Transurethral Water Vapor Thermal Therapy for Benign Prostatic Hyperplasia
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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 through the 510(k) process ( K150786). The Food and Drug Administration 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 <80cm,3 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 Rezum® Procedure (A55352) noting that the Rezum® procedure for treatment of BPH is currently under review, and instructing that CPT code 53854 should be used for billing the procedure.
[RATIONALE: 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 (QOL), 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, andquality 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 PICOs were used to select literature to inform this review.
The relevant population of interest are men withBPH.
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.
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, QOL, 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 7items measured, ranges from 0 (no symptoms) to 35 (most severe symptoms). A decrease in score indicates improvement.
QOL 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. In an RCT, 69% of patients received oral sedation only, 21% received a prostate block, and 10% received intravenous sedation.
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.
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).4,
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).5, 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.
|McVary et al. (2015,4, 20183,), 20195,
|US||15||2013-2016||Men with moderate to severe symptomatic BPH, at least 50 years of age (61% were under age 65) with IPSS ≥13, a prostate volume of 30 cc to 80 cc, maximum urinary|
flow rate (Qmax) of ≤15 mL/s, and a measured postvoid residual (PVR) urine <250 mL.
Exclusion criteria included a prostate
specific antigen >2.5 ng/mL with a free prostate specific antigen <25% (unless prostate cancer was ruled out by biopsy) and an active urinary tract infection.
Transurethral water vapor thermal therapy (Rezum)
Sham procedure with rigid cystoscopy and activation of the system generator
outside the subject's body to mimic the sound of the active procedure.
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 QOL.
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
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; RCT: randomized controlled trial.
|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)4,|
|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%)|
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 QOL 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 (2019)5,
SD: standard deviation; N: number analyzed; IPSS: International Prostate Symptom Score; Qmax: peak urinary flow; PVR: postvoid residual urine volume; BPHII: BPH Impact Index IIEF-EF: International Index of Erectile Function; MSHQ-EjD: Male Sexual Health Questionnaire for Ejaculatory Dysfunction.
Notable relevance and study design and conduct limitations of the RCT reported by McVary et al (2015,4, 2018,3, 20195,) 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. 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)4,||2
Sham procedure; no comparison to alternative treatments
Clinically significant difference on symptoms not prespecified
|McVary et al (2018)3, and McVary et al (2019)5,||2
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.
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 BPH who receive transurethral water vapor thermal therapy, the evidence includes one small, short-term sham-controlled RCT with a four-year uncontrolled follow-up phase. The outcomes of interest are symptoms, QOL, 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. This 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 the effects of the technology on health outcomes.
Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.
Practice Guidelines and Position Statements
The American Urological Association (2018) issued clinical practice guidelines on benign prostatic hyperplasia (amended 2019) and made the following recommendations for water vapor thermal therapy6,:
The recommendations were based on results of the randomized controlled trial conducted by McVary et al. (2015,4, 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 review are listed in Table 6.
Table 6. Summary of Key Trials
NCT: National Clinical Trial]
|NCT No.||Trial Name||Planned Enrollment||Completion Date|
|NCT03605745||Minimally InvasiveProstatic Vapor Ablation- Multicenter, Single-Arm Study for the Treatment of BPH in LargeProstates(RezÅ«m XL)||88||Aug 2019|
|NCT02940392||RezumFirst in Man Feasibility Study for the Treatment of BPH With theRezumSystem||15||Jun 2018 (status unknown)|
|NCT02943070||NxThera Benign Prostatic HyperplasiaRezumSystem Pilot Study||50||Dec 2018 (status unknown)|
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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 28, 2019.
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 RezÅ«m 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. 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
5. McVary, KK, Rogers, TT, Roehrborn, CC. RezÅ«m 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
6. 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 28, 2019.
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