INTRODUCTION
Benign prostatic hyperplasia (BPH) is a histological diagnosis of proliferation of the smooth muscle and epithelial cells in the transitional zone of the prostate [1]. The prevalence of BPH worldwide ranges from 8% to 80% among men aged 40 to 90, with an age-related increase in incidence [234]. Approximately half of patients with BPH develop significant and bothersome lower urinary tract symptoms (LUTS), including urgency, frequency, incontinence, and nocturia, which can significantly impair quality of life (QoL) [25].
Transurethral resection of the prostate (TURP) is generally considered the standard surgical strategy for BPH [67]. However, TURP can result in adverse events that decrease the patients’ QoL, such as urethral stenosis, irritative incontinence, erectile dysfunction and retrograde ejaculation [89]. Thus, efforts are focusing on developing and implementing new Minimally Invasive Surgical Treatments (MISTs).
Water vapor thermal therapy (WVTT), also known as Rezum, is a MIST that was developed to overcome the limitations of traditional surgical options for treating BPH. WVTT utilizes steam as a heat transport vehicle and has shown positive results in histological research and magnetic resonance imaging [10]. Preservation of adjacent tissue integrity is ensured as there is little thermal effect beyond the treatment area, enabling surgeons to target the obstructing area with precision [11].
A significant benefit of WVTT is that it can preserve sexual function [12]. Compared to TURP, WVTT will not impact erection or ejaculation [13]. McVary et al [14] reported that WVTT had long-term efficacy in improving LUTS over a 5-year follow-up, without adversely affecting ejaculation and erectile function in an elderly population setting.
The recent Food and Drug Administration (FDA) label expansion extends WVTT indications to patients with prostate volumes of 30–150 g, encompassing large glands (>80 g) and median lobe hyperplasia. This broadens applicability to approximately 90% of surgical candidates previously ineligible for MISTs. BPH can be managed with WVTT in an outpatient setting.
Likewise, symptom relief may be achieved over a shorter treatment time (8 minutes on average) [12]. WVTT is considered as an alternative to permanent catheterization for patients with underlying diseases or complications [1516], particularly those unsuitable for TURP.
Several previous studies have been performed to assess the efficacy and safety of the WVTT [171819]. And there were systematic reviews that provided extensive assessments of WVTT. However, no studies to our knowledge have synthesized the multifaceted outcomes of this intervention from these systematic reviews and meta-analyses.
Umbrella review—a recently established methodology in evidence-based medicine—provides a higher level of evidence synthesis by systematically evaluating existing systematic reviews and meta-analyses. It offers a more comprehensive assessment of evidence quality and credibility, along with a clear overview of broad topics. Therefore, we conducted this umbrella review and updated meta-analysis to evaluate contemporary evidence on WVTT for BPH patients, seeking to enhance postoperative outcomes.
It synthesizes the cumulative evidence, identifies consistent findings and disparities, and provides a comprehensive insight into the potential benefits and limitations of WVTT for BPH.
MATERIALS AND METHODS
The review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and in compliance with the reporting guideline of the umbrella review approach [20]. The umbrella review protocol was pre-registered in the Prospective Systematic Reviews Registry under registration identifier CRD42024514038.
1. Search strategy
The literature search was conducted in MEDLINE, Embase, the Cochrane Library, and PubMed from their inception through January 2025. The search targeted systematic reviews and meta-analyses evaluating the clinical applicability, postoperative efficacy, adverse events, retreatment rates, and cost-effectiveness of WVTT. The detailed search strategies are shown in Supplement Material 1.
Moreover, a thorough examination of reference lists in literature reviews and original articles was conducted to ensure that no eligible studies were missed.
2. Selection criteria
Systematic reviews and original studies that satisfied the requirements in Table 1 were included.
The exclusion criteria included (1) article types such as letters, books, and comments; (2) non-English studies; (3) studies whose data could not be extracted; (4) studies lacking accurate follow up duration or using other interventions except WVTT; and (5) duplicate publications. The list of excluded articles can be found in Supplement Material 2.
3. Data extraction and quality assessment
Two reviewers independently extracted the data and summarized the results. Duplicates and irrelevant studies were excluded after screening titles and abstracts. The full text was then thoroughly reviewed to confirm its eligibility, and the following information was extracted for umbrella review: authors, publication year and country where the review was conducted, databases searched, number and type of studies included in each review, and the intervention used to treat BPH.
As to updated meta-analysis, the first author, publication year, follow-up duration, number of patients, International Prostate Symptom Score (IPSS) score, peak urinary flow (Qmax), and postvoid residual volume (PVR) for each review were extracted. IPSS score was the primary outcome. Country, mean prostate volume and study type were included as covariates in meta-regression.
Discrepancies in data extraction between two authors were resolved through discussion with a third author.
The quality of the systematic reviews was evaluated by two authors independently using the AMSTAR 2 tool, which contains 16 questions, and the overall confidence in the results of the review is rated as high, moderate, low, and critically low [21]. Evidence was evaluated using the GRADE system and then graded into “high,” “moderate,” “low,” or “very low” [22]. Two authors independently assessed the quality and risk of bias (RoB) of the studies.
An RoB summary and graphics were generated using RevMan 5.4 (The Cochrane Centre). For prospective and retrospective single-arm studies, RoB was evaluated according to European Association of Urology guidelines for systematic reviews of case series [23].
4. Statistical analysis
Mean differences (MDs) with corresponding 95% confidence intervals (CIs) were employed as summary statistics. Considering the clinical heterogeneity, a random effect was utilized in the meta-analysis. Statistical heterogeneity across trials was assessed by the Cochran Q test (with p<0.1 indicating significance) and quantified by the I2 statistic.
An I2 value greater than 50% was considered significant heterogeneity. Stata 17.0 was used to conduct a random-effects meta-regression to detect the potential source of heterogeneity between studies with covariates including country, mean prostate volume and study type. When data were reported as median and IQR, we used a validated method to calculate mean and SD due to the properties of Review Manager software being able to analyze data only when presented as mean and SD [2425].
RESULTS
1. Description of included studies
For the updated meta-analysis, a total of 241 articles were initially identified. After removing duplicate studies, filtering by title and abstract of the remaining articles and evaluating the full text of possible articles, 25 articles were included in this analysis [8182627282930313233343536373839404142434445464748]. Among the 25 included publications, 21 were retrospective studies, three were prospective, and the remaining one was a randomized controlled trial (RCT).
The article selection process is shown in Fig. 1. The quality assessment of studies included in the update meta-analysis is shown in Supplement Material 3.
For the umbrella review, a total of 57 studies were screened for eligibility. After removal of duplicities and screening of titles and abstracts, 38 records were excluded and 19 additional records were removed after assessment of full texts. Consequently, six systematic reviews met the inclusion criteria for this umbrella review [31649505152], with three containing meta-analyses [505152]
The characteristics of the included systematic reviews are presented in Table 2. An overview of the included meta-analyses is provided in Table 3. Following a comprehensive review of study titles, abstracts, and references, a baseline characteristics table (Table 4) was constructed using the following parameters: authors, year of publication, study design, country, follow-up duration, sample size, type of anesthesia, and primary efficacy endpoint.
Table 5 shows the baseline patient characteristics. The updated meta-analysis evaluated the efficacy of WVTT using IPSS score, Qmax, and PVR as outcome measuring tools. A random-effects model was utilized due to significant heterogeneity among the included studies.
2. IPSS
Out of the 25 eligible studies in the updated meta-analysis, which involved 3,308 patients treated with WVTT up to January 2025, IPSS was estimated in 17 studies at 3 months post-surgery. Our result exhibited a significant decrease (Fig. 2A), with an overall effect size of 10.96 (95% CI, 9.71 to 12.20; p<0.0001) and significant heterogeneity (I2=89%, p<0.00001).
IPSS scores were also decreased at 12 months post-operation (Fig. 2D). The overall effect size was 12.35 (95% CI, 10.74 to 13.95; p<0.00001) with significant heterogeneity (I2=94%, p<0.00001).
In the umbrella review, three studies conducted meta-analyses to access IPSS [505152]. All of them are single-arm meta-analyses, demonstrating significant improvement in IPSS at 3 to 48 months after surgery compared to pre-operation with moderate to significant heterogeneity.
3. Qmax
In the updated meta-analysis, 18 studies were included to investigate the improvement in Qmax at 3 months after surgery (Fig. 2B). These analyses showed a significant effect size of 4.70 (95% CI, 4.22 to 5.19; p<0.00001) improvement with moderate heterogeneity (I2=31%, p=0.08).
14 studies exploring changes in Qmax at 12 months postoperative were included and provided valuable results (Fig. 2E), with an effect size of 5.27 (95% CI, 4.46 to 6.07; p<0.00001) improvement and significant heterogeneity (I2=84%, p<0.00001).
In the umbrella review, improvement of Qmax was estimated in three included meta-analyses [505152], showing significance in 3 to 36 months after surgery compared to baseline data with moderate heterogeneity.
4. PVR
In the updated meta-analysis, PVR after 3 months postoperative was demonstrated according to data from 15 studies (Fig. 2C). It was proved to be decreased with an effect size of 69.52 (95% CI, 52.15 to 86.89; p<0.00001) and significant heterogeneity (I2=84%, p<0.00001).
Additionally, PVR at 12 months postoperative also proved to be decreased (Fig. 2F), with an effect size of 37.07 (95% CI, 18.29 to 55.85; p=0.0001) and significant heterogeneity (I2=97%, p<0.00001).
In our umbrella review, PVR was evaluated in two meta-analyses [5052]. Both showed significant reduction during a median follow-up of 6 months and at 12 months after surgery compared to baseline, respectively.
5. Adverse events
We also collected data on the rate and type of adverse events after WVTT. The incidence of complications (events/total cases×100%) following WVTT is illustrated in the bar graph in Fig. 3, which includes a total of 980 cases based on patients’ preoperative secondary LUTS.
The data came from all 26 studies included in the forest plots. Hematuria was the most commonly reported major adverse event (16.46%), followed by urinary retention (11.12%), dysuria (9.85%) and urinary tract infection (5.88%). Other notable adverse events included prostate tissue sloughing (2.49%), erectile dysfunction (2.06%), and hemospermia (1.41%).
Retrograde ejaculation was observed in 0.40% of patients.
According to the six articles included in the umbrella review, although WVTT had a modest incidence of adverse events, its effects were often transient. Most of the reported adverse events were minor within three months since surgery and disappeared within three weeks. No studies have reported an association between WVTT and any serious complications (classified as grade 3 or higher according to Clavien-Dindo).
6. Publication bias and meta-regression
primary outcome was evaluated by funnel plots (Supplement Material 4). The figure was in the shape of an inverted funnel, which was basically symmetrical, suggesting that the publication bias was small. A sensitivity analysis was performed to assess the influence of individual studies.
After excluding any study that did not influence the direction and magnitude of the cumulative estimates substantially, we obtained similar results.
To investigate potential sources of high heterogeneity, a random-effects meta-regression was performed for each outcome measure with country, study design, and mean prostate volume prespecified as covariates. Statistical significance was defined as p<0.05, indicating a significant contributor to heterogeneity. Meta-regression identified study design as a significant source of heterogeneity for 3-month postoperative IPSS (p=0.023), and country for 12-month postoperative Qmax (p=0.004) and PVR (p=0.012).
Complete meta-regression results are presented in Supplement Material 5.
7. AMSTAR and GRADE classification
The AMSTAR ratings of most systematic reviews were low, with some being critically low. As the majority of included systematic reviews incorporated singlearm observational studies, the overall quality of evidence according to GRADE ratings was predominantly low. Only the meta-analysis conducted by Miller et al [51] was rated as moderate.
Detailed results for all studies are presented in Table 2.
DISCUSSION
LUTS secondary to BPH significantly compromises elderly men’s QoL. Urinary retention and other severe symptoms constitute absolute indications for surgery. While TURP remains the gold standard, WVTT, a type of MIST, is increasingly utilized.
Prior work has addressed the efficacy and safety of WVTT in improving IPSS, Qmax and PVR. Systematic reviews have also been conducted by many scholars. However, these studies either lacked comprehensiveness or did not utilize visualized quantitative methods to present data.
In order to better understand the overall advantages and disadvantages of WVTT for men with BPH, we performed an updated single-arm meta-analysis and umbrella review.
The efficacy of WVTT in improving LUTS secondary to BPH is well documented, although comparative long-term data remain limited and inconclusive. A prospective study conducted by Dixon et al [1047] was the first to evaluate the long-term efficacy of WVTT reporting IPSS score reductions of up to 56% and 55% at 12 and 24 months, respectively (p<0.001). Similarly, McVary and Roehrborn [42] observed substantial IPSS improvements within 3–12 months postoperatively.
Our updated meta-analysis further supports these findings, showing an average IPSS reduction of 10.96 points at 3 months and 12.35 points at 12 months post-treatment. All the included systematic reviews in our umbrella review confirmed sustained IPSS improvement following WVTT.
In addition to voiding symptom relief, WVTT has demonstrated objective improvements in urinary flow and bladder emptying. In the prospective nonrandomized trial conducted by Dixon et al [1047], significant improvements in Qmax and PVR were observed within the first month after the procedure. These improvements reached their maximum at 3 months and continued through 24 months of follow-up.
Our present data analysis revealed a decrease in PVR by 69.52 mL at 3 months and 37.07 mL at 12 months after WVTT, alongside Qmax increases of 4.70 and 5.27 mL/s at corresponding time points.
Comparative data between WVTT and other surgical options are less definitive. A Cochrane network meta-analysis by Franco et al [13] indicated that WVTT may be associated with worse IPSS compared to TURP at short-term follow-up (MD 3.6 points), but the result did not reach statistical significance. Another study stated that there were no consistently significant differences in IPSS when comparing WVTT with Aquablation or prostatic artery embolization (PAE) at 3 months after surgery [53].
Regarding Qmax and PVR, Indirect comparisons of TURP and WVTT revealed no significant differences at the 3-month follow up [53]. This may indicate that the short-term efficacy of WVTT in improving urinary flow and bladder emptying may be comparable to that of TURP. As to other MIST, a significant difference in Qmax was shown in favor of Aquablation compared to WVTT [54].
Indirect comparison indicates WVTT achieves greater Qmax improvement at 1 year (5.27 mL/s) than prostatic urethral lift (3.8 mL/s), despite absence of head-to-head studies [55]. Nevertheless, due to the indirect nature of these comparisons, further high-quality studies with extended follow-up are warranted to confirm the superiority of WVTT compared to other therapeutic approaches.
Despite the aforementioned efficacy of WVTT, there are general concerns about its applicability in patients with large prostates, middle lobe obstruction, and indwelling catheters. The improvement in IPSS, PVR and other indicators after WVTT in patients with different gland sizes was analyzed in two studies which compared the effects of WVTT in large and small prostates [2756]. Bole et al [27] demonstrated safety and effectiveness 3 months after WVTT, with statistically significant improvements in patients with large glands.
Garden et al [56] found that WVTT could remain effective in improving Qmax and reducing PVR in patients with large prostates 1 year after surgery. The curative effect can still be maintained 1 year after the procedure. The 2025 FDA label expansion for WVTT extends its indication to prostate volumes ≤150 g, significantly broadening its clinical utility in minimally invasive BPH management.
This major milestone formally establishes WVTT as a validated therapeutic option for individuals with large-volume prostates (80–150 g), substantially expanding the eligible patient population previously limited to glands ≤80 g. Perioperative continuation of antiplatelet/anticoagulation therapy during WVTT in a Singaporean cohort appears to be safe, with no increase in major complications despite a slight trend toward higher overall complication rates [48]. Furthermore, consensus supports WVTT’s therapeutic utility for moderate-to-severe symptomatic patients, demonstrating applicability encompassing those above and below 65 years [57].
These findings expand the applicable population of WVTT, especially for patients unable or unwilling to undergo TURP under general anesthesia.
Current evidence suggests that WVTT has a minimal impact on sexual function. According to our umbrella review, WVTT has no significant effect on sexual function, which is consistent with the previous studies by Dixon et al [47] and McVary and Roehrborn [42]. They found no clinically significant changes in sexual function over the 2-year assessments and no negative changes in International Index of Erectile Function erectile function domain and Male Sexual Health Questionnaire for Ejaculatory Dysfunction function scores throughout 3 years of follow-up respectively.
Given incomplete outcome data in the newly published study, meta-analysis was not updated for sexual function outcomes. In a network meta-analysis, Franco et al [13] concluded that WVTT and temporary implantable nitinol device (TIND) had the highest probability of preserving erectile function, whereas TURP ranked lowest among the compared interventions. WVTT may also result in no significance in events of ejaculatory dysfunction compared to sham treatment at short-term follow-up (relative risk, 4.01; 95% CI, 0.22 to 72.78; p>0.05).
Thus, WVTT is less likely to affect sexual function, making it a suitable choice for sexually active BPH patients and meeting patients’ pursuit of life quality.
Our umbrella review showed that WVTT has a low retreatment rate that varies from 1.2% to 4.4%, sharing similarity with prior studies. In the RCT conducted by McVary and Roehrborn [42], the surgical retreatment rate after WVTT was 4.4% (6 of 135 subjects) over 3 years of follow-up. In a cohort of 83 men with prostates ≥80 mL, two (2.4%) underwent photoselective vaporization of the prostate (PVP) within 12 months after WVTT [38].
A network meta-analysis indicated that WVTT has a lower retreatment rate than TURP, PAE and TIND at 6 months. By 12 months, however, TURP exhibited the lowest retreatment risk and ranked highest among all interventions [58]. WVTT achieves a notably low retreatment rate within the first postoperative year.
However, the absence of robust long-term data tempers the certainty of this evidence.
WVTT demonstrates a favorable safety profile, predominantly marked by transient and mild adverse events. Our pooled analysis revealed several postoperative complications, among which hematuria (16.46%) and urinary retention (11.12%) were the most frequently reported. Critically, all six studies included in this umbrella review consistently described these adverse events as typically mild and self-limiting.
This aligns with evidence from a network meta-analysis indicating that WVTT achieves a significant reduction in major adverse events compared to TURP [52]. The transient nature of WVTT-related complications is further corroborated by long-term safety data. Analysis of a large-scale database identified a substantially higher incidence of urethral stricture following TURP (4.48%) [59].
In contrast, multivariable analysis confirmed that MIST, including WVTT (1.05%), Aquablation (1.59%), and PAE (0.65%), were associated with a significantly reduced risk of urethral stricture relative to TURP [59]. Collectively, the low incidence and transient character of WVTT-associated adverse events, coupled with its reduced risk of serious complications like urethral stricture, underscore its enhanced safety. These findings may broaden the applicability of WVTT, particularly for patients unsuitable for or intolerant of conventional surgical interventions such as TURP.
The economic implications of BPH management should also be factored into clinical decision-making. Our umbrella review suggests WVTT demonstrates high cost-effectiveness, consistent with prior analyses [60]. However, WVTT’s cost-effectiveness varies across regions, influenced by economic development and healthcare policies.
Most evidence, predominantly derived from US Medicare data using Markov models, supports this finding. For instance, Chughtai et al [61] projected 5-year total Medicare costs at $6,328 for TURP vs. $2,655 for WVTT, modeling costs based on efficacy, adverse events, retreatment rates, and follow-up care. Similarly, a Singapore-based Markov model indicated WVTT provides better value than medication as initial treatment for patients with moderate-to-severe BPH (IPSS 8–35) [62].
TURP is most cost-effective as first-line only for severe BPH cases (IPSS 20–35) [62].
This umbrella review and updated meta-analysis synthesizes recent evidence from a systematic and comprehensive search, incorporating a larger number of relevant studies than previous meta-analyses. However, this work has several limitations. Firstly, the included studies were predominantly single-arm, observational, and retrospective, introducing potential confounders and bias.
Secondly, adverse event incidence, particularly sexual adverse events, may be underestimated due to follow-up losses and assessment methods. Thirdly, only three studies reported follow-up exceeding 12 months, highlighting the need for longer-term outcomes and direct comparisons with other treatments. The current evidence level is limited, necessitating more RCTs and prospective studies.
Furthermore, the umbrella review methodology inherently restricted the number of included systematic reviews. Unpublished data were not considered, introducing potential selection bias. Significant heterogeneity was observed, attributable to variations in study design, region, interventions, and patient characteristics; despite meta-regression, residual heterogeneity remains unexplained.
CONCLUSIONS
Significant evidence supports the use of WVTT for lowering IPSS and PVR, increasing Qmax and alleviating LUTS symptoms associated with BPH. As an emerging MIST, WVTT has the characteristics of good efficacy, wide application scenarios, low retreatment rate, high safety and high cost-effectiveness. In the current trend of avoiding more invasive surgery, pursuing sexual function preservation and reducing cost, WVTT is a safe, effective and attractive treatment method.
In the future, higher level prospective cohort studies, larger study groups, longer follow-up periods and comparisons of multiple surgical methods are needed to clarify the therapeutic efficacy of WVTT.