Year 1, Year 2 and Year 3 Outcomes
Initial clinical experience was reported in 2016, and the technology obtained FDA clearance in 2017 after the publication of the WATER trial, a PHASE III multicenter international, double blind, randomized, non-inferiority study with 181 subjects comparing Aquablation® (116/181) to TURP (65/181).9 Men 45-80 years old with prostate size 30-80 cc (by TRUS), moderate-severe LUTS (International Prostate Symptom Score (IPSS) ≥ 12), and maximum urinary flow rate (Qmax) <15ml/s were included and stringent exclusion criteria applied. After randomization, although treatment was by an unblinded research team, a separate blinded team performed all follow-up. The primary endpoint was the change in the IPSS at 6 months; scores decreased by 16.9 points and 15.1 points for Aquablation and TURP, respectively (noninferiority p<.0001 and superiority p=0.1347). The primary safety endpoint was the proportion of subjects with adverse events, defined as Clavien-Dindo grade 2 or higher or any grade 1 with persistent disability. The 3-month primary safety endpoint rate was lower in the Aquablation group than in the TURP group (26% vs 42%, p = 0.0149). At 2 years, IPSS score improvement was sustained (14.7 in Aquablation and 14.9 in TURP (p=0.834, 95% CI for difference -2.1 to 2.6)), and Qmax improvement was large in both groups (11.2 and 8.6 cc/s for Aquablation and TURP, respectively (p = 0.1880, 95% CI for difference -1.3 to 6.4).10 Two-year reduction in post-void residual (PVR) was 57 and 70 cc for Aquablation and TURP, respectively (p = 0.3895). Prostate specific antigen (PSA) decreased significantly in both groups by 1 point (p < 0.01). Retreatment rates were 4.3% and 1.5% (p = 0.42) in the Aquablation and TURP groups, respectively. Among the subset of sexually active men without the condition at baseline, anejaculation was less common after Aquablation (10% vs. 36%, p=0.0003). When post-Aquablation cautery was avoided rates of anejaculation were lower (7% vs. 16%, p=0.1774), and this resulted in the reduced grade 1 persistent events found in the Aquablation group. The authors hypothesize that Aquablation avoids damage to tissues involved in ejaculation though precise, image-based targeting, and robotic execution. Limitations of the study include the risk of performance bias as surgeons were not blinded, and unknown generalizability to a broader population. Three-year results were essentially unchanged.4
Gilling PJ et al. (2022) published the 5-year follow-up data for the WATER study.20 Five-year follow-up revealed IPSS scores improved by 15.1 points in the Aquablation® group and 13.2 points in TURP (p = 0.2764). IPSS reduction was 3.5 points greater across all follow-up visits in the Aquablation® group compared to the TURP group (p = 0.0123) for men with larger prostates (≥50mL). Peak urinary flow rates for Aquablation® and TURP improved when compared to baseline (125% and 89% respectively). 12.3% of patients treated with TURP required a subsequent intervention compared to 6% of patients treated with Aquablation®, up to 5 years secondary to recurrent LUTS.
A 2019 Cochrane Review based on 1-year WATER trial results, found evidence of similar results with TURP to be of moderate-certainty related to the urologic symptom score (IPSS) primary outcome measure. All other metrics were graded low-certainty (QOL), to very low-certainly (adverse events, retreatments, erectile function, ejaculatory dysfunction).3 Evidence was downgraded mainly due to study limitations (performance, reporting, and attrition bias), and imprecision (confidence intervals that crossed the assumed thresholds of clinically important differences or few events, or both). For example, both sexual outcome (erectile and ejaculatory function) results were downgraded 2 levels for a combination of imprecision and study limitations (high risk of performance and attrition bias). The authors recommend larger, more rigorously conducted, and transparently reported, studies comparing Aquablation to other techniques (laser enucleation, prostatic urethral lift, robotic-assisted simple prostatectomy) for which there is also increasing interest.
In a study by Nguyen DD, Barber N, Bidair M et al.6 The authors looked to determine if the effectiveness of Aquablation is independent of prostate size by comparing its outcomes in 2 clinical trials. The first trial that was conducted was with men whose prostate was between 30 and 80 mL (WATER I) and the other trial was conducted with men whose prostates were between 80 and 150 mL (WATER II). Water I trial is a prospective, double-blind, multicenter, international clinical trial comparing the safety and efficacy of Aquablation and TURP as surgical treatments of LUTS due to BPH in men aged 45–80 years with a prostate volume between 30 and 80 mL, as measured by TRUS. Patients were enrolled at 17 centers. One hundred sixteen men participated. The Water II trial was a prospective, multicenter, international clinical trial of Aquablation for the surgical treatment of LUTS/BPH in men aged 45–80 years with a prostate volume between 80 and 150 mL, as measured by TRUS. Patients were enrolled at 13 US and 3 Canadian sites. One hundred one men participated. The studies parameters included patients who completed the IPSS. Patients completed questionnaires such as the Incontinence Severity Index (ISI), the International Index of Erectile Function (IIEF-5), and the Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD). Patients received uroflowmetry, PVR measurements and underwent standard laboratory blood assessment. These questionnaires and measurements were provided at baseline. PVR and lab test were required postoperatively at 1 and 3 months. Adverse events were rated by the clinical events committee as possible, probably or definitely related to the study procedure and were classified using Clavien–Dindo grade for 3 months after treatment. The inclusion and exclusion criteria were the same for both studies. The inclusion criteria included patients with moderate-to severe symptoms indicated by a baseline IPSS of ≥12 and a maximum urinary flow rate (Qmax) of <15 mL/s. Exclusion criteria included patients with a body mass index of ≥42 kg/m2, a history of prostate or bladder cancer, neurogenic bladder, bladder calculus or clinically significant bladder diverticulum, active infection, treatment for chronic prostatitis, diagnosis of urethral stricture, meatal stenosis or bladder neck contracture, a damaged external urinary sphincter, stress urinary incontinence, post-void residual urine volume (PVR) >300 mL or urinary retention. The comparison between the 2 studies revealed the mean operative time for WATER I was 33 minutes and 37 minutes for WATER II. The actual treatment time was 4 minutes (WATER I) and 8 minutes (WATER II). For International Prostate Symptom Score, the mean change at 12 months averaged 15.1 for WATER I and 17.1 for WATER II (P = 0.605). Clavien–Dindo grade ≥II events at 3 months mark occurred in 19.8% of WATER I patients and 34.7% of WATER II patients (P = 0.468).6 The authors conclude outcomes and effectiveness of Aquablation are comparable and are independent of prostate size with the expectation that with larger prostates a higher risk of complication is possible.
In an April 2020 publication of WATER II data in the Canadian J Urol, Desai et. al.5 report, 2 year safety and effectiveness of the Aquablation procedure for treatment with men with symptomatic benign prostatic hyperplasia (BPH) and large volume 80-150 cc prostates. The study provides strong evidence that Aquablation provides excellent mid-term (2 year) long-term relief of LUTS related to BPH. The study is notable in that enrolled men (target range 80-150 cc, mean 107 cc, 83% with a large median lobe), a group that typically cannot undergo TURP were included.
Bach et al (2020) conducted a prospective, multicenter, single-arm, open-label clinical trial (OPEN WATER) of Aquablation® therapy in 5 community-based sites.21 The study included 178 with the diagnosis of LUTS/BPH, aged 38–88 years with a prostate volume between 20 and 148 mL, as measured by TRUS. At baseline and at 3- and 12-month follow-up, patients completed the following: IPSS, Incontinence Severity Index, Pain Intensity Scale, Quality of Recovery Visual Analog Scale, International Index of Erectile Function (IIEF-15), the Male Sexual Health Questionnaire (MSHQ-EjD), uroflowmetry, and post-void residual (PVR) volume measurements. The IPSS decreased from 21.7 at baseline to 6.4 at the 12-month follow-up (p < 0.0001). The maximum urinary flow rate increased from 9.9 mL/s at baseline to 20.8 mL/s at month 12 (p < 0.0001). PVR improved from 108 mL to 47 mL at 3 months and 61 mL at 12 months. Ejaculatory function was relatively preserved. Prostate volume assessed with transrectal ultrasound decreased 36% by month 3. The authors concluded that “real-world” evidence (patients in a non-clinical trial setting) shows that the Aquablation® procedure is safe and effective for the treatment of symptomatic BPH.
A retrospective review of prospectively collected data by Kasraeian et al (2020) evaluated the safety and efficacy of Aquablation® in a community-based setting.22 The study included 55 patients treated between July 2018 and December 2019 with prostate size ranging from 27 to 252 mL in volume (mean of 100 mL). Patient ages ranged from 50 to 84 years. Results demonstrated a significant improvement in the mean IPSS of 17.2 points (p < 0.0001). By uroflowmetry, the mean Qmax improved from 7.4 mL/sec at baseline to 20.6 mL/sec postoperatively (p < 0.0001). Patients with prostate volume >100 mL had similar hospital length of stay, BPH symptom reduction, and Qmax improvement compared to patients with prostate volume <100 mL.
American Urological Association (AUA) amended guidelines now include Aquablation, but do not classify it as a minimally invasive surgical treatment (MIST) since general anesthesia is required. Based on 1-year WATER study results the AUA, found parity between Aquablation and TURP on IPSS, LUTS, and QOL scores (Quality of Evidence: Moderate). Their recommendation is: “Aquablation may be offered to patients with LUTS attributed to BPH provided prostate volume >30/<80g; however, patients should be informed that long term evidence of efficacy and retreatment rates remains limited. (Conditional Recommendation; Evidence Level: Grade C)”.11
Canadian Urological Association (CUA) 2018 guidelines also give a “conditional recommendation based on moderate-quality evidence” that Aquablation may be offered to men “interested in preserving ejaculatory function, with prostates <80 cc, with or without a middle lobe”.12
A 2018 National Institute for Health and Care Excellence (NICE) systematic review based on 6-month WATER results concluded the procedure should only be used with “special arrangements,” a defined designation meaning there are uncertainties about safety and effectiveness.13