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 inch
[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 medically reasonable and
necessary when performed **ONCE** in patients with the following:

  1. Indications including **ALL** of the following: 
    1. Age 80
    2. Prostate volume of 30-150 cc by transrectal ultrasound (TRUS)4,5
    3. Persistent moderate to severe symptoms despite maximal medical management

including **ALL** of the following:

  1.     1.       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 three 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 medically reasonable and necessary.

**Limitations**

The following are considered not medically 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 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.

**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.
Although treatment was by an unblinded research team, after randomization a
separate blinded team performed all follow-up. The primary endpoint was the
change in the IPSS at six months; scores decreased by 16.9 points for
Aquablation and by 16.1 points for 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 two 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

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 two 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 two 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 three 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 two 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 in 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.

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-year) results, which demonstrate persistent similar 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 in men with symptomatic benign prostatic hyperplasia
(BPH) and large volume 80-150 cc prostates.5

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.