Can J Urol. 2012;19:6217---22. Berges R, Sievert KD, Gratzke C, Wetterauer U. UroLift(R): an operative non-ablative procedure for treatment of benign prostatic syndrome. Urologe A. 2013;52:350---3. Chung A, Woo HH. What’s truly minimally invasive in benign prostatic hyperplasia surgery? Curr Opin Urol. 2014;24:36---41. Delongchamps NB, Zerbib M. Words of wisdom. Re: Prostatic urethral lift: two-year results after treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol. 2012;62:350---1. Re Kaplan SA. Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). J Urol. 2012;187:1360. Kaplan SA. Re: Preservation of sexual function with the prostatic urethral lift: a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2013;190:1342. Larcher A, Broglia L, Lughezzani G, Mistretta F, Abrate A, Lista G, et al. Urethral lift for benign prostatic hyperplasia: a comprehensive review of the literature. Curr Urol Rep. 2013;14: 620---7. Lusuardi L, Hruby S, Janetschek G. New emerging technologies in benign prostatic hyperplasia. Curr Opin Urol. 2013;23:25---9. Nickel JC, Furuta A, Chancellor MB, Roehrborn CG, Assimos DG, Shapiro E, et al. Best of the AUA Annual Meeting: Highlights From the 2010 American Urological Association Meeting, May 29-June 3, 2010, San Francisco, CA. Rev Urol. 2010;12(2---3):e134---46. Payton S. BPH: promising future for the prostatic urethral lift. Nat Rev Urol. 2013;10:677. Roumeguere T. Comment to intra-prostatic UroLift((R)) implants for benign prostatic hyperplasia. Prog Urol. 2012;22:974---5. Tubaro A, De Nunzio C. Words of wisdom. Re: Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Eur Urol. 2011;60: 1120---1. Woo HH, Bolton DM, Laborde E, Jack G, Chin PT, Rashid P, et al. Preservation of sexual function with the prostatic urethral lift: a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med. 2012;9:568---75. Shore N, Freedman S, Gange S, Moseley W, Heron S, Tutrone R, et al. Prospective multi-center study elucidating patient experience after prostatic urethral lift. Can J Urol. 2014;21: 7094---101.
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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms 30. McVary KT, Gange SN, Shore ND, Bolton DM, Cowan BE, Brown BT, et al. Treatment of LUTS secondary to BPH while preserving sexual function: randomized controlled study of prostatic urethral lift. J Sex Med. 2014;11:279---87. 31. Roehrborn CG, Gange SN, Shore ND, Giddens JL, Bolton DM, Cowan BE, et al. The prostatic urethral lift for the treatment of lower urinary tract symptoms associated with prostate enlargement due to benign prostatic hyperplasia: the L.I.F.T. study. J Urol. 2013;190:2161---7. 32. McNicholas TA, Woo HH, Chin PT, Bolton D, Fernandez AM, Sievert KD, et al. Minimally invasive prostatic urethral lift: surgical technique and multinational experience. Eur Urol. 2013;64:292---9.
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33. Chin PT, Bolton DM, Jack G, Rashid P, Thavaseelan J, Yu RJ, et al. Prostatic urethral lift: two-year results after treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Urology. 2012;79:5---11. 34. Garrido AP, Coloma DP, Sinues OB, Fernandez AM. Urolift(R), a new minimally invasive treatment for patients with low urinary tract symptoms secondary to BPH. Preliminary results. Arch Esp Urol. 2013;66:584---91. 35. Delongchamps NB, Conquy S, Defontaines J, Zerbib M, Peyromaure M. Intra-prostatic UroLift ((R)) implants for benign prostatic hyperplasia: preliminary results of the four first cases performed in France. Prog Urol. 2012;22: 590---7.
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Actas Urológicas Españolas www.elsevier.es/actasuro
REVIEW ARTICLE
Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms: Systematic review夽 L.M. Sánchez-Gómez a,b,c,∗ , M. Polo-deSantos a , F. Gómez-Sancha d , S. Luengo-Matos a a
Agencia de Evaluación de Tecnologías Sanitarias (AETS), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad, Madrid, Spain b Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa (IP), Madrid, Spain c Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Spain d Instituto de Cirugía Urológica Avanzada, Clínica CEMTRO, Madrid, Spain Received 29 April 2014; accepted 5 May 2014
KEYWORDS Prostate; Urethral lift; Benign prostatic hyperplasia; Minimally invasive surgery; Systematic review
Abstract Context: Interest in having alternatives in the treatment of benign prostate hyperplasia. Objectives: To assess the efficacy and safety of the Urolift® system for treating the symptoms of benign prostate hyperplasia. Acquisition of evidence: Systematic review of the literature through searches on PubMed, Cochrane Library, CRD, Clinical Trials and EuroScan, collecting indicators of efficacy and safety. Summary of the evidence: We included 5 case series and one clinical trial. The patients’ mean age ranged from 65 to 74.3 years, and the mean prostate volume was 41---55 cm3 . The mean number of Urolif® implants was 3.7---5.5. The maximum follow-up in months was 24, 12 (3 studies) and one (2 studies). Improvements were found in lower urinary tract symptoms, as measured with the International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index (BPHII), maximum urinary flow (Qmax ) and postvoid residual (PVR) volume. Improvements were found in sexual dysfunction symptoms, as measured with the Sexual Health Inventory for Men (SHIM) and the Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD), and in quality of life (QoL). In the clinical trial, the differences were significant for International Prostate Symptom Score, BPHII, Qmax and QoL (p < .05). The adverse effects were mild. Conclusions: Although the quality of evidence is low, Urolift® constitutes a good therapeutic alternative for patients with benign prostate hyperplasia. The short- to medium-term results
夽 Please cite this article as: Sánchez-Gómez LM, Polo-deSantos M, Gómez-Sancha F, Luengo-Matos S. Efectividad y seguridad del sistema Urolift® para el tratamiento de los síntomas de la hiperplasia benigna de próstata: revisión sistemática. Actas Urol Esp. 2015. http://dx.doi.org/10.1016/j.acuro.2014.05.010 ∗ Corresponding author. E-mail address: [email protected] (L.M. Sánchez-Gómez).
2173-5786/© 2014 AEU. Published by Elsevier España, S.L.U. All rights reserved.
ACUROE-682; No. of Pages 9
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L.M. Sánchez-Gómez et al. show that the technique contributes to improving lower urinary tract symptoms, with no relevant side effects, and does not affect sexual function and improves quality of life. Further research is required, especially on long-term results. © 2014 AEU. Published by Elsevier España, S.L.U. All rights reserved.
PALABRAS CLAVE Próstata; Lift uretral; Hiperplasia benigna prostática; Cirugía mínimamente invasiva; Revisión sistemática
Efectividad y seguridad del sistema Urolift® para el tratamiento de los síntomas de la hiperplasia benigna de próstata: revisión sistemática Resumen Contexto: Interés por disponer de alternativas en el tratamiento de la hiperplasia benigna de próstata. Objetivo: Evaluar la efectividad y seguridad del sistema Urolift® para el tratamiento de los síntomas de la hiperplasia benigna de próstata. Adquisición de evidencia: Revisión sistemática de la literatura con búsqueda en PubMed, Cochrane Library, CRD, Clinical Trials y EuroScan, recogiéndose indicadores de efectividad y seguridad. Síntesis de evidencia: Se incluyeron 5 series de casos y un ensayo clínico. La edad media de los pacientes osciló entre 65---74,3 a˜ nos, y el volumen prostático medio entre 41-55 cm3 . El ® número medio de implantes Urolif fue de 3,7-5,5. El seguimiento máximo en meses fue de 24, 12 (3 estudios) y uno (2 estudios). Se encontraron mejoras en: síntomas del tracto urinario inferior medidos con International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index (BPHII), flujo urinario máximo (Qmax) y volumen residual postmiccional (PVR); síntomas de función sexual medidos con Sexual Health Inventory for Men (SHIM) y Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD); y calidad de vida (QoL). En el ensayo clínico, las diferencias fueron significativas para International Prostate Symptom Score, BPHII, Qmax y QoL (p < 0,05). Los efectos adversos fueron leves. Conclusiones: Aunque la calidad de la evidencia es baja, Urolift® constituye una buena alternativa terapéutica para pacientes con hiperplasia benigna de próstata. Los resultados a corto/medio plazo muestran que la técnica contribuye a mejorar los síntomas del tracto urinario inferior, sin efectos secundarios relevantes, sin afectar la función sexual y mejorando la calidad de vida. Sería preciso continuar la investigación especialmente sobre resultados a largo plazo. © 2014 AEU. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
Introduction Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases in older men and its importance has increased due to population aging. The prevalence increases with age, presenting histological criteria in more than 50% of men over 50 years and in 90% of those over 90 years.1,2 BPH occurs with lower urinary tract symptoms (LUTS) that may be of emptying or storage. Voiding symptoms appear more frequently and respond to a static component by narrowing of the urethral lumen and a dynamic component by altering the tone of the muscle fibers due to enlargement of the prostate.3---5 The prevalence of LUTS in Europe varies with age, with a range that varies from 14% in the fourth decade to more than 40% from the sixth decade, the total prevalence of LUTS being 30%.6 Since BPH and its treatment have a negative impact on quality of life and sexual function,7 the treatment of BPH should be directed to reduce symptoms, improve the quality of life, and prevent the occurrence of complications.2,8---10 There are three treatment options according to the severity of the symptoms: watchful waiting, drug therapy, and surgical treatment.11 Currently, the standard treatment is
transurethral resection of the prostate, although there are other options such as lasers, which while they are less invasive, they involve certain risks like impaired sexual function. Therefore, there is interest in having therapeutic alternatives more efficient than drug therapy without assuming the risks associated with surgical treatment. The Urolift® system emerges as a technology that allows for minimally invasive treatment of LUTS secondary to BPH. It aims to increase the size of the prostatic urethra, retracting the prostate lobes without incisions, surgical resection, or thermal damage on the prostate. The system has two components: a distribution device and permanent implants that keep the prostate lobes retracted and open the urethra.12,13 The technique can be performed under local anesthesia and the operative time is short.12,13 The objective of this review is to evaluate the effectiveness and safety of the Urolift® system for treating the symptoms of BPH.
Material and methods A systematic review of the scientific literature was conducted. The studies were identified by a comprehensive
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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms search of the scientific literature in MEDLINE databases (PubMed), The Cochrane Library, and databases of the CRD (Centre for Reviews and Dissemination, University of York, U.K.). Searches in other databases such as Clinicaltrials and EuroScan were performed. Various search strategies were designed to identify studies using free and controlled terminology combining keywords prostate or prostatic, urethral lift, urolift, and prostatic urethral lifting. We also searched online at web sites of Scientific Societies and Agencies for Health Technology Assessment, of national and international levels. Finally, a manual review of the bibliographic references of the documents found was performed. The study selection was performed until March 3, 2014 unrestricted by date of publication. Any design study, published in English, Spanish or French, with 2 or more BPH patients undergoing treatment of LUTS by the Urolift® system, was included. Duplicate or outdated studies were excluded by subsequent ones at the same institution, narrative reviews, letters to the editor, commentaries, editorials, and studies of a case. As outcome measures, effectiveness indicators were collected: LUTS measured by the International Prostate Symptom Score questionnaire, Benign Prostatic Hyperplasia Impact Index (BPHII), maximum urinary flow (Qmax ), and postvoid residual volume (PVR); symptoms of sexual function measured by the Sexual Health Inventory for Men (SHIM) and Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD); and quality of life measured by QoL. Security indicators were also collected by recording adverse events. Identification, selection and review of studies, as well as data extraction, were performed thoroughly and independently by two reviewers. Disagreements were resolved by consensus or in collaboration with another member of the research team. The quality of evidence was assessed independently by two researchers according to the scale of the Centre for Evidence Based Medicine in Oxford for treatment studies. Tables of evidence of studies that included information on general characteristics of the studies, patient characteristics, and outcome measures in relation to the effectiveness and safety of the procedure were made.
Results A total of 26 articles and 2 documents from the National Institute for Health and Care Excellence (NICE)12,13 were identified. After reading the title and abstract, 3 studies were excluded for not meeting the inclusion criteria. After a thorough reading of the 25 papers that initially met the inclusion/exclusion criteria, 18 publications were excluded11---28 (Table 1), 7 articles29---35 finally being selected, of which 5 were case series29,32---35 and one was a randomized clinical trial (LIFT trial) published in 2 journals with different outcome measures, one for urinary tract symptoms31 and the other one for symptoms of sexual function.30 The flowchart of included and excluded studies is shown in Fig. 1. Case series provide a level of evidence 4 (recommendation grade C) and the LIFT trial has a level of evidence 2B (recommendation grade B) of the scale of the Center for Evidence Based Medicine in Oxford for treatment studies (Table 2).
3
28 Reviewed title and abstract 3 Do not meet inclusión criteria
25 Reviewed full text
2 NICE documents 2 Duplicated articles 2 Articles in German 1 Book of abstracts of a congress 4 Narrative reviews 7 Letters or comments
7 Articles included
5 Case series
Figure 1
2 Publications of 1 randomized clinical trial
Flowchart of the publications included in the study.
The mean age of the patients included ranges from 65 to 74.3 years, with a mean prostate volume that goes from 41 cm3 to 55 cm3 . The type of anesthesia used is different, and it can be local, spinal, or general. The average number of Urolift® implants ranges from 3.7 to 5.5 and the average hospital stay is less than one day. The maximum time of follow-up of studies was 12 months, except for a study with a follow-up of 24 months33 and 2 with a followup of one month.29,35 Table 3 shows the characteristics of the included studies.
Effectiveness results The results for LUTS found in the studies are shown in Table 4: The LIFT trial30,31 shows an improvement of 11 points (50% of improvement) in the IPSS in the group treated with Urolift® (N = 140) vs. an improvement of 5.9 points (24% improvement) in the control group (n = 66) at 3 months of treatment (p = 0.003). The follow-up of 12 months performed only on patients in the group treated with Urolift® shows an improvement of 49%. In the follow-up of 12 months, the studies30---34 found an improvement ranging from 41.8% of improvement34 to 52%.32 One month after the treatment, the percentage of improvement was 45.8%35 and 47.5%.29 For the BPHII, the LIFT trial30,31 describes an improvement of 3.9 points (56% improvement) in the treatment group with Urolift® vs. an improvement of 2.1 points (30% improvement) in the control group at 3 months of treatment (p < 0.001). The follow-up at 12 months performed only on patients in the group treated with Urolift® shows an improvement of 59%. The remaining studies collect a percentage of improvement in the BPHII score ranging from 40.5%34 to 62%.32 Regarding Qmax (ml/s), the LIFT trial improved30,31 has an improvement of 5.40 ml/s (53% improvement) in the treatment group with Urolift® vs. an improvement of 1.98 ml/s
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Articles excluded and reason for exclusion.
Author
Reference
Reason for exclusion
Without author Arenas da Silva LF Barkin J Berges R Chung A Delongchamps NB Kaplan SA Kaplan SA Larcher A Lusardi L NICE IPG 475 NICE Nickel JC Payton S Roumeguere T Tubaro A Woo H Woo H
Med Lett Drugs Ther 2013; 55(1429): 91 Urologue A 2012; 51(12): 1697---702 Can J Urol 2012; 19(2): 6217---22 Urologue A 2013; 52(3): 350---3 Curr Opin Urol 2014; 24(1): 36---41 Eur Urol 2012; 62(2): 350---1 J Urol 2012; 187(4): 1360 J Urol 2013; 190(4): 1342 Curr Urol Rep 2013; 14(6): 620---7 Curr Opin Urol 2013; 23(1): 25---9 Interventional Procedure Guideline Interventional Procedure overview Rev Urol 2010; 12(2---3): e134---46 Nat Rev Urol 2013; 10(12): 677 Prog Urol 2012; 22(15): 974---5 Eur Urol 2011; 60(5): 1120---1 BJU International 2011; 108(1): 82---8 J Sex Med 2012; 9(2): 568---75
Comment Article in German Review without data Article in German Review without data Letter to the Editor Letter to the Editor Letter to the Editor Review without data Review without data Guideline Review Abstract book Comment Letter to the Editor Letter to the Editor Duplicated study Duplicated study
(24.9% improvement) in the control group at 3 months of treatment (p = 0.005). The follow-up at 12 months performed only on patients in the group treated with Urolift® shows an improvement of 59%. The other studies show a percentage of improvement that ranges from 38%33 to 63.9%.35 The LIFT trial30,31 describes an impovement in PVR of 9.7 ml (11.3% improvement) in the group treated with Urolift® vs. an improvement of 22 ml (26.5% improvement) in the control group at 3 months of treatment (p = 0.306). The follow-up at 12 months made only on patients in the treatment group with Urolift® shows an improvement of 18%. The study by Chin33 shows an improvement of 63% at 24 months of treatment and the one by McNicolas32 an improvement of 3% at 12 months of treatment. The results found for symptoms of sexual function in studies appear in Table 5: The LIFT trial30,31 finds in SHIM/IIEF5 an improvement of 0.1 points (0.75% improvement) in the group treated with Urolift® vs. a 1.5-point improvement (10.9% improvement) in the control group at 3 months of treatment (p = 0.139). The follow-up at 12 months performed only on patients in the treatment group with Urolift® shows an improvement of 2.2%. The study by Chin33 shows an improvement of 7% at
24 months. One month after treatment, an improvement of 23.5%35 and 2.3%29 is described. For MHSQ-EjD (items 1---3), the LIFT trial30,31 describes an improvement of 2.2 points (25.3% improvement) in the group treated with Urolift® versus a 1.7-point improvement (19.3% improvement) in the control group at 3 months of treatment (p = 0.283). The 12-month follow-up conducted to patients in the group treated with Urolift® shows a 14% improvement. The study by Chin33 shows an 11% improvement at 24 months. One month after treatment, 63.6%35 and 18.6% improvement is described.29 For MHSQ-EjD (item 4), the LIFT trial30,31 describes a worsening of 0.8 points (33.3% worsening) in the group treated with Urolift® compared to a worsening of 0.7 points (31.8% worsening) in the control group at 3 months of treatment (p = 0.595). The follow-up at 12 months for patients in the group treated with Urolift® shows a 40% improvement in the MHSQ-EjD4. The study by Shore29 study shows a 56.3% improvement after 1 month of treatment. Neither the study by Chin33 at 24 months of treatment or the study by Delongchamps35 after 1 month of treatment described an improvement in item 4 of the MHSQ-EjD. The results found in studies for QoL are shown in Table 6, the LIFT trial30,31 describing an improvement of 2.2 points
Table 2 Quality of evidence and grade of recommendation according to the scale of the Centre for Evidence Based Medicine at Oxford for treatment studies. Study 33
Chin Delongchamps35 Garrido34 McNicolas32 Shore29 Ensayo LIFT30,31
Design
Level of evidence
Recommendation
CS CS CS CS CS RCT
4 4 4 4 4 2B
C C C C C B
RCT: randomized clinical trial; CS: case series.
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5
General data of included studies.
Study
Design
Number of patients
Mean age (SD) (years)
Prostate volume Mean (SD) (cm3 )
Type of anesthesia (patients)
Mean surgical time (minutes)
Mean number of implants
Mean hospital stay (hours)
Chin33
CS
64
66.9 (7.3)
51 (23)
ND
4
ND
Delongchamps35 CS
4
69
55 (19.1)
11 m
5.5
30 h
Garrido34
CS
20
74.3
42.6
19.1 m
3.8
20.6 h
McNicolas32
CS
102
68 (10)
48 (21)
57.8 m
4.5
ND
Shore29 LIFT30,31
CS RCT
51 206 Urolift® patients: 140 Control: 66
66 (7.6) 67 65
41.3 (11.6) 45 41
Local (26) General (40) General (ND) Spinal (2) Sedation (18) Local (18) Spinal (ND) General (ND) Local (50) Local (169) Spinal (ND) General (ND)
52 m 66.2 m 46.8 m
3.7 4.9
No stay ND
SD: standard deviation; ND: no data; RCT: randomized clinical trial; CS: case series.
(47.8% improvement) in the group treated with Urolift® vs. an improvement of one point (21.2% improvement) in the control group at 3 months of treatment (p < 0.001). The follow-up at 12 months conducted on patients in the group treated with Urolift® shows an improvement in the QoL of 51%. The study by Chin33 shows an improvement in the QoL of 48% at 24 months of treatment, the one by McNicolas32 53% at 12 months of treatment, and the one by Shore29 43.8% after a month of treatment.
Safety results The main adverse effects reported in the studies were dysuria, hematuria, irritative symptoms, urinary retention, Table 4
symptoms of urgency, urinary tract infection, and orchitis. All events were classified as mild and most resolved within 2 weeks after treatment.29---31,33,34 The results found in the studies are listed in Table 7; dysuria is described in the LIFT trial30,31 in 34.3% of patients in the group treated with Urolift® vs. 16.7% in the control group. The study by Garrido34 shows 70% of patients with dysuria, the one by Shore29 73%, and that by McNicolas32 25%. Hematuria was found in the LIFT30,31 trial in 25.7% of patients in the group treated with Urolift® vs. 4.5% in the control group. The study by Garrido34 shows 30% of patients with hematuria, the one by Shore29 78%, and that by McNicolas32 16%. 40% of patients in the study by Garrido34 reported irritative symptoms. Urinary retention is described in the LIFT30,31 trial in 0.7% of patients in the group treated with
Lower urinary tract symptoms. Percentage of improvement after the surgery.
Study
Maximum follow-up time (months)
IPSS/AUASI
BPHII
Qmax
PVR
Chin33 Delongchamps35 Garrido34 McNicolas32 Shore29 LIFT30,31
24 1 12 12 1 3 (RCT: Urolift® vs. control) 12c
42% 45.8% 41.8% 52% 47.5% 50% vs. 24%a 49%
60% ND 40.5% 62% 44.5% 56% vs. 30%a 59%
38% 63.9% 48.3% 51% 47% 53% vs. 24.9%a 59%
63% ND ND 3% ND 11.3% vs. 26.5%b 18%
BPHII: percentage of improvement of the BPH impact index; RCT: randomized clinical trial; IPSS or AUASI: percentage of improvement of the International Prostate Symtom Score or the American Urological Association Symptom Index; PVR: percentage of improvement of the postvoid residual volume; Qmax : percentage of improvement of the maximum urinary flow; ND: no data. a p < 0.05. b p > 0.05. c 12-Month follow-up performed only on patients in the group treated with Urolift® .
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Sexual function symptoms. Percentage of improvement after the surgery.
Study
Maximum time of follow-up (months)
SHIM/IIEF5
MHSQ-EjD (1---3)
MHSQ-EjD4
Chin33 Delongchamps35 Shore29 LIFT30,31
24 1 1 3 (RCT: Urolift® vs. control) 12b
7% 23.5% 2.3% 0.75% vs. 10.9%a 2.2%
11% 63.6% 18.6% 25.3 vs. 19.3%a 14%
0% 0% 56.3% 33.3% vs. 31.8%a 40%
RCT: randomized clinical trial; MHSQ-EjD (1---3): percentage of improvement of questions 1---3 of the Male Sexual Health Questionnaire for Ejaculatory Dysfunction; MHSQ-EjD4: percentage of improvement of question 4 of the Male Sexual Health Questionnaire for Ejaculatory Disfunction; SHIM or IIEF5: percentage of improvement of the Sexual Health Inventory for Men or the International Index of Erectile Function. a p > 0.05. b 12-Month follow-up performed only on patients in the group treated with Urolift® .
Table 6 Quality of life. Percentage of improvement after the surgery. Study
Maximum follow-up time (months)
QoL
Chin33 Delongchamps35 Garrido34 McNicolas32 Shore29 LIFT30,31
24 1 12 12 1 3 (RCT: Urolift® vs. control) 12b
48% ND ND 53% 43.8% 47.8% vs. 21.2%a 51%
RCT: randomized clinical trial; ND: no data. a p < 0.05. b 12-Month follow-up performed only on patients in the group treated with Urolift® .
Table 7
Urolift® vs. 1.5% in the control group. These symptoms occur in 10% of patients in the study by Garrido34 , in 6% of the study by Shore,29 and in 3% of the study by McNicolas.32 UTIs appear in the LIFT trial30,31 in 3% of patients of the group treated with Urolift® vs. 2% in the control group. The study by Chin33 decribes 12.5% of patients with UTI and the one by McNicolas32 3%. The occurrence of orchitis is described in 5% of patients in the study by Garrido,34 3% in the study by McNicolas,32 and in 1.5% in the study by Chin.33
Discussion The complications associated with surgical treatment and lack of adherence to medical treatment were important stimuli for the search of less invasive therapeutic procedures for patients with BPH.22 The Urolift® system emerges as a new therapeutic alternative that acts mechanically separating the prostatic lobes, thus avoiding the risks associated with surgery.11,34 In this review, we found 6 studies
Percentage of patients with adverse effects.
Estudio Síntomas
Chin33
Delongchamps35
Garrido34
McNicolas32
Shore29
LIFT30,31
Dysuria
Yes.Does not say N.◦
0%
70%
25%
73%
Hematuria
Yes.Does not say N.◦
0%
30%
16%
78%
Urinary retention
ND
0%
10%
3%
6%
Urgency symptoms
ND
ND
ND
10%
8%
Urinary tract infections
12.5%
0%
ND
3%
ND
Irritative symptoms Orchitis Erectile dysfunction Ejaculatory disorders Pelvic pain/discomfort
Yes.Does not say N.◦ 1.5% ND ND ND
0% 0% 0% 0% ND
40% 5% 0% 0% ND
ND 3% ND ND ND
ND ND ND ND 20%
34.3% Urolift® vs. 16.7% control 25.7% Urolift® vs. 4.5% control 0.7% Urolift® vs. 1.5% control 3.6% Urolift® vs. 1.5% control 3% Urolift® vs. 2% control ND 0% 0% 0% 17.9% Urolift® vs. 4.5% control
ND: no data.
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Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms evaluating the effectiveness and safety of the Urolift® system for the treatment of symptoms associated with BPH. Of these, only one study is a randomized clinical trial,30,31 and the rest are case series, so we can say that the quality of the evidence found is low. According to some authors,34 patients with a prostate volume between 20 and 50 cm3 are those that offer better responses to treatment with Urolift® . Studies show that patients treated with Urolift® have a mean prostate volume ranging from 41 to 55 cm3 . However, two studies included patients with a mean prostate volume higher than 50 cm3 and show good results after treatment.33,35 Operative time is short, although we found great variability among studies, possibly due to the different way of collecting information, either from the entrance of the patient to the operating room or the treatment time itself. Only two studies report the average hospital stay, and a study points out the absence of hospital stay in the intervention. We believe that given the characteristics and speed of this technology, the average hospital stay is not a variable to consider, as it could be carried out on an outpatient basis. In the LIFT trial,30,31 more than half of the patients were treated with local anesthesia, demonstrating the feasibility of this type of anesthesia to conduct the surgery. The average number of implants or sutures per patient ranges between 3.7 and 5.5 coinciding with what was reported in the scientific literature that maintains that the average number of implants is usually 4.34 Regarding the Urolift® effectiveness, all studies show improvement of LUTS, particularly in subjective scales. Only the LIFT trial at 3 months of follow-up shows that the PVR improves more in the control group than in the group treated with Urolift® . Four studies analyze the results of treatment in relation to sexual function finding improvement of symptoms in the three scales used, but two studies33,35 found no improvement in the MHSQ-EjD4 scale. Regarding the quality of life, we found 4 studies analyzing this variable, although they did not specify the scale used. The studies show a significant improvement, which in the LIFT trial is statistically significant compared to the control group. The NICE documents indicate that some patients may prefer Urolift® treatment to other treatment options with increased risk of sexual dysfunction, and also to long-term drug treatment.12,13 However, this system is indicated only for certain patients, especially patients with mild to moderate symptoms and who wish to preserve sexual function, so it does not seem to get to replace TURP.22 As for the safety of the procedure, studies show that there are no significant side effects associated with this technology. The most common side effect is transient dysuria which occurs in 70% of cases of the study by Garrido.34 However, the symptoms associated with the intervention are mild, easing in most cases in one or two weeks.31,33 Some authors inform that nearly half of the patients do not require catheterization after surgery and among those who need it, in 75% of cases the catheter is removed the day after surgery.33 It is considered that a suitable technique for carrying out the procedure could reduce adverse effects such as dysuria and hematuria and improve the effectiveness of the treatment.16 As the scientific literature points out, no cases of impaired sexual
7
function are collected after Urolift® treatment, which is considered one of the most important advantages of the procedure.31,33 Regarding the safety of implants, there have been cystoscopic long-term examinations and the biocompatibility and no incrustation in the prostatic urethra have been checked.31 The follow-up time of patients is short. Only one study33 has follow-up data at two years. The LIFT trial shows comparative data only at 3 months. Therefore, we could say that the effectiveness and safety of the procedure is short/medium term, so far not having long-term results. In the evolution of patients, only some authors collect additional treatments performed in patients treated with Urolift® . Chin et al. found that 20% of patients receive additional treatment in a follow-up period of two years.33 For the time being, the duration of improvement in symptoms is unknown. The NICE documents consider it is likely that this technology does not provide permanent relief of symptoms.12,13 Among the possible limitations of this review we can find, besides the design of the studies, the small number of cases, which is important when evaluating the results. Moreover, some authors do not detail inclusion and exclusion criteria and there is heterogeneity in the studies found. Patients are not homogeneous, there may be differences in the severity of symptoms, or associated drug treatments. Furthermore, although it has not been long since it started being used, the technique has been changing.33 The study by Woo11 describes the evolution of the device and the technique of performing the procedure. According to the authors, the reduction of a 25Fr system to a 20Fr one made it possible to perform the treatment without dilating the urethra, but it probably increased variability in the response. There is also a learning curve in the placement of implants.20 Some authors consider it necessary to perform at least 5 treatments with Urolift® to ensure that the technique of implant placement is optimal.33 In connection with the collection of outcome variables, it is important to highlight the homogeneity in the studies, using recognized and validated LUTS and sexual function scales. However, some authors suggest that patients may be reluctant to answer questions related to sexual function or activity.33 There is agreement in the scientific literature on the positive results of Urolift® treatment and the need to continue research on the procedure. The NICE recommends the research and suggests collecting cases of all patients treated.12,13 According to these documents, it is necessary to pay particular attention to the criteria for selection of patients and evaluate the effectiveness of the procedure on symptoms, quality of life, duration of the benefit (since the long-term results are unknown), and the need of reoperation. Besides, all the complications should be recorded. Currently, there are 2 clinical trials underway with completion scheduled for late 2014 and 2018, respectively and that could provide with new evidence on the Urolift® system,12,13 BPH-6: A UroLift® System PostMarket MultiCenter Randomized Study (NCT01533038) and LOCAL Study: UroLift System TOlerability and ReCovery When Administering Local Anesthesia (NCT01876706).
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8 In this review, we found no economic studies evaluating this technology compared to other alternatives. However, the cost per implant seems to be high, so it would be very interesting to conduct studies of cost-effectiveness. Although the quality of the available evidence is low, we can conclude that the Urolift® system is an interesting therapeutic option for selected patients with symptoms associated with BPH. The available short- and medium-term results show that the technique contributes to the improvement of lower urinary tract symptoms, without relevant side effects, without affecting sexual function, and with an improved quality of life for patients. We consider it essential to continue research on the Urolift® treatment, paying special attention to patient selection criteria to meet those who could most benefit from the technique, and long-term results.
Conflict of interest The authors declare that they have no conflict of interest.
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