Transurethral Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
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- With benign prostatic hyperplasia and lower urinary tract symptoms
Interventions of interest are:
- Transurethral water vapor thermal therapy
Comparators of interest are:
- Conservative approaches
- Medical therapy
- Transurethral resection of the prostate
- Other minimally invasive procedures
Relevant outcomes include:
- Functional outcomes
- Quality of life
- Procedure-related morbidity
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 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.
Transurethral water vapor thermal therapy has been investigated as a minimally invasive alternative to transurethral resection of the prostate. The procedure uses radiofrequency-generated water vapor (~103°C) thermal energy to ablate prostate tissue.3,
In September 2016, the Rezum System™ (NxThera, Inc) 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.
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
Transurethral water vapor thermal therapy is considered investigational as a treatment of benign prostatic hyperplasia.
Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
There is no National Coverage Determination (NCD) for Transurethral Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia. In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a coverage determination for this service. However, Novitas has issued Local Coverage Article: Billing and Coding for RezumŪ Procedure (A55352) noting that the RezumŪ procedure for treatment of BPH is currently under review, and instructing that CPT code 53854 should be used for billing the procedure.
This policy was created in 2019 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through May 14, 2020.
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, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one 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. RCTs 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.
Clinical Context and Therapy Purpose
The purpose of transurethral water vapor thermal therapy in patients who have benign prostatic hyperplasia (BPH) is to provide a treatment option that is an alternative to or an improvement on existing therapies such as transurethral resection of the prostate (TURP).
The question addressed in this policy is: Does transurethral water vapor thermal therapy improve the net health outcome in patients with BPH?
The following PICO was used to select literature to inform this policy.
The relevant population of interest is men with BPH.
Symptoms include urinary frequency, urgency, irregular flow, weak stream, straining and getting up at night to urinate.
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.
The procedure is typically performed in an outpatient setting. 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.
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
- Other minimally invasive procedures
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:
a. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
b. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
c. 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
Kang et al (2020) conducted a Cochrane review of transurethral water vapor thermal therapy for management of LUTS in men with BPH.4, In literature searches conducted through February 2020, the reviewers identified only one RCT (McVary et al ,5, 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 one RCT conducted in 197 men (Table 1). Three-month results were reported in McVary et al (2015).5,
The trial also had an uncontrolled, open-label crossover phase. After unblinding at three 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).6, These results are shown in Table 1.
Table 1. Summary of Key RCT Characteristics
BPH: benign prostatic hyperplasia; IPSS: International Prostate Symptom Score: RCT: randomized controlled trial.
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 three months post-treatment. The secondary outcome was the percentage of responders at three 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, vs 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 three months. There were significant differences in other measures of lower urinary tract symptoms 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.
Two patients in the Rezum group experienced three serious procedure-related adverse events: one patient had de novo extended urinary retention and another had nausea and vomiting due to alprazolam and was hospitalized overnight for observation.
Table 2. Summary of Key RCT Results
|Study||IPSS change from baseline||Responders (30% improvement in IPSS)||IPSS QoL||Qmax (mL/s)||BPHII||IIEF-EF||MSHQ-EjD function||MSHQ-EjD bother||Serious AEs|
|McVary et al, (2015)5,|
|Rezum||-11.2 (7.6)||106/136 (77.9%)||-2.1 (1.6)||6.2 (7.1)||-3.4 (3.5)||0.1 (7.4)||0.3 (4.3)||-0.4 (1.9)||66/136 (48.5%)|
|Sham||-4.3 (6.9)||21/61 (59.5%)||-0.9 (1.5)||0.5 (4.2)||-1.5 (3.0)||-1.5 (3.0)||-0.2 (3.2)||-0.2 (1.9)||4/61 (6.6%)|
AE: adverse events; BPH: benign prostatic hyperplasia Impact Index; IPSS: International Prostate Symptom Score; MSHQ-ED Male Sexual Health Questionnaire-Erectile Dysfunction; IIEF: International Index of Erectile Function; NR: not reported; Qmax: peak urinary flow; QoL: quality of life; RCT: randomized controlled trial.
The trial also had an uncontrolled, open-label crossover phase, reported in McVary et al (2018) and McVary et al (2019). After unblinding at three months, control subjects who elected to proceed were requalified for the crossover study. A total of 97 patients were followed through 36 months. These results are shown in Table 3. Urinary symptoms and quality of life remained significantly improved from baseline up to four years.
The surgical retreatment rate was 4.4 percent over four years.
Table 3. Results of open-label uncontrolled crossover phase (McVary et al 3, and McVary et al 6,)
|Outcome, mean change from baseline (SD)||3 months||6 months||12 months||24 months||36 months||48 months|
|Change||-11.3 (7.6)||-12.2 (7.6)||-11.6 (7.3)||-11.2 (7.3)||-11.0 (7.1)||-10.1 (7.6)|
|Change||6.4 (7.2)||5,7 (6.2)||5.5 (6.4)||4.8 (6.1)||3.5 (4.7)||4.2 (5.7)|
|Change||-10.6 (68.3)||-8.4 (75.8)||-3.9 (82.7)||-0.3 (85.3)||-26.4 (63.9)||-9.2 (72.2)|
|Change||-3.4 (3.5)||-4.1 (3.0)||-3.9 (3.3)||-3.8 (3.1)||-3.7 (3.3)||-3.5 (3.4)|
|Change||0.1 (7.4)||-0.3 (6.4)||-0.3 (7.5)||-1.2 (7.6)||-1.9 (8.2)||-2.5 (8.7)|
|change||0.3 (4.3)||0.1 (3.6)||-0.3 (3.5)||-0.5 (4.2)||-1.4 (3.8)||-1.8 (4.4)|
|change||-0.3 (1.9)||-0.4 (1.9)||-0.7 (1.8)||-0.5 (1.7)||-0.5 (1.6)||-0.1 (1.8)|
BPHII: BPH Impact Index; IPSS: International Prostate Symptom Score; IIEF-EF: International Index of Erectile Function; MSHQ-EjD: Male Sexual Health Questionnaire for Ejaculatory Dysfunction; N: number analyzed; PVR: postvoid residual urine volume; Qmax: peak urinary flow; QoL: quality of life; SD: standard deviation.
Notable relevance and study design and conduct limitations of the RCT reported by McVary et al (2015,5, 2018,3, 20196,) 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 lower urinary tract symptoms 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 limitations assessment.
|McVary et al (2015)5,||Sham procedure; no comparison to alternative treatments||Clinically significant difference on symptoms not prespecified||1, 23 months|
|McVary et al (2018)3, and McVary et al (2019)6,||No control group (comparison to baseline only)||Clinically significant difference in symptom outcomes not prespecified|
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 limitations assessment.
|Study||Allocationa||Blindingb||Selective Reportingc||Data Completenessd||Powere||Statisticalf|
|McVary et al (2015)5,||3 Small sample size|
|McVary et al (2018)3, and McVary et al (2019)6,||1, 2, 3 open label||High loss to follow-up (97/197 [49%] had 3-year data on primary outcome, 90/197 (46%) had 4-year data)||3 Small sample size|
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.
Summary of Evidence
For individuals who have benign prostatic hyperplasia who receive transurethral water vapor thermal therapy, the evidence includes one small, short-term sham-controlled randomized controlled trial with a four-year uncontrolled follow-up phase. The outcomes of interest are symptoms, quality of life, and treatment-related morbidity. At three months, lower urinary tract symptoms 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 four 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 transurethral resection of the prostate. The evidence is insufficient to determine the effects of the technology on health outcomes.
Practice Guidelines and Position Statements
American Urological Association
The American Urological Association (2018) issued clinical practice guidelines on benign prostatic hyperplasia (amended 2019) and made the following recommendations for water vapor thermal therapy7,:
The recommendations were based on results of the randomized controlled trial conducted by McVary et al. (2015,5, 20183,), and this body of evidence was considered low strength, leading to a conditional recommendation (Grade C).
- Water vapor thermal therapy may be offered to patients with lower urinary tract symptoms attributed to benign prostatic hyperplasia provided prostate volume <80 g; however, patients should be counseled regarding efficacy and retreatment rates. (Conditional Recommendation; Evidence Level: Grade C)
- Water vapor thermal therapy may be offered to eligible patients who desire preservation of erectile and ejaculatory function. (Conditional Recommendation; Evidence Level: Grade C)
U.S. Preventive Services Task Force Recommendations
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this policy are listed in Table 6.
Table 6. Summary of Key Trials
|NCT No.||Trial Name||Planned Enrollment||Completion Date|
|NCT03605745a||Minimally Invasive Prostatic Vapor Ablation- Multicenter, Single-Arm Study for the Treatment of BPH in Large Prostates(Rezūm XL)||88||Mar 2023|
|NCT04338776a||C.L.E.A.R. - Comparing UroLift Experience Against Rezum||120||Jan 2022|
|NCT02940392a||Rezum First in Man Feasibility Study for the Treatment of BPH With the Rezum System||15||Jun 2018 (completed)|
|NCT02943070a||NxThera Benign Prostatic Hyperplasia Rezum System Pilot Study||50||Dec 2018 (completed)|
aDenotes industry sponsored or cosponsored trial
NCT: National Clinical Trial]
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
Transurethral Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia
Benign Prostatic Hyperplasia, Transurethral Water Vapor Thermal Therapy for
Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia
Water Vapor Energy Ablation (WAVE) for Benign Prostatic Hyperplasia
WAVE (Water Vapor Energy Ablation) for Benign Prostatic Hyperplasia
1. UpToDate. Medical treatment of benign prostatic hyperplasia. 2019. 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 May 18, 2020.
2. Westwood, JJ, Geraghty, RR, Jones, PP, Rai, BB, Somani, BB. Rezum: a new transurethral water vapour therapy for benign prostatic hyperplasia.. Ther Adv Urol, 2018 Oct 23;10(11). PMID 30344644
3. McVary, KK, Roehrborn, CC. Three-Year Outcomes of the Prospective, Randomized Controlled Rezm System Study: Convective Radiofrequency Thermal Therapy for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.. Urology, 2017 Nov 11;111:1-9. PMID 29122620
4. 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: CD013251. PMID 32212174
5. McVary, KK, Gange, SS, Gittelman, MM, Goldberg, KK, Patel, KK, Shore, NN, Levin, RR, Rousseau, MM, Beahrs, JJ, Kaminetsky, JJ, Cowan, BB, Cantrill, CC, Mynderse, LL, Ulchaker, JJ, Larson, TT, Dixon, CC, Roehrborn, CC. 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., 2015 Nov 29;195(5). PMID 26614889
6. McVary, KK, Rogers, TT, Roehrborn, CC. Rezm Water Vapor Thermal Therapy for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: 4-Year Results From Randomized Controlled Study.. Urology, 2019 Jan 25;126:171-179. PMID 30677455
7. American Urological Association Benign Prostatic Hyperplasia: Surgical Management of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms, 2018 (amended 2019) Available at: https://www.auanet.org/guidelines/benign-prostatic-hyperplasia-(bph)-guideline. Accessed May 18, 2020.
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