Introduction

As men age, the number with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) steadily increases [1]. There are many surgical treatments for those with small-to-moderate prostate volumes. However, surgical options for treating larger prostates are limited. Simple prostatectomy is a very common procedure utilized, which is effective in improving LUTS symptoms while having a lower rate of reoperation compared with TURP [2,3,4]. A caveat to this procedure is it requires abdominal surgical incisions and carries a higher risk of bleeding and longer hospital stay and catheterization times [5].

Advanced minimally invasive endoluminal techniques such as holmium enucleation of the prostate (HoLEP) have evolved to enable treatment of larger prostates transurethrally but its penetrance has remain limited because of a relatively significant learning curve (> 50 cases and often fellowship training) and prolonged operative time [6, 7]. Alternatively, GreenLight XPS (Boston Scientific, Marlborough, MA, USA) photoselective vaporization (PVP) has been used to treat patients with large glands but again requires a steep learning curve. There have been some data to demonstrate a higher retreatment rate for very large prostates [8]. Recently, Aquablation has emerged as a novel BPH treatment that integrates real-time ultrasound imaging with a robotically executed surgeon-guided waterjet to resect prostate tissue. Early studies demonstrated high levels of efficacy with low risks of sexual side effects [9, 10].

We sought to determine the short-term safety and efficacy of Aquablation in men with LUTS due to BPH with large prostate volumes.

Methods

Trial Design and Participants

This pooled analysis draws upon United States patients from two contemporary IDE clinical studies called WATER (NCT02505919) and WATER II (NCT03123250). Both studies were prospective multicenter trials with similar inclusion such as LUTS due to BPH in males 45–80 years of age, baseline International Prostate Symptom Score (IPSS [11]) ≥ 12 and a maximum urinary flow rate (Qmax) < 15 ml/s. The differences were in the allowable prostate sizes. For this pooled analysis, subjects with 60–150 cc prostates were the target population. This includes all prostates treated in the US ≥ 60 cc. Both studies were performed with Institutional Review Board approval from each participating institution, and all participants provided informed consent using study-specific forms prior to any test that went beyond standard care.

At baseline, subjects completed the IPSS as well as several validated questionnaires (Incontinence Severity Index, Pain Intensity Scale, International Index of Erectile Function (IIEF-5 [12]), the Male Sexual Health Questionnaire (MSHQ-EjD [13]), uroflowmetry and post-void residual (PVR) volume measurements and underwent standard laboratory blood assessment. Questionnaires, uroflowmetry, PVR and laboratory tests were also required at selected postoperative visits. Ejaculatory function was defined as subjects who are sexually active (at baseline and follow-up visits) with a baseline ejaculatory function score of 1 (some ejaculate) or greater based on his response to MSHQ-EjD question 3 and the post-treatment response changes to zero (could not ejaculate). Erectile dysfunction was defined as subjects who had normal erectile function at baseline (SHIM score of 22–25) and a post-treatment response of moderate-to-severe ED (SHIM score of 11 or less).

Description of Technique

The preoperative preparation of the patient follows the same routine as preparing for a transurethral resection of the prostate (TURP). Once in the operating theater, the patient is placed in the lithotomy position where general or spinal anesthesia is used. Aquablation was performed using the AquaBeam System (PROCEPT BioRobotics, Redwood Shores, CA, USA). As previously reported [14], a 24-F handpiece probe similar to a rigid cystoscope is inserted into the prostatic urethra and secured using a bed-mounted rigid arm. With real-time prostate visualization using a BK Ultrasound bi-plane transrectal ultrasound (Analogic, Boston, MA, USA), the surgeon uses a console to mark the target resection contour. Under the surgeon’s control, the ablation of tissue is robotically executed using a high-velocity waterjet to resect adenomatous tissue while avoiding the verumontanum and ejaculatory ducts. Following Aquablation, tissue samples can be collected for histopathology. Post-treatment management is done by inserting a standard urinary catheter, typically left in overnight, with bladder neck traction applied with continuous bladder irrigation. The patient recovery process is comparable to that with TURP.

Follow-Up

After discharge from the hospital, patients had follow-up visits at 1 and 3 months.

Data and Study Monitoring

Study data were entered into an electronic data capture system by site coordinators and were monitored and source-verified. Adverse events were collected throughout follow-up and evaluated by an independent clinical events committee. The data-monitoring committee reviewed safety data monthly until the completion of study primary endpoint analysis.

Statistical Analysis Method

T tests for continuous variables and Fisher’s test for ordinal/binary variables were used. All statistical analysis was performed using R [15].

Compliance with Ethics Guidelines

All procedures performed to gather the data presented here were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Results

One hundred seven patients with 60–150 cc prostate size were included in this pooled analysis. One hundred four (97%) patients completed the 3-month follow-up visit. Of the three missed visits, one subject withdrew consent, one subject missed the visit because of the holiday schedule, and one subject missed the visit because of AE recovery. Baseline characteristics are summarized in Table 1. Mean age was 67.3 ± 6.5 and baseline IPSS 23.4 ± 6.5 points. Prostate volume ranged from 61 to 150 cc with a mean volume of 99.4 ± 24.1 cc. A middle lobe was present in 77.6% of cases.

Table 1 Baseline characteristics (n = 107)
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Mean operative time, defined as handpiece placement until the final urinary catheter placement, was 35.6 ± 14.9 min. The mean Aquablation resection time ranged was 7 ± 3.3 min. The average length of stay following the procedure was 1.6 ± 1 days. Most patients (62%) were discharged home with a catheter. Hemoglobin levels decreased from a mean of 14.9 ± 1.3 g/dl at baseline to 12.1 ± 2.2 g/dl postoperatively (drop of 2.9 g/dl, p < 0.0001).

The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown of Clavien-Dindo (CD) events resulted in 18% grade 2 comprised primarily of hematuria or clot retention requiring catheterization and urinary tract infections. The rate of grade 3 or higher events was 19% comprised primarily of hematuria or clot retention requiring intervention and meatal stenosis requiring intervention. One patient had a Clavien-Dindo 4b complication because of a cerebrovascular accident the following day postoperatively that evolved into multiorgan failure. The CD grade 1 persistent events consisted of ejaculatory dysfunction, incontinence and erectile dysfunction occurring in 11.2% of men (ejaculatory dysfunction n = 7, incontinence n = 3, ejaculatory dysfunction and incontinence n = 2). The incontinence events were a combination of mixed and urge incontinence. No erectile dysfunction events were reported. The rate of transfusions following Aquablation and prior to discharge was 5.6% requiring an average of 2.2 units per transfusion.

Mean baseline IPSS was 23.4 ± 6.5 points with a change at 3 months of 6.7 ± 4.9 points (drop of 16.7 points, p < 0.0001). The baseline IPSS quality of life was 4.7 ± 1 points and improved by 3 ± 2 points at 3 months. Uroflow parameters showed significant improvement at 3 months for both Qmax and PVR. Mean baseline Qmax was 8.9 ± 3.1 ml/s and increased to 19.6 ± 12.4 ml/s. Mean PVR baseline was 114.5 ± 111.2 ml and reduced to 49.7 ± 57.3 ml. Mean prostate volume reduction at 3 M based on TRUS was 38.3 ± 24.2 cc. Figure 1 shows the plot of efficacy data over time.

Fig. 1
figure 1

One- and 3-month functional outcomes following Aquablation in 82 males with LUTS/BPH and large prostates, IPSS, IPSS QOL, Qmax, PVR. *Statistical significance compared with baseline. ++Statistical significance compared with 1 month

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Discussion

We found the Aquablation technique to be safe and efficacious up to 3-month follow-up in males with prostate volumes ranging from 60 to 150 cc [16, 17]. Furthermore, IPSS, Qmax and PVR all showed significant improvement commensurate with optimal prostate tissue resection.

Gilling et al. evaluated a blinded randomized trial of Aquablation vs. TURP in 30–80-cc prostates, Aquablation had equivalent overall efficacy with a noteworthy reduction of retrograde ejaculation compared with TURP (10 vs. 36%; p = 0.0003) [14]. In a subgroup of larger (50–80 cc) prostates, Aquablation provided superior symptom-reduction efficacy in IPSS scores compared with TURP. Additionally, the WATER II study, a single arm trial, showed a promising safety profile in 80–150 cc prostates [18]. Both studies showed the feasibility and safety of the Aquablation technology. Complication rates were low across both groups, with resolution within 1 month postoperatively [18].

Current options available for men with BPH with large prostates are typically simple prostatectomy or transurethral enucleation using holmium, thulium or GreenLight lasers. However, these procedures have a high rate of morbidity and often result in longer hospital stay, longer operating times and a steeper learning curve. The 5% urinary incontinence (including both urge and stress incontinence) rate at 3 month for Aquablation was anticipated given the transient urinary incontinence rates reported for TURP and HOLEP of 39–44% [19].

We found the average length of stay for patients receiving Aquablation to be 1.6 days. This is substantially lower compared with other BPH procedures such as simple prostatectomy [3, 20] and PVP [21] and similar duration compared with HoLEP [20]. Gratzke et al. evaluated the early postoperative complications of open prostatectomy (OP), laparoscopic prostatectomy (LP) and HoLEP. They found the mean hospital stay was 5–12 days for patients in the OP group, 2–5.1 days for the LP groups and 1.2–2.7 days for the HoLEP group [20]. Another study examining the national trends of perioperative outcomes and risk factors of simple prostatectomy (SP) found the median length of stay following SP was 4 days (interquartile range 3–6) [3]. Lanchon et al. evaluated PVP and OP. They found the mean hospital stay for OP was 8 days and for PVP was 5 days [21].

A major advantage of the Aquablation procedure compared with other BPH procedures is its time efficiency. Operative time in this pooled analysis is at least half that reported for simple prostatectomy [20], PVP [21] and HoLEP [22]. In the present study of 60–150 cc prostate volumes, we found the mean operative time to be approximately 36 min. In a sub-analysis, patients with an average volume of 107 cc (all prostates > 80 cc) had a 4-min longer mean operative time compared with those with a mean average volume of 54 cc (all prostates < 80 cc). We believe this suggests that as the size of the prostate increases, the mean operative time increases minimally. This is in direct contrast to other procedures such as HOLEP and TURP where a larger prostate leads to an even larger increase in the operating time. In a study by Persu et al [23] evaluating TURP and open prostatectomy, they found the mean operating time for TURP to be 50 min (40–75) and for open surgery to be 65 min (45–85). Further, operative times for HoLEP have been as high as 62.1 min when removing approximately 40 g prostatic tissue [24].

The primary risk of treating large prostates is bleeding. The risk is driven by the longer operative time and more complex anatomy. Aquablation showed that with a 36-min operative time there was a transfusion rate of 5.6%. HOLEP procedures yield very low intraoperative transfusion rates (< 2%) [25] even though the procedure times can be lengthy. The transfusion rate for a simple and laparoscopic prostatectomy has been reported as high as 29% (range 12–29) [3, 20, 22]. A low perioperative transfusion rates of 4% has been reported for PVP [21], and it is an option for treating large-volume BPH. However, one must consider the rate of intraoperative TURP conversations, which has been reported to be in the range of 4–16% [8, 26] and increases as the prostates become larger. Aquablation has an advantage over PVP and OP with a near HOLEP-like transfusion rate profile.

There are some limitations associated with the present study. First, the follow-up time is short and limits the functional durability of the procedure on a long-term basis. Another limitation is the WATER II study was a single-arm trial without a control group unlike the WATER study. Additionally, the incontinent events were not descriptive enough to determine the difference between urge and mixed in the database. A strength of the study is the inclusion of patients with a wide range of larger prostate volumes. Additionally, limited current data are available on simple prostatectomy for retrospective comparison; however, one of the largest (35,171 patients) was utilized as a reference in this manuscript [3]. Additionally, standardized reporting of events categorized by Clavien-Dindo grades was limited in the literature.

Conclusions

The Aquablation procedure was safe and effective in patients with prostate measuring 60–150 cc. There were improvements in IPSS, Qmax and PVR at 3 months postoperatively in patients suffering from LUTS due to BPH.