WATER III: Aquablation achieves comparable outcomes to laser enucleation for BPH

Patients with benign prostatic hyperplasia (BPH) who underwent treatment with Aquablation achieved similar short-term symptom improvement to those who underwent transurethral laser enucleation of large prostates (LEP; 80 to 180 mL) while demonstrating lower rates of ejaculatory dysfunction and stress incontinence, according to 3-month data from the WATER III trial (NCT04801381).

Patients are expected to undergo follow-up for up to 5 years.

However, patients who underwent LEP demonstrated superior outcomes regarding prostate volume reduction and urinary flow rate improvement.

The data were presented by Manuel Ritter, MD, at the 40^th Annual European Association of Urology Congress in Madrid, Spain. Ritter explained that since the WATER I and WATER II trials, Aquablation has been adapted to improve bleeding rates seen in larger prostates through the integration of electrocautery. Laser enucleation, at the same time, has become a gold standard approach due to its benefits over simple prostatectomy, but the procedure comes with a steep learning curve.

“It was the logical consequence to test these 2 techniques [at] the highest level possible: a prospective trial with randomized patients,” he stated.

Thus, the WATER III trial enrolled 202 patients with BPH and a prostate size between 80 mL to 180 mL. The study included randomized and non-randomized cohorts.

“The Bayesian statistical model allows us to borrow strength from the randomized cohort to the non-randomized cohort,” Ritter explained. “The other patients not being willing to consent to randomization have been offered to be part of the non-randomized cohort.”

In the randomized cohort, 35 patients were randomly assigned to Aquablation, and 32 patients were randomly assigned to holmium/thulium LEP (HoLEP/ThuLEP). In the non-randomized cohort, 63 patients elected to undergo Aquablation, and 56 patients elected to undergo LEP. In total, 98 patients in the Aquablation arm and 88 patients in the LEP arm were treated.

Demographics of each cohort were largely similar across arms, with the only notable difference being in age. The mean age was 65.2 years among patients who underwent Aquablation vs 67.5 years among patients who underwent LEP (P = .02). The average duration of the procedure was 58.1 minutes in the Aquablation arm and 61.8 minutes in the LEP arm (P = .27).

Aquablation demonstrated non-inferiority to LEP regarding the study’s primary end point of mean change in International Prostate Symptom Score (IPSS). Specifically, the change in IPSS from baseline to 3 months was 12.9 in the Aquablation arm vs 13.1 in the LEP arm (mean delta, 0.86; 95% CI, -1.6 to 3.2; P = .745). In the Aquablation arm, the baseline IPSS was 20.7, which decreased to 9.1 at 3 months. In the LEP arm, the baseline IPSS was 21.5, which decreased to 9.3 at 3 months.

Regarding the study’s secondary end points, urinary flow rate improvement (Qmax) from baseline to 3 months was greater in the LEP arm (P < .0001). Patients in the LEP arm also saw a greater reduction in post-void residual (P = .2956). However, patients in the Aquablation arm achieved a greater reduction in prostate size (P < .0001).

Clavien-Dindo (CD) grade 2 or higher or persistent grade 1 adverse events were reported in 38.8% of patients in the Aquablation arm vs 54.5% of patients in the LEP arm (estimated mean difference, -10%; 95% CI, -34% to 13%; P < .05).

Ritter added, “Higher grade complications were rare in both groups, with 8.2% in the Aquablation group and 5.6% in the laser enucleation group. One patient had to stay for 1 night on ICU due to hypovolemia.”

Bleeding risk was comparable between both arms. However, patients in the Aquablation arm achieved superior outcomes regarding sexual function and urinary incontinence following surgery.

Specifically, ejaculatory dysfunction in the 3 months following surgery was reported in 14.8% of patients in the Aquablation arm vs 77.1% of patients in the LEP arm (P < .0001). Urinary incontinence was also lower in the Aquablation arm, with a rate of 8.7% compared with 20.0% among patients who underwent LEP (P = .0690). On this, no patients reported stress urinary incontinence in the Aquablation arm, compared with 9.1% of patients in the LEP arm (P < .05).

Ritter also noted, “Despite excluding UTI before surgery and giving antibiotic prophylaxis up to the standard of each study center, 29% of Aquablation patients and 24% of laser enucleation patients received antibiotic treatment during the 3 months after surgery.”

Patients included in this trial are expected to undergo follow-up for up to 5 years.

“The WATER III results are impressive, demonstrating that Aquablation therapy can achieve outcomes comparable to laser enucleation,” said Naeem Bhojani, MD, FRCSC, of the University of Montreal, in a news release on the findings.² “The consistent efficacy coupled with the significantly lower rates of ejaculatory dysfunction and stress incontinence represents a meaningful advancement for patients seeking treatment for BPH. The effectiveness of Aquablation therapy is shown by its ability to achieve similar results as highly skilled and experienced laser enucleation surgeons.”

REFERENCES

1. Ritter M, Stein J, Barber N, et al. WATER III: Aquablation vs. Transurethral laser enucleation of large prostates (80-180ml) in benign prostatic hyperplasia. Presented at 40^th Annual European Association of Urology Congress. Madrid, Spain. March 21-24, 2025. Abstract GC4

2. WATER III randomized-controlled trial results announced at European Association of Urology comparing Aquablation therapy to laser enucleation. News release. PROCEPT BioRobotics. Published online and accessed March 24, 2025. https://www.globenewswire.com/news-release/2025/03/24/3047778/0/en/WATER-III-Randomized-Controlled-Trial-Results-Announced-at-European-Association-of-Urology-Comparing-Aquablation-Therapy-to-Laser-Enucleation.html