WATER III: A Prospective, Partially Randomized Trial of Aquablation Therapy Versus Transurethral Laser Enucleation of the Prostate for Treatment of Lower Urinary Tract Symptoms

BACKGROUND AND OBJECTIVE: Aquablation and laser enucleation of the prostate (LEP) are treatments for alleviation of lower urinary tract symptoms (LUTS) that have not yet been directly compared in a prospective randomized trial. This study was designed to evaluate these treatments in terms of LUTS improvement and safety in men with large prostates. METHODS: WATER III is an investigator-initiated, international, multicenter, nonblinded, prospective noninferiority trial that includes randomized and nonrandomized participants. Eligible patients had moderate to severe LUTS and a large prostate volume (80-180 ml). The primary efficacy endpoint was the change in International Prostate Symptom Score (IPSS) from baseline to 3 mo. The primary safety endpoint was the incidence of Clavien-Dindo (CD) grade ≥2 or persistent CD grade 1 complications that had not resolved by 3 mo. Bayesian analyses were used to assess noninferiority. KEY FINDINGS AND LIMITATIONS: A total of 202 men were enrolled in the study, of whom 186 underwent surgery (98 Aquablation, 88 LEP). At 3 mo, data were available for 170 patients, including 66 randomized and 104 nonrandomized men. Both treatments showed similar mean IPSS improvement at 3 mo: -12.9 ± 6.9 with Aquablation versus -13.1 ± 7.5 with LEP, with an estimated difference of 0.93 (95% credible interval [CrI] -1.48 to 3.53) and noninferiority probability of >0.999. The incidence of CD grade ≥2/persistent grade 1 complications was 40.8% in the Aquablation group versus 56.8% in the LEP, with an estimated difference of -9.4% (95%CrI -31.8% to 12.9%; noninferiority probability 0.952). Retrograde ejaculation was less frequent after Aquablation (14.8% vs 77.1%; p < 0.001). Persistent stress urinary incontinence (SUI) was absent following Aquablation versus 9.3% after LEP (p < 0.05). CONCLUSIONS AND CLINICAL IMPLICATIONS: Aquablation demonstrated noninferior short-term LUTS relief and similar safety compared to LEP, with superior ejaculation preservation and avoidance of SUI in short-term follow-up.