This LCD addresses use of the fluid jet system treatment of lower urinary
tract symptoms attributable to benign prostatic hyperplasia (LUTS/BPH).

**Indications**

Treatment for LUTS/BPH will be considered 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)1,2
    3. Persistent moderate to severe symptoms despite maximal medical management including **ALL** of the following:
      1. International Prostate Symptom Score (IPSS) 121
      2. Maximum urinary flow rate (Qmax) of 15 mL/s (voided volume greater than 125 cc)1
      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 reasonable and necessary.

**Limitations**

The following are considered not reasonable and necessary:

  1. Body mass index  42kg/m2
  2. Known or suspected prostate cancer (based on NCCN Prostate Cancer Early Detection guidelines4) 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 diverticulum3
  4. Active urinary tract or systemic infection5
  5. Treatment for chronic prostatitis3
  6. Diagnosis of urethral stricture, meatal stenosis, or bladder neck contracture3
  7. Damaged external urinary sphincter3
  8. Known allergy to device materials5
  9. Inability to safely stop anticoagulants or antiplatelet agents preoperatively.5

**_Background_**

Benign prostatic hyperplasia (BPH) is a histological diagnosis defined as 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. Many cases are
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).
Serious consequences can develop, including acute urinary retention, recurrent
urinary tract infections, bladder stones and diverticula, hematuria, and renal
insufficiency7. The condition impacts quality of life (QOL) and is a
substantial economic burden with a US estimated annual expenditure over 4
billion dollars8.

Treatment for BPH varies based on symptom severity and ranges from
conservative management (monitoring, lifestyle modifications), to medical
management (alpha-blockers, 5-alpha-reductase inhibitors, antimuscarinic and
beta-3 agonists), and finally surgical treatment in approximately 25% of men
over 50 years old. Transurethral resection of the prostate (TURP) is
considered the gold standard surgical intervention for BPH secondary to small
to medium size prostates (30-80 cc). Interest in alternative surgical options
arises from the complications associated with TURP, including dilutional
hyponatremia (TUP syndrome), sexual dysfunction (erectile dysfunction (6.5%),
anejaculation (>5%) retrograde ejaculation (53-75%)), infection, urethral
strictures, bladder neck stenosis or contracture, and hematuria7,9. The most
common surgical procedure for large prostates (> 80 cc) is simple
prostatectomy, which is effective with a low re-operation rate, but requires
an abdominal approach and has a higher risk of bleeding, longer hospital stay
(5 days), and catheterization times. Laser enucleation with holium (HoLEP) or
thulium (ThuLEP) laser is an option for large prostates and offers shorter
hospital stay and less bleeding, but is technically challenging with limited
use in the United States10.

In recent years, minimally invasive treatment options have emerged with the
main goal to be equally effective to TURP, but with a more favorable safety
and convenience profile. Ideally, this includes the rapid and durable relief
of LUTS without compromise of sexual function, under local anesthesia in an
ambulatory setting, with a short convalescence11. Increasingly, a balance
between symptomatic improvement in LUTS and preservation of sexual function is
expected12.

The only FDA cleared (De Novo classification for the resection and removal of
prostate tissue for the treatment of LUTS resulting from BPH) Fluid Jet
System, is the AquaBeam System (PROCEPT BioRobotics)5. This transurethral
approach uses a high-velocity saline jet and real-time ultrasound imaging with
robotic assistance for targeted removal of prostate parenchyma while ideally
sparing collagenous structures (blood vessels, surgical capsule, bladder
neck). Pre-treatment, transrectal ultrasound (TRUS) maps out the specific
region of the prostate to be resected while limiting resection in key
anatomical areas (bladder neck, vermontanum, ejaculatory ducts, external
urinary sphincter). Although resection limits are automatically computer
generated, the surgeon ultimately defines the area of treatment, and the
resection is then executed automatically via a robotic arm. After completion,
flushed tissue particles can be sent for histological analysis; hemostasis is
achieved using electro-cautery or traction from a 3-way catheter balloon. By
minimizing conductive heat damage to erective nerves, Aquablation has a
theoretical advantage in preserving sexual function. Operative time is
reportedly short (mean 33 minutes)6,8, and trials of novice users report a
short learning curve13. Surgeons rate the procedure to be of similar to less
work than TURP or other open/robotic-assisted procedures10.

**_Primary Evidence_**

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)14,15. 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 six 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). The rate of persistent grade 1 events was lower after Aquablation
(7% vs 25%, p = 0.0004), while the rate of grade 2 and greater events was
similar (20% for Aquablation, 23% for TURP (p = 0.3038)). Safety results
remained consistent at 6 months.

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)16. 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). ,
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 population16. Three-year results were essentially unchanged
providing mid-term data on efficacy and safety.

WATER II was a prospective, uncontrolled, multi-centered international
clinical trial to determine if the Aquablation technique was safe in men with
large prostates (80-150 cc)2,17,18. The mean prostate size was 107mL (range
80-150cc) with a middle lobe in 83%. Mean operative time was 37 minutes, mean
resection time 8 minutes, and average length of hospital stay 1.6 days.
Functional outcomes such as IPSS and Qmax, were similar to those seen in the
Water study. The primary safety endpoint, defined as CD Grade 2 or higher or
any Grade 1 event resulting in persistent disability (e.g., ejaculatory
disorder, erectile dysfunction, or permanent incontinence), at 3 months
occurred in 45.5%, which met the study design goal of less than 65% (P
<0.0001). Ejaculatory dysfunction occurred in 19% of sexually active men.
While no electrocautery was used at time of surgery, 10 patients required
transfusion and five cryptoscopic fulgurations for delayed bleeding. Severe
hemorrhage rate for open simple prostatectomy is reported from 7-29%, but
lower for alternative laser procedures9. The 2-year data (n=86) reported
reoperation rate of 2%2. Complication rates are higher for larger prostates as
they are typically more vascular and difficult to treat and the presence of
middle lobe also makes this technically more difficult. A comparison of 1-year
WATER I and WATER II results were similar except for an expected increase in
the risk of complications in larger prostates (by 3 months, Clavien-Dindo
grade  II events occurred in 19.8% of WATER I patients and 34.7% of WATER II
patients (p = 0.468)). 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
possible3.

A 2019 prospective, single-center, cohort study conducted in Germany evaluated
the applicability of Aquablation to a non-selected patient collective19. 118
consecutive patients with symptomatic BPH were enrolled and followed for 3
months post-procedure. Mean prostate volume at time of enrollment was 64.3 
32ml (range 20-154 ml); the number >80ml was not reported. Aquablation was
successfully performed in all, with 10% experiencing significant bleeding
requiring transfusion (2.5%) or second surgical intervention for bleeding
(3.4%). IPSS, Qmax, and PVR improved significantly post procedure and out to 3
months. The same author also published in 2020 a multi-center trial of
Aquablation procedure performed in commercial setting with prostates ranging
from 20-150ml in volume and reported similar safety and effectiveness
outcomes. The mean IPSS reduction at one year was 15.3 and comparable to the
reduction of 15.1 and 17.0 at one year in WATER and WATERII studies,
respectively. The most common complication reported was post-procedure
bleeding, however large prostate size predisposes to this risk and
modification in technique improved bleeding outcomes in later portion of the
study20.

A 2019 Cochrane Review based on 1-year WATER trial results, found evidence of
parity 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)1. 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. However,
this report was limited to the first 12 months of the WATER1 data7.

A 2019 systematic review reports on functional (IPSS, Qmax, QOL, PVR), sexual
(erectile dysfunction, anejaculation), and safety outcomes21. Nine studies
were examined for a total of 445 patients screened. In addition to WATER I
(1-year) and WATER II, a WATER I cohort analysis22, pooled analysis on WATER I
and II cohorts23, and WATER II subpopulation analysis were included13. The
review reports improved outcomes in all functional outcome criteria for
Aquablation, and statistical non-inferiority to TURP. In terms of safety, in
the trials that compared Aquablation to TURP, outcomes (bleeding, urethral
strictures, urinary retention, UTI, dysuria, bladder spasm, voiding
dysfunction) were similar. Sexual outcomes, available in five papers, appear
promising with International Index of Erectile function (IEEF-5) reduced as
compared to TURP (33% vs. 56% in sub-analysis of WATER I, p=0.025). In two
papers, there were no post-treatment erectile dysfunction13,23, and one paper
reported no difference from baseline 24. Ejaculation rates also show better
maintenance after Aquablation, with lower rates of anejaculation, compared to
TURP. In a population of 92 patients, no significant decrease in Male Sexual
Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) at three months was
reported24. The review was limited by relatively small sample size and follow-
up compared to other standard techniques, extreme heterogeneity in the
description, and even reporting, of many outcomes (especially sexual), and
lack of standardized validated questionnaires. The authors conclude that other
multicenter randomized comparison trials (vs. TURP and laser therapy) with
larger cohorts and longer follow-up are needed.

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, they find parity between Aquablation and TURP on IPSS, LUTS, and QOL
scores (Quality of Evidence: Moderate). Their recommendation: "Aquablation may
be offered to patients with LUTS attributed to BPH provided prostate volume
>30/<80g"25 (Conditional Recommendation; Evidence Level: Grade C)".

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"9.

European Association of Urology (EAU) guidelines states: "The first clinical
experience provides encouraging results, with a low risk of sexual
dysfunction, but further modifications of the AquaBeam system may be
necessary. Longer term follow up would help assess the clinical value of
Aquablation"26. They state Aquablation appears to be as effective as TURP both
subjectively and objectively; however, there are still some concerns about the
best methods of achieving post-treatment hemostasis (Strength of rating 1b)26.

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 effectiveness27.

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 with men with symptomatic benign prostatic hyperplasia
(BPH) and large volume 80-150 cc prostates.

The initial non-coverage policy by NGS predated the publication of mid-term
(3-year) results, which demonstrates persistent outcome parity with TURP.

NGS reconsidered the initial non-coverage decision after the publication of
the WATER I 3-year data, which was released after the draft policy was posted,
and provided sufficient evidence in support of use of the technology for
prostates 30-80 cc range. The use of the technology in prostates between
80-150cc is supported by the WATERII data. There is less clarity on the
benefits in this population, however, given the limited access to laser
treatments for large prostates in the U.S. and the potential for lower
morbidity as compared to the alternative procedure of open prostatectomy, we
will allow expansion to 150 cc conditional on continued positive outcomes in
real world population.

Therefore, NGS considers water jet treatment of LUTS/BPH to be medically
reasonable and necessary when performed as outlined in this LCD.