Association between volume per injection and treatment failure after water vapor thermal therapy

Abstract

Background

Water vapor thermal therapy (WVTT) determines the injection strategy primarily according to prostatic urethral length. However, no quantitative indicator integrates prostate size and injection number. This study evaluated the association between volume per injection (VPI), defined as prostate volume divided by the number of injections, and treatment failure after WVTT.

Methods

This retrospective study included 105 consecutive patients who received WVTT. Treatment failure represented the first occurrence of medication resumption, re-catheterization, or re-surgery. The Cox proportional hazards models were used to assess the association between continuous VPI and treatment failure. A multivariable model including the use of 5-alpha reductase inhibitor (5-ARI) was utilized in the sensitivity analysis.

Results

During a median follow-up of 455 (95% confidence interval [CI]: 377–538) days, 15 patients experienced treatment failure. A higher VPI was associated with an increased risk of treatment failure in the univariate analysis (hazard ratio per 1-mL increase: 1.21, 95% CI: 1.03–1.42, p = 0.020). The association remained significant after adjusting for the use of 5-ARI (hazard ratio: 1.23, 95% CI: 1.04–1.45, p = 0.018).

Conclusions

A higher VPI was associated with an increased risk of treatment failure after WVTT for BPH. These findings suggest a potential relationship between injection density relative to prostate size and treatment durability. However, given the exploratory nature of the study and the limited number of events, the results should be interpreted with caution. Further prospective validation is warranted.

Introduction

Benign prostatic hyperplasia (BPH), a common condition among aging men, is one of the major causes of lower urinary tract symptoms (LUTS) [1]. Pharmacological therapy remains the first-line treatment for BPH [2]. However, drug resistance, adverse effects, and the burden of long-term medication have increased the demand for minimally invasive therapeutic options, including water vapor thermal therapy (WVTT) [3–5]. In previous single-center studies, WVTT had favorable clinical outcomes from 3 months to 1 year after the procedure [6, 7]. However, factors associated with long-term treatment durability remain incompletely understood.

According to the original technical framework of WVTT, the number of injections is generally determined based on the manufacturer’s recommendations, with injection planning primarily guided by the length of the prostatic urethra and injections placed approximately 1 cm apart along each prostatic lobe [8–10]. Additional injections to the median lobe may be performed if clinically indicated [11].

Recent studies have shown that technical parameters, including the number of injections [12, 13], prostate volume (PV) [14], and injection density [15], may influence treatment outcomes. However, standardized quantitative indicators integrating prostate size and injection number have not been established, and their clinical relevance remains unclear.

The current study introduced volume per injection (VPI), calculated as prostate volume divided by the number of injections, and evaluated its association with treatment failure after WVTT to assess its potential clinical relevance in injection planning.

Methods

Study design and patient population

This single-center retrospective cohort study included consecutive patients who received WVTT for benign prostatic hyperplasia (BPH) between May 2023 and January 2025. The Ethics Committee of Medical Corporation Koshin-Kai approved the study (approval number: KS1003). All patients treated during the study period were eligible for inclusion.

The predefined exclusion criteria included the following: (1) patients with suspected or confirmed prostate cancer, (2) those with a previous history of prostate surgery or minimally invasive BPH treatment, (3) those with neurogenic bladder or other neurological disorders affecting voiding function, and (4) those with active urinary tract infection. None of the patients met the exclusion criteria, and all consecutive patients were included to decrease selection bias.

WVTT procedure and injection strategy

WVTT was performed using the Rezūm™ system (Boston Scientific, Marlborough, MA, the United States), according to the manufacturer’s instructions. The number of injections was determined primarily based on prostatic urethral length, with injections placed at approximately 1-cm intervals along each prostatic lobe. Additional injections were delivered to the median lobe if clinically indicated. All procedures were performed by a single experienced urologist as outpatient day-case surgery under spinal anesthesia.

Definition of VPI

VPI was calculated by dividing PV by the total number of injections delivered during WVTT. Preoperative PV was measured using transabdominal ultrasonography. VPI was analyzed as a continuous variable.

Data collection and assessment of outcome measures

The baseline clinical variables included age, PV, postvoid residual volume (PVR), prostate-specific antigen (PSA) levels, International Prostate Symptom Score quality of life (IPSS-QOL), number of injections, preoperative catheterization status, and use of 5-alpha reductase inhibitors (5-ARI).

Outcomes

The primary endpoint was time to treatment failure after WVTT. Treatment failure was defined as medication resumption for BPH, re-catheterization, or re-surgery. Time to event was calculated from the date of WVTT to the first occurrence of treatment failure. If multiple failure events occurred on the same day, events were classified according to a predefined hierarchical order (reoperation > re-catheterization > medication resumption). Patients without treatment failure were censored at the last confirmed follow-up date.

Statistical analysis

Continuous variables were summarized as median (interquartile range), and categorical variables were expressed as number (percentage). Normality was assessed using the Shapiro–Wilk test. The association between continuous VPI and time to treatment failure was evaluated using the Cox proportional hazards regression model. Univariate analysis was conducted to assess VPI alone, and a multivariable model adjusted for the use of 5-ARI was constructed for sensitivity analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. All statistical analyses were performed using the JASP software (version 0.18.3; JASP Team; https://jasp-stats.org/). A two-sided p value of < 0.05 indicated statistically significant differences. The median follow-up duration was estimated using the reverse Kaplan–Meier method.

Results

Study population

Between May 2023 and January 2025, 105 consecutive patients who received WVTT were included in the survival analysis (Fig. 1). During a median follow-up of 455 (95% CI: 377–538) days, 15 (14.3%) patients experienced treatment failure. Treatment failure comprised medication resumption in 11 (10.5%) patients, re-catheterization in 3 (2.9%), and re-surgery in 1 (1.0%) (Table 1). The single re-surgery consisted of repeat WVTT. The remaining 90 patients were censored without treatment failure.

Fig. 1.

Flow diagram of patient inclusion and treatment failure analysis after WVTT. Treatment failure was defined as the first occurrence of medication resumption, re-catheterization, or re-surgery

Table 1.

Details of treatment failure events (n = 15)

Failure type	n	% of total (n = 105)	% of failures (n = 15)
Medication resumption	11	10.5%	73.3%
Re-catheterization	3	2.9%	20.0%
Re-surgery	1	1.0%	6.7%

Treatment failure was defined as the first occurrence of medication resumption, re-catheterization, or re-surgery

In cases of simultaneous events, the classification followed a predefined hierarchical order (re-surgery > re-catheterization > medication resumption)

Baseline characteristics of the patients

Table 2 shows the baseline characteristics of the patients. The median age was 72 (interquartile range [IQR]: 66–76) years, and the median PV was 49.5 (IQR: 37.4–61.4) mL. The median VPI was 9.11 (IQR: 7.88–11.22) mL. In total, 19 (18.1%) patients had preoperative catheterization, and 65 (61.9%) patients were receiving 5-ARI therapy at baseline.

Table 2.

Baseline characteristics of the study population

Variables	All patients (N = 105)
Age, years	72 (66–76)
PV, mL	49.5 (37.4–61.4)
PVR, mL	41.0 (11.5–75.3)
IPSS-QOL	5 (4–5)
PSA level, ng/mL	3.91 (2.35–7.07)
Number of injections	5 (4–6)
VPI, mL	9.11 (7.88–11.22)
Preoperative catheterization, n (%)	19 (18.1%)
Use of 5-ARI, n (%)	65 (61.9%)

Continuous variables were presented as median (interquartile range), and categorical variables were expressed as number (percentage)

PV prostate volume, PVR postvoid residual volume, IPSS-QOL International Prostate Symptom Score quality of life, PSA prostate-specific antigen, VPI volume per injection, 5-ARI 5-alpha reductase inhibitor

Association between VPI and treatment failure

In the univariate Cox proportional hazards analysis, a higher VPI was significantly associated with an increased risk of treatment failure (HR per 1-mL increase: 1.21, 95% CI: 1.03–1.42, p = 0.020) (Table 3). In the multivariable model adjusted for the use of 5-ARI, VPI remained associated with treatment failure (HR: 1.23, 95% CI: 1.04–1.45, p = 0.018). The proportional hazards assumption was assessed using Schoenfeld residuals and was not violated.

Table 3.

Association between VPI and treatment failure

Variables	Model 1 HR (95% CI)	p value	Model 2 HR (95% CI)	p value
VPI (per 1-mL increase)	1.21 (1.03–1.42)	0.020	1.23 (1.04–1.45)	0.018
Use of 5-ARI	—	—	0.70 (0.24–2.09)	0.526

Model 1: Univariate Cox proportional hazards analysis

Model 2: Multivariable Cox model adjusted for the use of 5-ARI

Treatment failure was defined as the first occurrence of medication resumption, re-catheterization, or re-surgery. The proportional hazards assumption was satisfied

HR hazard ratio, CI confidence interval, VPI volume per injection, 5-ARI 5-alpha reductase inhibitor

Discussion

The current study evaluated the association between VPI and treatment failure after WVTT for BPH. A higher VPI was associated with an increased risk of treatment failure after adjustment for the use of 5-ARI. These findings suggest a potential relationship between injection density relative to prostate size and procedural durability. However, given the exploratory nature of this study, the observed association should be interpreted with caution.

Treatment failure was defined as the first occurrence of medication resumption, re-catheterization, or re-surgery. This composite endpoint reflects clinically significant retreatment events rather than short-term functional changes alone. Medication resumption accounted for most events. However, re-catheterization and re-surgery represent more invasive consequences of insufficient or recurrent obstruction. Therefore, they contribute to the overall assessment of durability. In the present study, treatment failure was primarily driven by medication resumption, which represents a relatively soft endpoint. However, medication resumption reflects the need for additional therapy in real-world clinical practice and may serve as a pragmatic indicator of treatment durability following WVTT. Nevertheless, this definition may be influenced by physician and patient preferences and thus should be interpreted with caution.

Injection planning in WVTT is typically guided by prostatic urethral length [8–10]. However, PV is not necessarily correlated with urethral length [16], and some patients present with substantial variability in gland size and tissue distribution [16, 17]. Consequently, injection number determined primarily by urethral length may not proportionally reflect prostate size. VPI provides a simple quantitative representation of this proportional relationship. The observed association raises the hypothesis that a relatively lower injection density for a given gland size may increase the likelihood of subsequent retreatment. VPI is a derived variable calculated from prostate volume and the number of injections; therefore, it may be mathematically related to its components. Thus, VPI should be interpreted as a surrogate measure of injection density relative to gland size rather than an independent biological factor. The potential influence of collinearity should be considered when interpreting these findings.

Recent studies on minimally invasive surgical therapies (MIST) for BPH have highlighted the need to balance symptom relief with preservation of functional outcomes. Although MISTs are promising, they are not yet fully established as standard treatments for BPH, and uncertainties remain regarding their long-term durability and optimal patient selection [18]. For example, prostatic urethral lift has been shown to improve urinary symptoms while preserving ejaculatory function, underscoring the importance of patient-centered treatment strategies [19].

In this context, optimizing procedural approaches according to individual prostate characteristics represents an important clinical challenge. Our findings suggest that VPI may serve as a simple and practical parameter to support individualized injection planning in WVTT, beyond reliance on anatomical parameters such as urethral length. However, this potential clinical relevance should be interpreted cautiously until validated in larger independent cohorts.

The current study had several limitations that should be acknowledged. Given the limited number of events (n = 15), the multivariable model was intentionally restricted to avoid overfitting. Although additional clinically relevant variables such as age, prostate volume, baseline symptom severity, and retention history may act as confounders, these could not be included in the model. These factors may potentially influence both injection strategy and treatment outcomes. Therefore, residual confounding cannot be excluded, and the observed association between VPI and treatment failure should be interpreted with caution. This retrospective single-center study included a limited number of events, particularly re-surgeries, and the composite endpoint was largely driven by medication resumption. Individual failure components were not analyzed separately due to limited statistical power. In addition, a predefined VPI threshold was not established. Thus, the findings should be considered exploratory. Prospective validation in larger independent cohorts is required.

Conclusion

A higher VPI was associated with an increased risk of treatment failure after WVTT for BPH. These findings suggest a potential relationship between injection density relative to prostate size and treatment durability. However, given the exploratory nature of this single-center study and the limited number of events, the results should be interpreted with caution. Further validation in larger prospective cohorts is required.

Abbreviations

WVTT

Water vapor thermal therapy

VPI

Volume per injection

5-ARI

5-Alpha reductase inhibitor

BPH

Benign prostatic hyperplasia

LUTS

Lower urinary tract symptoms

PV

Prostate volume

PVR

Postvoid residual volume

PSA

Prostate-specific antigen

IPSS-QOL

International Prostate Symptom Score quality of life

HR

Hazard ratios

CI

Confidence intervals

IQR

interquartile range

Authors' contributions

TO conceptualized the study, collected and analyzed the data, drafted the manuscript, critically revised the manuscript, and approved the final version.

Funding

This study did not receive any funding.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to protection of participant privacy but are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was submitted to and approved by the Ethics Committee of Medical Corporation Koshin-Kai (approval number: KS1003). The requirement to obtain informed consent was waived by the Ethics Committee owing to the retrospective nature of the study. This study was conducted in accordance with the principles of the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.