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 (US), 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 treatment will be considered reasonable and necessary
when performed **ONCE** in patients with the following:

  1. Indications including **ALL** the following: 

  1.     1. Prostate volume of 30-150 cc by transrectal ultrasound (TRUS)4,5
    2. Persistent moderate to severe symptoms despite maximal medical management including **ALL** 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 a Food and Drug Administration (FDA) approved/cleared device will be considered reasonable and necessary.

**Limitations**

The following are considered not reasonable and necessary:

  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 infection8
  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 preoperatively8

**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 (NCDs), 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 points for
Aquablation and 16.1 for TURP, respectively (noninferiority p<0.0001 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 = 0.3894). 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
through 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 Aquablation 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-certainty (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 (IPSS), 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 one hundred seventy-eight men 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 conditional recommendations in some guidelines (AUA, CUA, NICE). 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-
and 5-year results, which demonstrate persistent similar or improved outcomes
when compared to TURP.20 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
(BPH) as indicated by 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-, 3-, and 5-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.