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Accepted Manuscript
Update on Minimally Invasive Surgery and Benign Prostatic Hyperplasia
Dr Amanda S.J. Chung, Henry H. Woo, Professor
PII: S2214-3882(17)30052-8
DOI: 10.1016/j.ajur.2017.06.001
Reference: AJUR 172
To appear in: Asian Journal of Urology
Received Date: 11 February 2017
Revised Date: 28 February 2017
Accepted Date: 13 March 2017
Please cite this article as: Chung ASJ, Woo HH, Update on Minimally Invasive Surgery and Benign
Prostatic Hyperplasia, Asian Journal of Urology (2017), doi: 10.1016/j.ajur.2017.06.001.
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Review Title: Update on Minimally Invasive Surgery and Benign Prostatic Hyperplasia
Running title: Update on Minimally Invasive Surgery and BPH
Authors;
Dr Amanda S. J. Chung
Eastern Virginia Medical School, Norfolk, VA, USA.
Professor Henry H. Woo
Sydney Adventist Hospital Clinical School, University of Sydney, New South Wales, Australia.
Corresponding author;
Professor Henry Woo
Mailing address: Suite 406, 185 Fox Valley Rd, Wahroonga NSW 2076, Australia
Telephone: +61 2 9473 8765
Fax number: +61-2-9473 8969
Email address: hwoo@urologist.net.au
Received 11th Feb 2017: Received in revised from 28th Feb 2017 Accepted 13th March 2017
KEY WORDS
Prostatic hyperplasia; prostatic diseases; minimally invasive surgical procedures; injections; botulinum
toxin A; ethanol; transurethral resection of prostate; lasers; prostatectomy.
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ABSTRACT:
Transurethral resection of the prostate (TURP) became the gold standard surgical treatment for benign
prostatic obstruction without undergoing randomized controlled trials against the predecessor standard in
open suprapubic prostatectomy. TURP has historically been associated with significant morbidity and this
has fuelled the development of minimally invasive surgical treatment options. Improvements in
perioperative morbidity for TURP has been creating an ever increasing standard that must be met by any
new technologies that are to be compared to this gold standard. Over recent years, there has been the
emergence of novel minimally invasive treatments such as the prostatic urethral lift (PUL; UroLift System),
convective water vapor energy (WAVE; Rezum System), Aquablation (AQUABEAM System), Histotripsy
(Vortx Rx System) and temporary implantable nitinol device (TIND). Intraprostatic injections (NX-1207,
PRX-302, botulinum toxinA, ethanol) have mostly been used with limited efficacy, but may be suitable for
selected patients. This review evaluates these novel minimally invasive surgical options with special
reference to the literature published in the past 5 years.
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Introduction
Minimally invasive surgery for benign prostatic hyperplasia (BPH) is a dynamic field, with novel treatment
modalities emerging in experimental and clinical use with various safety and efficacy profiles. This review
aims to update the readership on minimally invasive surgical treatments for BPH, by assessing relevant
literature published in the past 5 years.
Several reviews on minimally invasive surgical treatments for lower urinary tract symptoms (LUTS) due to
BPH have been published within the last 2 years, perhaps an indication of the interest and progress in
this dynamic field of surgical device technology [1,2]. Transurethralresection of the prostate (TURP) and
open simple prostatectomy (OSP) have been the historical reference-standard procedures for decades.
Although both operations are highly effective and offer durable improvements in urinary functional
outcomes, they are also associated with risk of considerable perioperative complications and morbidity
[3].A number of new technologies are at various stages of experimental and clinical trial ranging from
animal models and early clinical trials through to complete commercialization. A number of these
procedures can be performed as quickly as within minutes, in the office or outpatient setting, or with only
local anesthesia or oral sedation [4].
For the purposes of this review, we have examined minimally invasive procedural treatments for LUTS
due to BPH, as defined by the ability for the procedure to be performed either in an office or outpatient
setting with minimal recovery time and morbidity for the patient. We examined technologies such as the
prostatic urethral lift (PUL, UroLift System), convective water vapor treatment (Rezum System), temporary
implantable nitinoldevice (TIND), aquablation(AQUABEAM System), histotripsy(Vortx Rx System) and
intraprostaticinjections. Traditional or standard cavitating prostate operations such as TURP and laser
prostatectomy have not been included within the scope of this study, nor has robotic simple
prostatectomy been considered within the scope of this review.
PUL
The prostatic urethral lift procedure (PUL) (UroLift System, Neotract, CA, USA) involves the transurethral
placement of small permanent intraprostatic implants (comprising of nitinol, polypropylene, and stainless
steel) to retract the obstructive lateral prostatic lobes away from the prostatic urethral lumen, creating an
anterior channel, hence treating benign prostatic obstruction without tissue destruction. This minimally
invasive treatment has been reported by several studies to improve International Prostate Symptom
Score (IPSS) by over 52%, with a weighted mean improvement of 9.22 to 11.82. In a prospective, sham
controlled, pivotal trial the mean IPSS improvement was 11 points, 88% greater than sham controls. The
procedure has been shown to achieve durable outcomes out to 3 years [5].
One of the most favoured advantages of UroLift, is its ability to treat LUTS due to BPH whilst preserving
sexual function, both erectile and ejaculatory. It is an attractive treatment option for men wanting to avoid
the side effects and complications of long-term drug therapy (αblockers or 5-αreductase inhibitors) and
standard surgical BPH operations [6].
Roehrborn et al [7] published the 3-year results of the L.I.F.T. Study, a multi-centre, randomized, patient
and outcome assessor blinded trial of the PUL in men with bothersome LUTS due to BPH. This study
involved 206 patients at 19 centres in North America and Australia, with IPSS 13, peak flow rate
(Qmax) 12 mL/s, and prostate volume between 30 mLand 80 mL. The improvement in IPSS was 88%
greater in the PUL compared with the sham group at 3 months. At 3 years, the mean total IPSS
improvement was significantly improved by 41.1%, quality of life (QoL) by 48.8%, and Qmax by 53.1%.
There were no de novo cases of sustained ejaculatory or erectile dysfunction and all sexual function
assessments showed average stability or improvement after PUL. Patients recovered quickly post-
operation and were able to return to normal physical activities. Fifteen of the 140 patients originally
randomized to PUL required surgical reintervention for treatment failure within the first 3 years.
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Bozkurt et al [8] reported on 17 patients who underwent treatment with PUL, and reported results out to
12 months. Similar to the results from other studies, PUL was shown to offer rapid improvement in LUTS
and QoL and Qmax. There was a 4.2-point increase in Qmax, a 0.9-point improvement in QoL and a 32%
decrease in postvoid residual urine volume. Sexual function was preserved, with no statistically significant
difference (p> 0.05) in the International Index of Erectile Function (IIEF) and Male Sexual Health
Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) scores [8].
Perera et al [9] performed a systematic review and meta-analysis of symptomatic, functional, and sexual
outcomes following the PUL procedure. At the time of that literature search (May 2014), 10articles
comprising six independent patient cohorts were included for analysis. Pooled estimates from between
452 and 680 patients suggested overall improvement following PUL, including symptoms (large gain;
standardised mean gain range of 1.3 to 1.6, IPSS difference of -7.2 to -8.7 points), maximum flow rate
(3.8 to 4.0 mL/s), and QoL (2.2 to 2.4 points). Sexual function was preserved with a small improvement
estimated at 12 months (standardised mean gain range of 0.3 to 0.4). It was concluded that PUL is a well-
tolerated, minimally invasive therapy for BPH that provides favourable symptom, sexual health, and
functional outcomes during follow-up to 12 months [9].
A prospective, randomized, controlled trial (BPH6 Study) at 10 European centres involving 80 men,
showed that significant symptom relief was achieved in both TURP and PUL treatment arms. However,
PUL was associated with better preservation of ejaculation and quality of recovery compared with TURP
(p< 0.01). The study demonstrated non-inferiority of PUL, and superiority of PUL over TURP in terms of a
composite BPH6 endpoint which incorporated symptom relief, quality of recovery, erectile function
preservation, ejaculatory function preservation, continence preservation, and safety[10]. Although
advantageous in terms of important aspects of QoL and minimal to mild complications, PUL does not
appear to improve IPSS, QoL or Qmax, more than TURP and holmium laser enucleation of the prostate
(HoLEP) [11].
In September 2013, the USFood and Drug Administration approved the UroLift. In September 2015, the
UK National Institute for Clinical and Health Excellence also approved the UroLift as an effective, safe
and cost-effective treatment for use in the UK health system, when implemented in a day-case setting
[6,12]. It has been postulated that even earlier management with PUL may even reduce overall cost for
those patients managed with medication. It was concluded that since PUL achieved rapid LUTS
improvement with low risk of complications, the procedure was a safe and cost-effective option for early
treatment of LUTS due to BPH [5].
The UroLift System Tolerability and ReCovery When Administering Local Anesthesia (LOCAL) Study is
ongoing, to evaluate procedure tolerability and surgical recovery following the PUL procedure when
performed under local anaesthesia. It is estimated to be complete in September 2018 (ClinicalTrials.gov
Identifier: NCT01876706).
A limitation of the clinical application of the UroLift procedure is that it had been recommended for the
treatment of obstructing lateral prostate lobes, but not for obstructing prostatic median lobe. However,
there is currently a study in place to evaluate the safety and effectiveness of using UroLift in patients with
prostatic median lobe enlargement – recruitment is currently in progress, and the estimated study
completion date is February 2018 (ClinicalTrials.gov Identifier: NCT02625545).
Convective Water Vapor Treatment
The Rezum system (NxTheraInc, MN, USA) utilizes convective water vapor energy to ablate prostatic
tissue. This minimally invasive surgical treatment can be performed in an office or hospital setting using
oral pain medication, and is applicable to all prostate zones including the median lobe. It has been shown
to be safe and efficacious in both Phase I and II studies[13,14]. Dixon et al [15] studied safety and
efficacy outcomes of the Rezum System from pilot studies of 65 men, and reported statistically significant
clinical improvements at 1, 3, 6, and 12 months for IPSS (decreasing by 6.8, 13.4, 13.1, and 12.5,
respectively) and Qmax (increasing by 2.0, 4.7, 4.3, and 4.6 mL/s, respectively). At 12 months, there was
a 56% improvement in IPSS (p< 0.001), 61% improvement in QoL and 87% improvement in Qmax (p<
0.001). The procedure was safe with an acceptable side effect profile. Sexual function was maintained,
and the majority of adverse events were of short duration and related to the endoscopic instrumentation.
There was only one case of urinary retention in this study[15].
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A multicentre, randomized, controlled trial (Rezum II Study) using WAVE to treat LUTS due to BPH was
conducted in 197 men aged 50 years, with IPSS 13, Qmax15 mL/s, and prostate size 30 to 80mL.
Patients were randomised in a ratio of 2:1 between thermal therapy with the Rezum System (n=136) and
control (n=61). The primary end-point compared IPSS reduction at 3 months and treatment subjects were
followed for 12 months. WAVE treatment was shown to provide rapid and durable improvements in LUTS
due to BPH whilst preserving erectile and ejaculatory function. WAVE and control IPSS decreased by
11.2 ±7.6 and 4.3 ±6.9, respectively (p< 0.0001). IPSS significantly decreased at 2 weeks post-
operation (from 22 to 18.6, p = 0.0006) and by 50% or greater at 3, 6 and 12 months (p < 0.0001).Qmax
increased by 6.2 mL/s at 3 months and this improvement was sustained to 12 months (p< 0.0001).
Adverse events were mild to moderate and resolved quickly [14]. IIEF and MSHQ-EjD scores were not
different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved
31% over baseline (p = 0.0011). Also, 32% of subjects achieved minimal clinically important differences in
erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile
dysfunction [16]. The2-year results were not published at the time of the writing of this review but are
expected to become available in 2017.
Regarding the action of WAVE technology, an MRI study demonstrated the delivery of convective WAVE
technology created thermal lesions in the prostate tissue, which then underwent near complete resolution
by 3 and 6 months after treatment. This was associated with a one-third reduction in overall prostate and
transition zone volumes [17].
TIND
The TIND (Medi-Tate, Or Akiva, Israel) is a nickel-titanium alloy, or nitinol, device which is placed
transurethrally into the prostatic urethra to exert outward pressure on the obstructive prostatic lobes for 5
days prior to removal. It aims to relief bothersome LUTS due to BPH. The results of the first prospective
in-human clinical trial was reported by Porpiglia et al [18]. Thirty-two patients (age >50 years) with LUTS
due to BPH, IPSS 10, of 12 mL/s, and prostate volume of <60 mL, were treated with TIND. With
patients under light sedation, TIND was implanted within the bladder neck and the prostatic urethra using
a rigid cystoscope; TIND was removed 5 days later in an outpatient setting. Mean patient age was 69.4
years, the mean prostate volume was 29.5 mL (±7.4 standard deviation) and the Qmax was 7.6 mL/s (±
2.2 standard deviation). The median IPSS was 19 (interquartile range 14-23) and QoL score was 3
(interquartile range 3-4). All the implantations were successfully completed without intraoperative
complication. Mean operative time was 5.8 min (standard deviation 2.5) and median postoperative stay
was 1 day (interquartile range 1-2). All but one (96%) of the devices was removed 5 days after
implantation in an outpatient setting. Four (12.5%) complications were recorded: 1 (3.1%) urinary
retention, 1 (3.1%) transient incontinence due to device displacement, 1 (3.1%) prostatic abscess and 1
(3.1%) urinary tract infection. No independent prognostic factor for complications was identified. There
were statistically significant differences in the IPSS, quality of life score and Qmax when comparing pre-
and post-operative results at each time point. After 12 months, the median IPSS was 9 (interquartile
range 7-13), median QoL score 1 (interquartile range 1-2), and mean Qmax 12 mL/s (standard deviation
4.7). The mean improvement in IPSS compared with baseline was 45%, and Qmax 67%. No patients
required medical therapy or surgical procedures for BPH at the time of their last follow-up visit 12 months
post-operatio[18]n.
In conclusion, TIND implantation was demonstrated to be a feasible and safe minimally invasive option
for the treatment of LUTS due to BPH. The functional results are encouraging and the treatment
significantly improved patientsQoL [18]. However, this is the first published in-human prospective clinical
trial and further studies are required to confirm these results and assess durability of the procedure
beyond 12 months. There are several clinical trials regarding the TIND Device, as registered on
ClinicalTrials.gov, including a Phase 1, 2 regarding safety and efficacy of TIND for the treatment of BPH
(ClinicalTrials.gov Identifier: NCT01436877) and a Phase 4 one-arm multi-centre international prospective
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study to assess the efficacy of the TIND Device for the treatment of BPH, which began in October 2014
and is estimated to be completed in August 2018 (Clinical Trials.gov Identifier: NCT02145208).
Aquablation
Aquablation (AQUABEAM System, PROCEPT BioRobotics, CA, USA) is a novel minimally invasive water
ablation therapy combining image guidance and robotics for the removal of prostatic tissue as a treatment
for LUTS due to BPH. Under real-time image-based ultrasonic guidance, AQUABEAMtechnology enables
surgical planning and mapping, to achieve a heat-free resection of the prostate using a high-velocity
saline stream. Aquablation is a relatively automated procedure which shows promise in phase 2studies
with few side effects but requires general anaesthesia [13].
In eightcanine models, Faber et al [19] evaluated the safety and efficacy of aquablation (PROCEPT
Aquablation System) treatment to the prostate. The objective of the high-velocity saline stream was to
selectively ablate prostatic glandular tissue while sparing collagenous structures such as blood vessels
and capsule. After ablation, a laser beam was captured by a low-pressure water jet to produce surface
haemostasis. The extent and depth of ablation was predetermined by endoscopic and transrectal
ultrasound guidance. There was no active bleeding in any of the dogs during or after Aquablation.
Complications included twodogs with infection successfully treated with antibiotics, a false passage
created during catheter placement, and twobladder neck perforations (from mechanical insertion),
oneleading to euthanasia. Histologic evaluation at 6 weeks revealed a normal cellular architecture and full
re-epithelialization of the treatment cavity[19].
Gilling et al [20] reported on the first study of aquablation in humans: a prospective, non-randomised,
single-centre trial. The mean age was 73 (range 59-86) years and prostate size was 54 (range 27-85) mL.
40% (6/15) of men had a large prostatic median lobe. At baseline, the men had moderate to severe
LUTS, with mean IPSS 23 and Qmax 8.4 mL/s. All aquablation treatments were performed under general
anaesthesia, and follow-up was conducted at 1, 3 and 6 months. Mean procedural time was 48 min with
an aquablation treatment time of 8 min. All procedures were able to be completed with no serious or
unexpected adverse events. Ninty-three percent (14/15) of patients had their catheters removed on post-
operative day 1, and most patients went home on the first postoperative day. No serious adverse events
occurred within 30 post-operative days. There were no blood transfusions and no significant changes in
serum sodium. One patient received a repeat procedure within 90 days. There was a statistically
significant improvement in mean IPSS from 23.1 at baseline to 8.6 at 6 months (p< 0.001) and Qmax
from 8.6 mL/s at baseline to 18.6 mL/s at the 6 months (p < 0.001). Mean prostate size decreased by
31% to a mean of 36 mL from 54 mL(p< 0.001). No cases of urinary incontinence or erectile dysfunction
were reported[20].
The preliminary results from this initial study show aquablation of the prostate is technically feasible with a
safety profile comparable to other BPH technologies. The combination of surgical mapping by the
operating surgeon and the high-velocity saline appears to deliver a conformal, quantifiable, and
standardised heat-free ablation of the prostate. Advantages of this technique include reduction in
resection time compared with other endoscopic methods, as well as the potential to preserve sexual
function.(20)
A Phase 3 prospective multicentre randomized blinded study comparing Aquablation using the
AQUABEAM System and TURP for the treatment of LUTS due to BPH is in progress, and plans to follow
patients out to 3 years (ClinicalTrials.gov Identifier: NCT02505919). The study began in September 2015;
estimated completion date is September 2019.
Histotripsy
Histotripsy (Vortx Rx System, HistoSonicsInc, MI, USA) is a nonthermal, noninvasive, pulsed ultrasound
technology that homogenizes tissue within the targeted volume. It was investigated in several animal
studies; in-human trials are currently in progress.
Darnell et al [21] reported on histological changes in the prostate after histotripsy treatment in eightcanine
models. In vivohistotripsy of canine prostate produced a 31% decrease in prostate volume and a limited
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inflammatory and fibrotic response. A narrow (1.5 mm) band of fibrosis around the empty, re-epithelialized
treatment cavity was observed 6 weeks after treatment. In four cases, an overall reduction in collagen
content was measured. Further studies are planned to correlate these histologic findings with alteration in
mechanical tissue properties and explore strategies for treatment of BPH with little resulting fibrosis[21].
There is onein-human prospective single-arm clinical trial on histotripsy in progress, as registered on
clinicaltrials.gov, titled “Safety and Initial Efficacy Study of the Vortx Rx for Treatment of Benign Prostatic
Hyperplasia”. The trial, which started in July 2013 and planned to complete in June 2017, aims to assess
and monitor the performance of the Vortx Rx (HistoSonics’Histotripsy BPH Device) in terms of initial
safety and efficacy when used for the treatment of LUTS due to BPH in men aged 50 years old
(ClinicalTrials.gov Identifier: NCT01896973).
Although this technology has had a number of complications in animal models, it has undergone technical
improvements. The results of the first-in-human studies are being awaited.(13)
Injections
Intra-prostatic injections with a variety of agents have been explored as a treatment of LUTS due to BPH
and appear an attractive treatment proposal as they can be readily performed under local
anaesthesia.(13)
NX-1207 injections
NX1207 (Nymox Corporation, Quebec, Canada) is a drug that is administered by transrectalintraprostatic
injection under ultrasound guidance. The substance leads to prostate volume reduction and symptomatic
improvement. However, patient numbers are still low and currently treatment with NX1207 is still
experimental, although results were interesting in Phase 1 and 2 studies.(22, 23) A Phase 3 study
“Evaluation of Re-Injection of NX-1207 for the Treatment of Benign Prostatic Hyperplasia (BPH)” has
been performed, with primary completion date January 2013 (ClinicalTrials.gov Identifier: NCT01438775).
In November 2014, it was reported that NX1207 had failed to reach its primary endpoints and further
development of NX1207 as a treatment for BPH has been abandoned.
PRX-302 injections
PRX302 (topsalysin; Sophiris Bio Corp, CA, USA), a modified recombinant protein, is an experimental
intraprostatic injectable medication, proposed for the treatment of LUTS due to BPH. Results from the
phase 1 and 2 studies were promising. In the phase 2 study (TRIUMPH-1 Trial), there was statistically
significant (p< 0.05) difference in IPSS and Qmax at 3 months post-treatment with PRX302 compared
with placebo according to results posted on ClinicalTrials.gov (ClinicalTrials.gov Identifier:
NCT00889707). No significant safety problems were reported.(23)
A phase 3 study entitled “Randomized, Double-Blind, Vehicle-Controlled, Multicenter Safety and Efficacy
Study of Intraprostatic PRX302 for LUTS BPH (The PLUS-1 Trial)” is ongoing and aims to evaluate the
safety and efficacy of a single treatment of PRX302 for LUTS due to BPH compared to placebo (Clinical
Trials.gov Identifier: NCT01966614). The estimated completion date was December 2015, and published
results are being anticipated.
Botulinum toxin injections
Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum. It inhibits the release of
acetylcholine and other neurotransmitters from the nerve terminal. Botulinum toxin, specifically toxin type
A (BoNT-A) has been used since the 1970s to reduce the muscular hypercontraction disorders. Since
prostate gland as well as bladder is under the influence of autonomic innervation, theoretically, injection
of BoNT-A into the prostate induces chemo-denervation and modulation of prostate function, thereby
reducing LUTS. Furthermore, BoNT-A has been shown to induce prostate apoptosis, downregulation of
α1A receptors, and reduce contractile function of prostate in animal studies. Open studies of
intraprostaticBoNT-A injection have demonstrated promising results in improving voiding dysfunction,
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however, intraprostaticBoNT-A injection did not perform better than the placebo group in recent
publications of placebo controlled studies.(24)
A systematic review and meta-analysis assessing BoNT-A injection for treatment of LUTS due to BPH
showed no difference in efficacy or procedure-related adverse events compared with placebo. Insufficient
evidence of clinical benefit has been demonstrated and therefore clear recommendations for its use
cannot be made.(25)
By contrast, in a study of 32 men with LUTS due to BPH, 200 IU BoNT-A was injected into 5 points at the
lateral and middle lobes of the prostate under ultrasound guidance. All clinical symptoms and indicators
(IPSS, QoL, Qmax, post-void residual urine) improved at 1 month post-treatment, reached optimal levels
6 months post-treatment, and was durable at 12 months post-treatment. Therefore, in this study,
ultrasound-guided BoNT-A injections were found to be safe and effective in the management of BPH.(26)
A case report of BoNT-A injection into the bladder neck was performed in an elderly man who was in
urinary retention but not medically fit enough for transurethral incision of the prostate (TUIP) or TURP.
The result was satisfying as a minimally invasive, tolerated, and cost-effective approach. The authors of
the case report considered it a promising treatment option, but recognised it may only be effective in
selected patients.(27)
Conclusion
The field of novel minimally invasive technologies for the treatment of LUTS due to BPH is an interesting
and dynamic field, with novel procedures being proposed in various phases of experimental and clinical
trial. Most minimally invasive technologies can be performed in an office or outpatient setting, with
minimal recovery time and morbidity to the patient. The PUL (UroLift System) procedure has
demonstrated consistent good functional results similar to TURP out to 3 years, and with the favorable
advantage of improving LUTS due to BPH whilst simultaneously preserving erectile and ejaculatory
function (unlike TURP). Performance of the WAVE (Rezum System) procedure appear promising with
functional improvement of LUTS due to BPH shown in a randomized controlled trial. The results of the
first-in-man prospective trial of the TIND procedure for treatment of LUTS due to BPH have been
promising. Phase 1, 2 and 4 studies are in progress and further validation of results awaited. Aquablation
(AQUABEAM System) has had favorable results in first-in-man studies, and a phase 3 randomized
controlled trial of Aquablation versus TURP is in progress. Histotripsy (Vortx Rx System) remains
experimental, with mixed results in animal studies;one prospective human trial is in progress.
Intraprostatic injections with PRX-302 showed interesting and somewhat promising results in phase 1 and
2 studies, but these results require validation in phase 3 studies. NX-1207 treatment has been
abandoned due to failure to achieve primary endpoints. BoNT-A intraprostatic injections were not of
benefit over placebo in systematic review and meta-analysis, although some individual studies showed
favorable results. Further validation of the performance of these novel minimally invasive treatment
options for LUTS due to BPH in well-designed studies are desired, in order to evaluate their role (or lack
of such a role) in clinical practice.
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CONFLICTS OF INTEREST:
H Woo reports the following conflicts of interest: Boston Scientific- advisory board, NxThera- investigator,
Neotract- stock.
A Chung has no conflicts of interest to declare.
REFERENCES
1. van Rij S, Gilling P. Recent advances in treatment for benign prostatic hyperplasia. F1000Res.
2015;4.
doi: 10.12688/f1000research.7063.1. eCollection 2015.
2. Aoun F, Marcelis Q, Roumeguere T. Minimally invasive devices for treating lower urinary tract
symptoms in benign prostate hyperplasia: technology update. Res Rep Urol. 2015;7:125-36.
3. Sivarajan G, Borofsky MS, Shah O, Lingeman JE, Lepor H. The Role of Minimally Invasive Surgical
Techniques in the Management of Large-gland Benign Prostatic Hypertrophy. Rev Urol. 2015;17:140-9.
4. Roberts WW. New technologies in benign prostatic hyperplasia management. Curr Opin Urol.
2016;26:254-8.
5. Rukstalis DB. Prostatic urethral lift: a novel approach for managing symptomatic BPH in the
aging man. Can J Urol. 2015;22 Suppl 1:67-74.
6. McNicholas TA. Benign prostatic hyperplasia and new treatment options - a critical appraisal of
the UroLift system. Med Devices (Auckl). 2016;9:115-23.
7. Roehrborn CG, Rukstalis DB, Barkin J, Gange SN, Shore ND, Giddens JL, et al. Three year results
of the prostatic urethral L.I.F.T. study. Can J Urol. 2015;22:7772-82.
8. Bozkurt A, Karabakan M, Keskin E, Hirik E, Balci MB, Nuhoglu B. Prostatic Urethral Lift: A New
Minimally Invasive Treatment for Lower Urinary Tract Symptoms Secondary to Benign Prostatic
Hyperplasia. Urol Int. 2016;96:202-6.
9. Perera M, Roberts MJ, Doi SA, Bolton D. Prostatic urethral lift improves urinary symptoms and
flow while preserving sexual function for men with benign prostatic hyperplasia: a systematic review
and meta-analysis. Eur Urol. 2015;67:704-13.
10. Sonksen J, Barber NJ, Speakman MJ, Berges R, Wetterauer U, Greene D, et al. Prospective,
randomized, multinational study of prostatic urethral lift versus transurethral resection of the prostate:
12-month results from the BPH6 study. Eur Urol. 2015;68:643-52.
11. Ray A, Morgan H, Wilkes A, Carter K, Carolan-Rees G. The Urolift System for the Treatment of
Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A NICE Medical Technology
Guidance. Appl Health Econ Health Policy. 2016.
12. Ray A, Morgan H, Wilkes A, Carter K, Carolan-Rees G. The Urolift System for the Treatment of
Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A NICE Medical Technology
Guidance. Appl Health Econ Health Policy. 2016;14:515-26.
13. Nair SM, Pimentel MA, Gilling PJ. Evolving and investigational therapies for benign prostatic
hyperplasia. Can J Urol. 2015;22 Suppl 1:82-7.
14. McVary KT, Gange SN, Gittelman MC, Goldberg KA, Patel K, Shore ND, et al. 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. J Urol.
2016;195:1529-38.
15. Dixon C, Cedano ER, Pacik D, Vit V, Varga G, Wagrell L, et al. Efficacy and Safety of Rezum System
Water Vapor Treatment for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.
Urology. 2015;86:1042-7.
16. McVary KT, Gange SN, Gittelman MC, Goldberg KA, Patel K, Shore ND, et al. Erectile and
Ejaculatory Function Preserved With Convective Water Vapor Energy Treatment of Lower Urinary Tract
Symptoms Secondary to Benign Prostatic Hyperplasia: Randomized Controlled Study. J Sex Med.
2016;13:924-33.
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17. Mynderse LA, Hanson D, Robb RA, Pacik D, Vit V, Varga G, et al. 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. Urology. 2015;86:122-7.
18. Porpiglia F, Fiori C, Bertolo R, Garrou D, Cattaneo G, Amparore D. Temporary implantable nitinol
device (TIND): a novel, minimally invasive treatment for relief of lower urinary tract symptoms (LUTS)
related to benign prostatic hyperplasia (BPH): feasibility, safety and functional results at 1 year of follow-
up. BJU Int. 2015;116:278-87.
19. Faber K, de Abreu AL, Ramos P, Aljuri N, Mantri S, Gill I, et al. Image-guided robot-assisted
prostate ablation using water jet-hydrodissection: initial study of a novel technology for benign prostatic
hyperplasia. J Endourol. 2015;29:63-9.
20. Gilling P, Reuther R, Kahokehr A, Fraundorfer M. Aquablation - image-guided robot-assisted
waterjet ablation of the prostate: initial clinical experience. BJU Int. 2016;117:923-9.
21. Darnell SE, Hall TL, Tomlins SA, Cheng X, Ives KA, Roberts WW. Histotripsy of the Prostate in a
Canine Model: Characterization of Post-Therapy Inflammation and Fibrosis. J Endourol. 2015;29:810-5.
22. Kunit T, Lusuardi L. An evidence-based review of NX1207 and its potential in the treatment of
benign prostatic hyperplasia. Res Rep Urol. 2014;6:67-70.
23. Ebbing J, Bachmann A. Anesthesia-free procedures for benign prostate obstruction: worth it?
Curr Opin Urol. 2015;25:32-9.
24. Hsu YC, Wang HJ, Chuang YC. Intraprostatic Botulinum Neurotoxin Type A Injection for Benign
Prostatic Hyperplasia-A Spotlight in Reality. Toxins (Basel). 2016;8.
doi: 10.3390/toxins8050126.
25. Shim SR, Cho YJ, Shin IS, Kim JH. Efficacy and safety of botulinum toxin injection for benign
prostatic hyperplasia: a systematic review and meta-analysis. Int Urol Nephrol. 2016;48:19-30.
26. Ding XD, Chen HX, Xiao HQ, Wang W, Ding ZG, Zhang GB, et al. Treatment of Benign Prostatic
Hyperplasia by Ultrasound-Guided Botulinum Toxin Type A Injection. Cell Biochem Biophys.
2015;73:357-9.
27. Alam M, Zgheib J, Dalati MF, El Khoury F. Botulinum Toxin A Injection in the Bladder Neck: A
Promising Treatment for Urinary Retention. Case Rep Urol. 2016;2016:6385276.
doi: 10.1155/2016/6385276.
