Medical Policy

Policy Num:      07.001.011
Policy Name:    Transurethral Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia 
Policy ID:          [07.001.011]  [Ac / B / M- / P-]  [2.01.49]

Last Review:       July 16, 2024
Next Review:       July 20, 2025
 

Related Policies:

07.001.151 - Prostatic Urethral Lift

Transurethral Water Vapor Thermal Therapy and Transurethral Water Jet Ablation (Aquablation) for Benign Prostatic Hypertrophy

summary

Description

Transurethral water vapor thermal therapy and transurethral waterjet ablation (aquablation) have been investigated as minimally invasive alternatives to transurethral resection of the prostate (TURP), considered the traditional standard treatment for benign prostatic hyperplasia (BPH). Transurethral water vapor thermal therapy uses radiofrequency-generated water vapor (~103°C) thermal energy based on the thermodynamic properties of convective versus conductive heat transfer to ablate prostate tissue. Aquablation cuts tissue by using a pressurized jet of fluid delivered to the prostatic urethra.

Summary of Evidence

For individuals who have benign prostatic hypertrophy (BPH) and lower urinary tract symptoms (LUTS) who receive transurethral water vapor thermal therapy, the evidence includes a single 3-month, sham-controlled, randomized trial of 197 patients with a 5-year uncontrolled follow-up phase and 1 multicenter, prospective, single-arm study. The outcomes of interest are symptoms, functional outcomes, quality of life, and treatment-related morbidity. At 3 months, LUTS improved more in the intervention group compared to the sham procedure. No adverse effects on erectile or ejaculatory function were observed, and improvements were sustained through 5 years of follow-up. The evidence is limited by the small sample size, lack of blinding of longer-term outcomes, and lack of comparison to alternative treatments such as transurethral resection of the prostate (TURP). The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have BPH and LUTS who receive aquablation, the evidence includes a single noninferiority randomized controlled trial (RCT) of aquablation compared to TURP in 187 patients with 5 years of follow-up, and several multicenter, prospective, single-arm studies. The outcomes of interest are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The primary efficacy endpoint in the RCT was the difference between groups in the change in International Prostate Symptom Score (IPSS) at 6 months, and the primary safety endpoint was the development of Clavien-Dindo persistent grade 1, or 2 or higher operative complications at 3 months. At 6 months, mean IPSS decreased from baseline by 16.9 points for aquablation and 15.1 points for TURP (mean difference, 1.8 points; p<.0001 for noninferiority and p=.1347 for superiority). The primary safety endpoint rate was lower in the aquablation group compared to the TURP group (26% vs. 42% ; p=.0149). The rate of grade 2 and greater events was similar in the 2 groups (20% for aquablation and 23% for TURP; p=.3038). Over 5 years, improvements remained similar between groups with no new safety signals. Confidence in these conclusions is reduced due to imprecision of estimates and a lack of additional supportive trials, especially with regard to comparative adverse events. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information

Not applicable.

OBJECTIVE

The objective of this evidence review is to determine if transurethral water vapor thermal therapy and aquablation improve the net health outcome in patients with benign prostatic hyperplasia and lower urinary tract symptoms.

POLICY

Transurethral water vapor thermal therapy is considered investigational as a treatment of benign prostatic hyperplasia.

Transurethral waterjet ablation (aquablation) is considered investigational as a treatment of benign prostatic hyperplasia.

POLICY GUIDELINES

Coding

See the Codes table for details.

BENEFIT APPLICATION

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

BACKGROUND

Benign prostatic hyperplasia (BPH) is a common condition in older men, affecting to some degree 40% of men in their 50s, 70% of those between ages 60 and 69, and almost 80% of those ages 70 and older.^1, BPH is a histologic diagnosis defined as an increase in the total number of stromal and glandular epithelial cells within the transition zone of the prostate gland. In some men, BPH results in prostate enlargement which can, in turn, lead to benign prostate obstruction and bladder outlet obstruction, which are often associated with lower urinary tract symptoms (LUTS) including urinary frequency, urgency, irregular flow, weak stream, straining, and waking up at night to urinate. Lower urinary tract symptoms is the most commonly presenting urological complaint and can have a significant impact on the quality of life.^1,

BPH does not necessarily require treatment. The decision on whether to treat BPH is based on an assessment of the impact of symptoms on quality of life along with the potential side effects of treatment. Options for medical treatment include alpha-1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and phosphodiesterase-5 inhibitors. Medications may be used as monotherapy or in combination.^2,

Patients with persistent symptoms despite medical treatment may be considered for surgical treatment. The traditional standard treatment for BPH is transurethral resection of the prostate. TURP is generally considered the reference standard for comparisons of BPH procedures. Several minimally invasive prostate ablation procedures have also been developed, including transurethral microwave thermotherapy, transurethral needle ablation of the prostate, urethromicroablation phototherapy, and photoselective vaporization of the prostate. The prostatic urethral lift procedure involves the insertion of one or more permanent implants into the prostate, which retracts prostatic tissue and maintains an expanded urethral lumen.

Transurethral water vapor thermal therapy and aquablation have been investigated as minimally invasive alternatives to transurethral resection of the prostate. Transurethral water vapor thermal therapy uses radiofrequency-generated water vapor (~103°C) thermal energy based on the thermodynamic properties of convective vs conductive heat transfer to ablate prostate tissue.^3,Aquablation cuts tissue by using a pressurized jet of fluid delivered to the prostatic urethra.

Regulatory Status

In September 2016, the Rezum™ System (NxThera, Inc, acquired by Boston Scientific in 2018) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process (K150786). The FDA determined that this device was substantially equivalent to existing devices (Medtronic Prostiva devices). Rezum is intended to relieve symptoms, obstructions, and reduce prostate tissue associated with benign prostatic hyperplasia. It is indicated for men > 50 years of age with a prostate volume >30cm³ and <80cm³. The Rezum System is also indicated for the treatment of prostate with hyperplasia of the central zone and/or a median lobe.

In April 2017, the Aquabeam^® System (Procept Robotics Corporation) was cleared for marketing by the FDA through the 513(f)(2) (de novo) classification process (DEN170024).^4, The device is intended for the resection and removal of prostate tissue in males with LUTS due to BP, based on WATER trial.

RATIONALE

This evidence review was created in November 2001 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through April 17, 2024.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1

Transurethral Water Vapor Thermal Therapy

Clinical Context and Therapy Purpose

The purpose of transurethral water vapor thermal therapy in patients who have BPH and LUTS is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is men with BPH and LUTS.

Symptoms include urinary frequency, urgency, irregular flow, weak stream, straining and getting up at night to urinate.

Interventions

The therapy being considered is transurethral water vapor thermal therapy.

This procedure involves the transurethral injection of steam into the prostate. Once injected, the steam condenses to water, imparting convective energy to the tissue, causing cell death and damage. The technology uses radiofrequency to boil the water to create the steam that is injected but does not impart radiofrequency directly to the prostate tissue. Patients typically require catheterization for at least one week due to post-procedure sloughing of prostatic tissue.

Medical management of pain and anxiety may also be required. In an RCT, 69% of patients received oral sedation only, 21% received a prostate block, and 10% received intravenous sedation.

Comparators

The following practices and therapies are currently being used to make decisions about transurethral water vapor thermal therapy.

• Conservative treatment, including watchful waiting and lifestyle modifications

• Pharmacotherapy

• TURP

• Prostatic urethral lift

Outcomes

The general outcomes of interest are symptoms, functional outcomes, quality of life, retreatment rates, and treatment-related morbidity.

The International Prostate Symptom Score (IPSS) is used to assess the severity of BPH symptoms. The first seven questions address urinary frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency each on a scale of 0 to 5. The total score, summed across the 7 items measured, ranges from 0 (no symptoms) to 35 (most severe symptoms). A decrease in score indicates improvement.

Quality of life is assessed with various scales including the IPSS-QoL.

Erectile and ejaculatory function is assessed in sexually active men only. Scales include the International Index of Erectile Function and the Mase Sexual Health Questionnaire.

Both short-term (up to 12 months) and long-term (12 months and longer) outcomes should be assessed. Treatment-related morbidity can also be assessed in the immediate post-procedure period.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Review of Evidence

Systematic Review

Kang et al (2020) conducted a Cochrane review of transurethral water vapor thermal therapy for management of LUTS in men with BPH.^5, In literature searches conducted through February 2020, the reviewers identified only one RCT (McVary et al [2015],^6, discussed in the section below). The reviewers concluded that there was moderate-to low-certainty evidence that the procedure appears to improve urologic symptom scores and quality of life compared to a sham procedure. However, there was very low certainty of evidence about the effects of the intervention on major adverse events.

Randomized Controlled Trial

Transurethral water vapor thermal therapy has been evaluated in a single RCT conducted in 197 men (Table 1). Three-month results were reported in McVary et al (2015).^6,

The trial also had an uncontrolled, open-label, crossover phase. After unblinding at 3 months, control subjects who elected to proceed were requalified for the crossover study. A total of 97 patients were followed through 3 years and 90 patients through 4 years. Three-year results were reported in McVary et al (2018)^3,, and 4-year results in McVary et al (2019).^7, These results are shown in Table 1.

Table 1. Randomized Controlled Trial of Rezum: Characteristics

BPH: benign prostatic hyperplasia.

PSS: International Prostate Symptom Score; NCT: national clinical trial; Qmax: maximum urinary flow rate. 

Results of the RCT are shown in Table 2. The primary outcome was the difference in the change from baseline between the treatment and control arms at 3 months post-treatment. The secondary outcome was the percentage of responders at 3 months. Response was defined as a 30% or greater improvement (reduction) in the IPSS at 3 months compared to baseline. The Rezum group showed an 11.2-point decrease in IPSS, versus a 4.3-point decrease in the sham group (p<0.001). There were more responders (defined as 30% or more improvement in the IPSS) in the Rezum group. Notably, more than half of the patients in the control group were classified as responders at 3 months. There were significant differences in other measures of LUTS and quality of life.

One hundred thirty of the 197 participants (70.0%) reported being sexually active at baseline and were assessed for erectile function. There were no significant changes in erectile or ejaculatory function at follow-up and no differences between groups. That is, the treatment was not associated with adverse effects on erectile or ejaculatory function. A post hoc subgroup analysis of 125 Rezum-treated subjects who were sexually active at baseline found that sexual function continued to be unimpacted at 5 years.^8, However, only 67 of these participants (53.6%) had follow-up data at this timepoint.

Two patients in the Rezum group experienced 3 serious procedure-related adverse events: 1 patient had de novo extended urinary retention and another had nausea and vomiting due to alprazolam and was hospitalized overnight for observation.

Table 2. Randomized Controlled Trial of Rezum: Results

AE: adverse events; BPHII: benign prostatic hyperplasia Impact Index; IIEF: International Index of Erectile Function; IPSS: International Prostate Symptom Score; MSHQ-EjD: Male Sexual Health Questionnaire for Ejaculatory Dysfunction; NR: not reported; Qmax: peak urinary flow rate; QoL: quality of life.

The trial also had an uncontrolled, open-label, crossover phase, reported in McVary et al (2018), McVary et al (2019), and McVary et al (2021). After unblinding at 3 months, control subjects who elected to proceed were requalified for the crossover study. A total of 98 patients were followed through 60 months. These results are shown in Table 3. Urinary symptoms and quality of life remained significantly improved from baseline up to 5 years. Over 5 years, the surgical retreatment rate was 4.4% and the medication retreatment rate was 11.1%.^9,

Table 3. Randomized Controlled Trial of Rezum: Results of Open-label Uncontrolled Crossover Phase (McVary et al [2018]^3,, McVary et al [2019]^7,, and McVary et al [2021])^8,

1Some outcomes were presented graphically only and did not include number analyzed, P-values, or change from baseline.BPHII: Benign Prostatic Hyperplasia Impact Index; IIEF-EF: International Index of Erectile Function; IPSS: International Prostate Symptom Score; MSHQ-EjD: Male Sexual Health Questionnaire for Ejaculatory Dysfunction; NR: not reported; PVR: postvoid residual urine volume; Qmax: peak urinary flow rate; QoL: quality of life; SD: standard deviation.

Notable relevance and study design and conduct limitations of the RCT reported by McVary et al are summarized in Tables 4 and 5. The major limitations were the short follow-up duration in the sham-controlled phase, and lack of blinding, no control group, and high loss to follow-up in the follow-up phase. Additionally, no studies have compared Rezum to medical management, TURP, or other minimally invasive procedures. Because LUTS in men with BPH may improve spontaneously over time, it is important for future studies to include a longer follow-up period with a control group.

Table 4. Study Relevance Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 5. Study Design and Conduct Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Section Summary: Transurethral Water Vapor Thermal Therapy

Rezum effectively reduced symptoms of BPH compared to sham treatment in one RCT with 5 years of follow-up; however, comparisons to TURP or other active therapies are lacking.

For individuals who have BPH and lower urinary tract symptoms (LUTS) who receive transurethral water vapor thermal therapy, the evidence includes one 3-month, sham-controlled, randomized trial of 197 patients with a 5-year uncontrolled follow-up phase. The outcomes of interest are symptoms, functional outcomes, quality of life, and treatment-related morbidity. At 3 months, LUTS improved more in the intervention group compared to the sham procedure. No adverse effects on erectile or ejaculatory function were observed, and improvements were sustained through 5 years of follow-up. The evidence is limited by the small sample size, short-term duration, lack of blinding of longer-term outcomes, and lack of comparison to alternative treatments such as TURP. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Population Reference No. 2

Transurethral Waterjet Ablation (Aquablation)

Clinical Context and Therapy Purpose

The purpose of aquablation in patients who have BPH and LUTS is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is men with BPH and LUTS. Symptoms include urinary frequency, urgency, irregular flow, weak stream, straining, and getting up at night to urinate.

Interventions

The therapy being considered is transurethral waterjet ablation, known as aquablation. Aquablation cuts tissue by using a pressurized jet of fluid delivered to the prostatic urethra. The device is able to image the treatment area, or pairs with an imaging modality, to monitor treatment progress.

Comparators

The following practices and therapies are currently being used to make decisions about aquablation:

• Conservative treatment, including watchful waiting and lifestyle modifications;

• Pharmacotherapy;

• TURP;

• Prostatic urethral lift.

Outcomes

The general outcomes of interest are symptoms, functional outcomes, quality of life, retreatment rates, and treatment-related morbidity.

The International Prostate Symptom Score (IPSS) is used to assess the severity of BPH symptoms. The first 7 questions address urinary frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying, and urgency each on a scale of 0 to 5. The total score, summed across the 7 items measured, ranges from 0 (no symptoms) to 35 (most severe symptoms). A decrease in score indicates improvement.

Quality of life is assessed with various scales including the IPSS-QoL.

Erectile and ejaculatory function is assessed in sexually active men only. Scales include the International Index of Erectile Function and the Male Sexual Health Questionnaire.

Both short-term (up to 12 months) and long-term (12 months and longer) outcomes should be assessed. Treatment-related morbidity can also be assessed in the immediate post-procedure period.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies;

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Review of Evidence

Systematic Review

Elterman et al (2021) performed a meta-analysis of individual patient data from 4 prospective, multicenter trials (N=425) with aquablation in the management of symptomatic BPH (Tables 6 to 8).^10, The 4 studies were WATER (an RCT), WATER II (a prospective single-arm study), OPEN WATER (a prospective single-arm study), and FRANCAIS WATER (an observational study). Each study had at least 1 year of follow-up. Pooled results from all 4 studies showed improvement from baseline in IPSS, IPSS-QoL, maximum urine flow rate, and postvoid residual volume. There were no new cases of erectile dysfunction postoperatively, but 10.8% of men reported new ejaculatory dysfunction.

Table 6. Comparison of Trials/Studies Included in Systematic Review and Meta-Analysis

Table 7. Systematic Review & Meta-Analysis Characteristics

BPH: benign prostatic hyperplasia; RCT: randomized controlled trial.

Table 8. Systematic Review & Meta-Analysis Results

IPSS: International Prostate Symptom Score; PVR: postvoid residual urine volume; Qmax: peak urinary flow rate; QoL: quality of life.

Randomized Controlled Trial

Aquablation for treatment of BPH has been assessed in a single RCT, known as WATER (Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue).^11, WATER was a noninferiority trial comparing aquablation with TURP in 181 participants at 17 sites in 4 countries (Table 9 ). Participants were men ages 45 to 80 years with moderate-to-severe LUTS, defined as an IPSS 10 score ≥12, and prostate size between 30 and 80 mL. The primary efficacy endpoint was the difference between groups in the change in IPSS at 6 months, and the primary safety endpoint was the development of Clavien-Dindo persistent grade 1, or 2 or higher operative complications at 3 months. Primary endpoint results were reported by Gilling et al in 2018,^11, 12-month results in Gilling et al (2019),^15,, 3-year results in Gilling et al (2020) ^16,, and 5-year results in Gilling et al (2022)^17, Additionally, a synthesis of the trial results up to 12 months was reported in a Cochrane systematic review conducted by Hwang et al (2019).^18,

On the primary efficacy outcome in WATER, aquablation was noninferior to TURP. At 6 months, mean IPSS decreased from baseline by 16.9 points for aquablation and 15.1 points for TURP (mean difference, 1.8 points; p<.0001 for noninferiority and p=.1347 for superiority). The primary safety endpoint rate was lower in the aquablation group compared to the TURP group (26% vs. 42% ; p=.0149). The rate of grade 2 and greater events was similar in the 2 groups (20% for aquablation and 23% for TURP; p=.3038).

Table 9. Summary of Key Randomized Controlled Trial Characteristics

IPSS: International Prostate Symptom Score; LUTS: lower urinary tract symptoms; Qmax: peak urinary flow rate; TURP: transurethral resection of the prostate; WATER: Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue.

WATER trial results at 12 months, as summarized in the Cochrane review, are shown in Table 10. The reviewers assessed the certainty of the evidence for each outcome using the GRADE approach.^18, The reviewers concluded that up to 12 months, aquablation likely results in a similar improvement in urologic symptom scores to TURP and may result in similar quality of life when compared to TURP. The authors also concluded that aquablation may result in little to no difference in major adverse events, but considered the evidence for this finding very low certainty due to study limitations and imprecision of estimates.

Table 10. WATER Trial Results at 12 months (Adapted from Hwang et al [2019]^18,)

Source: adapted from Hwang et al (2019)18,

CI: confidence interval; IPSS: International Prostate Symptom Score; QoL: quality of life; RR: relative risk; WATER: Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue.

Gilling et al (2020) and Gilling et al (2022) reported WATER trial results at 3 and 5 years, respectively (Table 11).^16,17, Improvements in symptoms and quality of life were maintained through 3 years in both treatment groups, and the rate of serious adverse events did not differ between groups any any time point. Efficacy was maintained through 5 years as well, but safety results were not reported beyond 3 years.

Table 11. WATER Trial Results at 3 and 5 Years

AE: adverse events; IPSS: International Prostate Symptom Score; NS: not significant; Qmax: peak urinary flow rate; QoL: quality of life; TURP: transurethral resection of the prostate; WATER: Waterjet Ablation Therapy for Endoscopic Resection of Prostate Tissue.

Study design and conduct limitations of the WATER trial are displayed in Tables 12 and 13. Limitations included a lack of blinding of treating clinicians and baseline evaluators, but blinding of study participants makes this less of a concern. Adverse events were adjudicated up to 1 year, but not after 1 year.

Table 12. Study Relevance Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4.Not the intervention of interest.c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 13. Study Design and Conduct Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Section Summary: Transurethral Waterjet Ablation (Aquablation)

Aquablation was compared to TURP in the WATER trial, with follow-up until 5 years. Aquablation was superior to TURP for the primary safety endpoint at 6 months, but few safety results beyond 6 months are available. At 3 years and 5 years, there were no significant differences between groups in IPSS scores.

For individuals who have BPH and LUTS who receive aquablation, the evidence includes a single noninferiority randomized controlled trial (RCT) of aquablation compared to TURP in 187 patients with 5 years of follow-up, and several multicenter, prospective, single-arm studies. The outcomes of interest are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The primary efficacy endpoint in the RCT was the difference between groups in the change in International Prostate Symptom Score (IPSS) at 6 months, and the primary safety endpoint was the development of Clavien-Dindo persistent grade 1, or 2 or higher operative complications at 3 months. At 6 months, mean IPSS decreased from baseline by 16.9 points for aquablation and 15.1 points for TURP (mean difference, 1.8 points; p<.0001 for noninferiority and p=.1347 for superiority). The primary safety endpoint rate was lower in the aquablation group compared to the TURP group (26% vs. 42% ; p=.0149). The rate of grade 2 and greater events was similar in the 2 groups (20% for aquablation and 23% for TURP; p=.3038). Over 5 years, improvements remained similar between groups with no new safety signals. Confidence in these conclusions is reduced due to imprecision of estimates and a lack of additional supportive trials, especially with regard to comparative adverse events. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Supplemental Information

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Urological Association

In 2021, the American Urological Association published guidelines on the surgical evaluation and treatment of lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH). ^19,An amendment to these guidelines was published in 2023.^20, The following recommendations are related to the interventions included in this evidence review:

• Water vapor thermal therapy should be considered as a treatment option for patients with LUTS/BPH provided prostate volume is 30 to 80 g. (Moderate Recommendation; Evidence Level: Grade C)

• Water vapor thermal therapy may be offered as a treatment option to eligible patients who desire preservation of erectile and ejaculatory function. (Conditional Recommendation; Evidence Level: Grade C)

• Robotic waterjet treatment may be offered as a treatment option to patients with LUTS/BPH provided prostate volume is 30 to 80 g. (Conditional Recommendation; Evidence Level: Grade C)

National Institute for Health and Care Excellence

In 2020, the NICE issued the following guidance on Rezum for treatment of LUTS secondary to BPH:^21,

"Evidence supports the case for adopting Rezum for treating lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) in the NHS [National Health Service]. Rezum relieves LUTS and improves quality of life."

"Rezum is a minimally invasive procedure. It should be considered as a treatment option for people with:

• moderate to severe LUTS (International Prostate Symptoms Score [IPSS] typically 13 or over) and

• a moderately enlarged prostate (typically between 30 cm³ and 80 cm³)."

In 2023 , NICE updated guidance on transurethral water jet ablation for LUTS caused by BPH.^22, The following recommendations were made:

"Transurethral water-jet ablation for lower urinary tract symptoms caused by BPH may be used if standard arrangements are in place for clinical governance, consent, and audit. For auditing the outcomes of this procedure, the main efficacy and safety outcomes identified in this guidance can be entered into NICE's interventional procedure outcomes audit tool (for use at local discretion)."

A Medtech innovation briefing was released by NICE in January 2023 but guidance specific to Aquablation is awaiting development.^23,

U.S. Preventive Services Task Force Recommendations

Not applicable.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials

Ongoing trials that might influence this review are listed in Table 14.

Table 14. Summary of Key Trials

aDenotes industry sponsored or cosponsored trialNCT: National Clinical Trial

REFERENCES

1. UpToDate. Medical treatment of benign prostatic hyperplasia. Updated January 2024. Available at: https://www.uptodate.com/contents/medical-treatment-of-benign-prostatic-hyperplasia?search=benign%20prostatic%20hyperplasia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed April 17, 2024.
2. Westwood J, Geraghty R, Jones P, et al. Rezum: a new transurethral water vapour therapy for benign prostatic hyperplasia. Ther Adv Urol. Nov 2018; 10(11): 327-333. PMID 30344644
3. McVary KT, Roehrborn CG. Three-Year Outcomes of the Prospective, Randomized Controlled Rezūm System Study: Convective Radiofrequency Thermal Therapy for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia. Urology. Jan 2018; 111: 1-9. PMID 29122620
4. Food and Drug Administration (2017). Aquabeam System Device Classification Under Section 513(f)(2)(De Novo). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/denovo.cfm?ID=DEN170024. Accessed April 17, 2024.
5. Kang TW, Jung JH, Hwang EC, et al. Convective radiofrequency water vapour thermal therapy for lower urinary tract symptoms in men with benign prostatic hyperplasia. Cochrane Database Syst Rev. Mar 25 2020; 3(3): CD013251. PMID 32212174
6. McVary KT, Gange SN, Gittelman MC, 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. May 2016; 195(5): 1529-1538. PMID 26614889
7. McVary KT, Rogers T, Roehrborn CG. Rezūm Water Vapor Thermal Therapy for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: 4-Year Results From Randomized Controlled Study. Urology. Apr 2019; 126: 171-179. PMID 30677455
8. McVary KT, Gittelman MC, Goldberg KA, et al. Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. J Urol. Sep 2021; 206(3): 715-724. PMID 33872051
9. McVary KT, El-Arabi A, Roehrborn C. Preservation of Sexual Function 5 Years After Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia. Sex Med. Dec 2021; 9(6): 100454. PMID 34731779
10. Elterman D, Gilling P, Roehrborn C, et al. Meta-analysis with individual data of functional outcomes following Aquablation for lower urinary tract symptoms due to BPH in various prostate anatomies. BMJ Surg Interv Health Technol. 2021; 3(1): e000090. PMID 35047807
11. Gilling P, Barber N, Bidair M, et al. WATER: A Double-Blind, Randomized, Controlled Trial of Aquablation ® vs Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia. J Urol. May 2018; 199(5): 1252-1261. PMID 29360529
12. Bhojani N, Bidair M, Kramolowsky E, et al. Aquablation Therapy in Large Prostates (80-150 mL) for Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Final WATER II 5-Year Clinical Trial Results. J Urol. Jul 2023; 210(1): 143-153. PMID 37115632
13. Misrai V, Rijo E, Zorn KC, et al. Waterjet Ablation Therapy for Treating Benign Prostatic Obstruction in Patients with Small- to Medium-size Glands: 12-month Results of the First French Aquablation Clinical Registry. Eur Urol. Nov 2019; 76(5): 667-675. PMID 31281024
14. Bach T, Gilling P, El Hajj A, et al. First Multi-Center All-Comers Study for the Aquablation Procedure. J Clin Med. Feb 24 2020; 9(2). PMID 32102329
15. Gilling PJ, Barber N, Bidair M, et al. Randomized Controlled Trial of Aquablation versus Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia: One-year Outcomes. Urology. Mar 2019; 125: 169-173. PMID 30552937
16. Gilling P, Barber N, Bidair M, et al. Three-year outcomes after Aquablation therapy compared to TURP: results from a blinded randomized trial. Can J Urol. Feb 2020; 27(1): 10072-10079. PMID 32065861
17. Gilling PJ, Barber N, Bidair M, et al. Five-year outcomes for Aquablation therapy compared to TURP: results from a double-blind, randomized trial in men with LUTS due to BPH. Can J Urol. Feb 2022; 29(1): 10960-10968. PMID 35150215
18. Hwang EC, Jung JH, Borofsky M, et al. Aquablation of the prostate for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia. Cochrane Database Syst Rev. Feb 13 2019; 2(2): CD013143. PMID 30759311
19. Lerner LB, McVary KT, Barry MJ, et al. Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART II-Surgical Evaluation and Treatment. J Urol. Oct 2021; 206(4): 818-826. PMID 34384236
20. Sandhu JS, Bixler BR, Dahm P, et al. Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia (BPH): AUA Guideline Amendment 2023. J Urol. Jan 2024; 211(1): 11-19. PMID 37706750
21. National Institute for Health and Care Excellence (2020). Rezum for treating lower urinary tract symptoms secondary to benign prostatic hyperplasia. https://www.nice.org.uk/guidance/mtg49/chapter/1-Recommendations. Accessed April 16, 2024.
22. National Institute for Health and Care Excellence (2023). Transurethral water jet ablation for lower urinary tract symptoms caused by benign prostatic hyperplasia. [IPG770]. https://www.nice.org.uk/guidance/ipg770. Accessed April 17, 2024.
23. National Institute for Health and Care Excellence (NICE). Aquablation robotic therapy for lower urinary tract symptoms caused by benign prostatic hyperplasia. January 1, 2023. https://www.nice.org.uk/advice/mib315/chapter/Clinical-and-technical-evidence. Accessed April 15, 2024.

Codes

Applicable Modifiers

As per correct coding guidelines

Policy History