Compliance with the provisions in this policy may be monitored and addressed
through post payment data analysis and subsequent medical review audits.

**History/Background and/or General Information**

Benign prostatic hyperplasia (BPH) is a histological diagnosis characterized
by an increased number of epithelial and stromal cells in the prostate. It is
common in men over the age of 40, and the incidence increases with age. In the
United States, 8 million men older than 50 years old suffer from BPH. In many
cases BPH is asymptomatic, however, symptoms may occur with prostate
enlargement and compression of the urethra leading to bothersome lower urinary
tract symptoms (LUTS), including voiding symptoms such as hesitancy, weak
stream, straining, prolonged voiding, and storage symptoms (frequency,
urgency, and nocturia). LUTS/BPH can have a significant impact on the quality
of life and can cause serious complications such as infections, bleeding,
calculus formation, urinary retention and decline of renal function when
untreated.1 First line treatment generally consists of treatment with
medications such as alpha blockers, PDE5 Inhibitors, or
finasteride/dutasteride. If treatment with medications is not successful,
surgical options may then be considered. Transurethral resection of the
prostate (TURP) and open simple prostatectomy (OSP) are the standard surgical
treatments for LUTS/BPH and are highly effective and provide improved outcomes
in urinary functions. However, neither TURP nor OSP are without considerable
perioperative complication and morbidity.2 Recently, new minimally invasive
surgeries have emerged as alternatives for the resection of the prostate to
manage LUTS in men with BPH. One such surgery is transurethral waterjet
ablation which is minimally invasive; water based surgical therapy that
combines image guidance and robotics to remove prostatic tissue.3 The system
works by pumping high pressure saline (500 to 8000 pounds per square [PSI])
through a probe nozzle to cut and dissect tissue at predetermined system
parameters.3

**Covered Indications**  
Treatment for LUTS/BPH will be considered reasonable and necessary **ONCE per
lifetime** in patients with:

  1. **All** of the following indications: 
    1. Prostate volume of 30-150 cc transrectal ultrasound (TRUS)4,5
    2. Persistent moderate to severe symptoms despite maximal medical management including **ALL** of the following: 
      1. International Prostate Symptom Score (IPSS) 124
      2. Maximum urinary flow rate (Qmax) of 15 mL/s4 (voided volume greater than 125 cc)
      3. Failure, contraindication or intolerance to at least 3 months of conventional medical therapy for LUTS/BPH (e.g., alpha blocker, PDE5 Inhibitor, finasteride/dutasteride)  
  

  2. Only treatment using an FDA approved/cleared device will be considered reasonable and necessary.

**Limitations**  
Transurethral waterjet ablation of the prostate is not considered reasonable
and necessary for patients with the following:

  1. Body mass index  42kg/m26
  2. Known or suspected prostate cancer (based on NCCN Prostate Cancer Early Detection guidelines7) or a prostate specific antigen (PSA) >10 ng/mL unless the patient has had a negative prostate biopsy within the last 6 months.
  3. Bladder cancer, neurogenic bladder, bladder calculus or clinically significant bladder diverticulum6
  4. Active urinary tract or systemic infection6
  5. Treatment for chronic prostatitis6
  6. Diagnosis of urethral stricture, meatal stenosis, or bladder neck contracture6
  7. Damaged external urinary sphincter6
  8. Known allergy to device materials8
  9. Inability to safely stop anticoagulants or antiplatelet agents preoperatively.8

**Notice:** Services performed for any given diagnosis must meet all of the
indications and limitations stated in this policy, the general requirements
for medical necessity as stated in CMS payment policy manuals, any and all
existing CMS national coverage determinations, and all Medicare payment rules.

The redetermination process may be utilized for consideration of services
performed outside of the reasonable and necessary requirements in this LCD.

**Year 1, Year 2 and Year 3 Outcomes**  
Initial clinical experience was reported in 2016, and the technology obtained
FDA clearance in 2017 after the publication of the WATER trial, a PHASE III
multicenter international, double blind, randomized, non-inferiority study
with 181 subjects comparing Aquablation (116/181) to TURP (65/181).9 Men
45-80 years old with prostate size 30-80 cc (by TRUS), moderate-severe LUTS
(International Prostate Symptom Score (IPSS)  12), and maximum urinary flow
rate (Qmax) <15ml/s were included and stringent exclusion criteria applied.
After randomization, although treatment was by an unblinded research team, a
separate blinded team performed all follow-up. The primary endpoint was the
change in the IPSS at 6 months; scores decreased by 16.9 points and 15.1
points for Aquablation and TURP, respectively (noninferiority p<.0001 and
superiority p=0.1347). The primary safety endpoint was the proportion of
subjects with adverse events, defined as Clavien-Dindo grade 2 or higher or
any grade 1 with persistent disability. The 3-month primary safety endpoint
rate was lower in the Aquablation group than in the TURP group (26% vs 42%, p
= 0.0149). At 2 years, IPSS score improvement was sustained (14.7 in
Aquablation and 14.9 in TURP (p=0.834, 95% CI for difference -2.1 to 2.6)),
and Qmax improvement was large in both groups (11.2 and 8.6 cc/s for
Aquablation and TURP, respectively (p = 0.1880, 95% CI for difference -1.3 to
6.4).10 Two-year reduction in post-void residual (PVR) was 57 and 70 cc for
Aquablation and TURP, respectively (p = 0.3895). Prostate specific antigen
(PSA) decreased significantly in both groups by 1 point (p < 0.01).
Retreatment rates were 4.3% and 1.5% (p = 0.42) in the Aquablation and TURP
groups, respectively. Among the subset of sexually active men without the
condition at baseline, anejaculation was less common after Aquablation (10%
vs. 36%, p=0.0003). When post-Aquablation cautery was avoided rates of
anejaculation were lower (7% vs. 16%, p=0.1774), and this resulted in the
reduced grade 1 persistent events found in the Aquablation group. The authors
hypothesize that Aquablation avoids damage to tissues involved in ejaculation
though precise, image-based targeting, and robotic execution. Limitations of
the study include the risk of performance bias as surgeons were not blinded,
and unknown generalizability to a broader population. Three-year results were
essentially unchanged.4

Gilling PJ et al. (2022) published the 5-year follow-up data for the WATER
study.20 Five-year follow-up revealed IPSS scores improved by 15.1 points in
the Aquablation group and 13.2 points in TURP (p = 0.2764). IPSS reduction
was 3.5 points greater across all follow-up visits in the Aquablation group
compared to the TURP group (p = 0.0123) for men with larger prostates (50mL).
Peak urinary flow rates for Aquablation and TURP improved when compared to
baseline (125% and 89% respectively). 12.3% of patients treated with TURP
required a subsequent intervention compared to 6% of patients treated with
Aquablation, up to 5 years secondary to recurrent LUTS.

A 2019 Cochrane Review based on 1-year WATER trial results, found evidence of
similar results with TURP to be of moderate-certainty related to the urologic
symptom score (IPSS) primary outcome measure. All other metrics were graded
low-certainty (QOL), to very low-certainly (adverse events, retreatments,
erectile function, ejaculatory dysfunction).3 Evidence was downgraded mainly
due to study limitations (performance, reporting, and attrition bias), and
imprecision (confidence intervals that crossed the assumed thresholds of
clinically important differences or few events, or both). For example, both
sexual outcome (erectile and ejaculatory function) results were downgraded 2
levels for a combination of imprecision and study limitations (high risk of
performance and attrition bias). The authors recommend larger, more rigorously
conducted, and transparently reported, studies comparing Aquablation to other
techniques (laser enucleation, prostatic urethral lift, robotic-assisted
simple prostatectomy) for which there is also increasing interest.

In a study by Nguyen DD, Barber N, Bidair M et al.6 The authors looked to
determine if the effectiveness of Aquablation is independent of prostate size
by comparing its outcomes in 2 clinical trials. The first trial that was
conducted was with men whose prostate was between 30 and 80 mL (WATER I) and
the other trial was conducted with men whose prostates were between 80 and 150
mL (WATER II). Water I trial is a prospective, double-blind, multicenter,
international clinical trial comparing the safety and efficacy of Aquablation
and TURP as surgical treatments of LUTS due to BPH in men aged 45-80 years
with a prostate volume between 30 and 80 mL, as measured by TRUS. Patients
were enrolled at 17 centers. One hundred sixteen men participated. The Water
II trial was a prospective, multicenter, international clinical trial of
Aquablation for the surgical treatment of LUTS/BPH in men aged 45-80 years
with a prostate volume between 80 and 150 mL, as measured by TRUS. Patients
were enrolled at 13 US and 3 Canadian sites. One hundred one men participated.
The studies parameters included patients who completed the IPSS. Patients
completed questionnaires such as the Incontinence Severity Index (ISI), the
International Index of Erectile Function (IIEF-5), and the Male Sexual Health
Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD). Patients received
uroflowmetry, PVR measurements and underwent standard laboratory blood
assessment. These questionnaires and measurements were provided at baseline.
PVR and lab test were required postoperatively at 1 and 3 months. Adverse
events were rated by the clinical events committee as possible, probably or
definitely related to the study procedure and were classified using Clavien-
Dindo grade for 3 months after treatment. The inclusion and exclusion criteria
were the same for both studies. The inclusion criteria included patients with
moderate-to severe symptoms indicated by a baseline IPSS of 12 and a maximum
urinary flow rate (Qmax) of <15 mL/s. Exclusion criteria included patients
with a body mass index of 42 kg/m2, a history of prostate or bladder cancer,
neurogenic bladder, bladder calculus or clinically significant bladder
diverticulum, active infection, treatment for chronic prostatitis, diagnosis
of urethral stricture, meatal stenosis or bladder neck contracture, a damaged
external urinary sphincter, stress urinary incontinence, post-void residual
urine volume (PVR) >300 mL or urinary retention. The comparison between the 2
studies revealed the mean operative time for WATER I was 33 minutes and 37
minutes for WATER II. The actual treatment time was 4 minutes (WATER I) and 8
minutes (WATER II). For International Prostate Symptom Score, the mean change
at 12 months averaged 15.1 for WATER I and 17.1 for WATER II (P = 0.605).
Clavien-Dindo grade II events at 3 months mark occurred in 19.8% of WATER I
patients and 34.7% of WATER II patients (P = 0.468).6 The authors conclude
outcomes and effectiveness of Aquablation are comparable and are independent
of prostate size with the expectation that with larger prostates a higher risk
of complication is possible.

In an April 2020 publication of WATER II data in the Canadian J Urol, Desai
et. al.5 report, 2 year safety and effectiveness of the Aquablation procedure
for treatment with men with symptomatic benign prostatic hyperplasia (BPH) and
large volume 80-150 cc prostates. The study provides strong evidence that
Aquablation provides excellent mid-term (2 year) long-term relief of LUTS
related to BPH. The study is notable in that enrolled men (target range 80-150
cc, mean 107 cc, 83% with a large median lobe), a group that typically cannot
undergo TURP were included.

Bach et al (2020) conducted a prospective, multicenter, single-arm, open-label
clinical trial (OPEN WATER) of Aquablation therapy in 5 community-based
sites.21 The study included 178 with the diagnosis of LUTS/BPH, aged 38-88
years with a prostate volume between 20 and 148 mL, as measured by TRUS. At
baseline and at 3- and 12-month follow-up, patients completed the following:
IPSS, Incontinence Severity Index, Pain Intensity Scale, Quality of Recovery
Visual Analog Scale, International Index of Erectile Function (IIEF-15), the
Male Sexual Health Questionnaire (MSHQ-EjD), uroflowmetry, and post-void
residual (PVR) volume measurements. The IPSS decreased from 21.7 at baseline
to 6.4 at the 12-month follow-up (p < 0.0001). The maximum urinary flow rate
increased from 9.9 mL/s at baseline to 20.8 mL/s at month 12 (p < 0.0001). PVR
improved from 108 mL to 47 mL at 3 months and 61 mL at 12 months. Ejaculatory
function was relatively preserved. Prostate volume assessed with transrectal
ultrasound decreased 36% by month 3. The authors concluded that "real-world"
evidence (patients in a non-clinical trial setting) shows that the
Aquablation procedure is safe and effective for the treatment of symptomatic
BPH.

A retrospective review of prospectively collected data by Kasraeian et al
(2020) evaluated the safety and efficacy of Aquablation in a community-based
setting.22 The study included 55 patients treated between July 2018 and
December 2019 with prostate size ranging from 27 to 252 mL in volume (mean of
100 mL). Patient ages ranged from 50 to 84 years. Results demonstrated a
significant improvement in the mean IPSS of 17.2 points (p < 0.0001). By
uroflowmetry, the mean Qmax improved from 7.4 mL/sec at baseline to 20.6
mL/sec postoperatively (p < 0.0001). Patients with prostate volume >100 mL had
similar hospital length of stay, BPH symptom reduction, and Qmax improvement
compared to patients with prostate volume <100 mL.

American Urological Association (AUA) amended guidelines now include
Aquablation, but do not classify it as a minimally invasive surgical treatment
(MIST) since general anesthesia is required. Based on 1-year WATER study
results the AUA, found parity between Aquablation and TURP on IPSS, LUTS, and
QOL scores (Quality of Evidence: Moderate). Their recommendation is:
"Aquablation may be offered to patients with LUTS attributed to BPH provided
prostate volume >30/<80g; however, patients should be informed that long term
evidence of efficacy and retreatment rates remains limited. (Conditional
Recommendation; Evidence Level: Grade C)".11

Canadian Urological Association (CUA) 2018 guidelines also give a "conditional
recommendation based on moderate-quality evidence" that Aquablation may be
offered to men "interested in preserving ejaculatory function, with prostates
<80 cc, with or without a middle lobe".12

A 2018 National Institute for Health and Care Excellence (NICE) systematic
review based on 6-month WATER results concluded the procedure should only be
used with "special arrangements," a defined designation meaning there are
uncertainties about safety and effectiveness.13

In summary, promising short-term, single study, Aquablation results have
resulted in, at best, conditional recommendations in some guidelines (AUA,
CUA, NICE). However, a conditional recommendation with Grade C evidence level
(AUA) which translates to "Balance between Benefits & Risks/Burdens unclear.
Alternative strategies may be equally reasonable. Better evidence likely to
change confidence.", echoing the Cochrane Review recommendation: "any
recommendation for or against the use of Aquablation would be based on only
very low-certainty evidence." However, these guideline recommendations predate
publication of mid-term (3-year) results, which demonstrate persistent outcome
with TURP.4 These studies and recommendations demonstrate the safety and
effectiveness of Aquablation as an option for men aged equal to or less than
80, with moderate to severe LUTS due to benign prostate hyperplasia as
indicated by International Prostate Symptom Score (IPSS) equal to or greater
than 12 and a 30-80 cc prostate. Also, the ability to preserve sexual function
is a major consideration.

Further follow up reports 2 year safety and effectiveness of the Aquablation
procedure for treatment with men with symptomatic benign prostatic hyperplasia
(BPH) and large volume 80-150 cc prostates.

Therefore, based on the 2 and 3 year results, as well as recommendations from
the AUA and CUA, water jet treatment of LUTS/BPH is considered to be medically
reasonable and necessary when performed as outlined in this LCD.