194 The WATER Study Sexual Function Results – A Phase III blinded randomized parallel group trial of Aquablation vs. Transurethral Resection of the Prostate with Blinded Outcome Assessment for Moderate-to-Severe LUTS in men with Benign Prostatic Hyperplasia

Abstract

Prostate resection for patients with LUTS remains the gold standard for surgical treatment of BPH. However, as many as two-thirds of men will suffer from sexual dysfunction, primarily ejaculatory dysfunction. We aimed to compare the sexual function outcomes of prostate ablation using a high-pressure waterjet (A) vs. mono- or bipolar electrocautery resection (T). In this randomized, blinded, multicenter phase III trial, men with moderate-to-severe LUTS related to BPH were assigned to transurethral resection of the prostate using either standard electrosurgery (TURP) or robotically-assisted waterjet ablation (Aquablation). The trial has a co-primary safety and efficacy endpoint designed to show non-inferiority regarding efficacy. The primary safety endpoint was the occurrence of Clavien-Dindo Grade 1 (persistent ejaculatory dysfunction, erectile dysfunction, or urinary incontinence) or Grade 2 or higher operative complications at 3 months. The primary efficacy endpoint was the reduction IPSS score at 6 months. The geographic enrollment from the International and US sites was 91 and 93 subjects, respectively. The mean baseline IPSS score (T: 22.2 vs. A: 22.9, p=0.43), demographic profile, and mean prostate volume (T: 52 mL vs. A: 54 mL, p=0.31) were similar in both arms. Mean operative time was equivalent between the two groups (T: 35.5 vs. A:32.8 minutes, p=0.28), but mean resection time was significantly lower in the Aquablation group (28 vs. 4 minutes, p<.0001). The primary safety endpoint (Clavien-Dindo grade 1 persistent or grade 2 or higher event in the first 3 months) occurred in 29 Aquablation subjects (25.0%) and 26 TURP subjects (40.0%). The rate difference (Aquablation – TURP) was -15.0%, with a 95% CI of -29.2 to -1.0%, therefore demonstrating superiority of Aquablation versus TURP. The difference in primary endpoint safety rate was driven primarily by retrograde ejaculation. Of men who were sexually active at both baseline and the study visit, persistent retrograde ejaculation in the first 6 months occurred in 8 Aquablation subjects (11.3%) and 16 TURP subjects (36.4%). The rate difference (Aquablation – TURP) was -25.1%, with a 95% CI of -41.2 to -9.6%. The upper confidence limits was less than the zero, demonstrating superiority of Aquablation versus TURP. Amongst men who were sexually active at both baseline and study visits, the quality and quantity of ejaculate (as measured by MSHQ-EjD) increased slightly but not significantly from baseline levels in the Aquablation group but decreased by approximately 2 points in the TURP group (p < 0.02). A repeated measures analysis of variance showed a mean difference of 3.2 points in change scores (p<.001). MSHQ-EjD bother scores remained at baseline levels for Aquablation and were somewhat decreased for the TURP group. The difference in bother change scores was statistically significant at month 3 only. IIEF-5, which measures the quality of erections, showed no changes from baseline in either group. Mean IPSS scores decreased from 22.9 at baseline to 5.9 at 6 months in the Aquablation group and from 22.2 at baseline to 6.8 in the TURP group. The IPSS change score at month 6 was 1.8 points larger after Aquablation (95% CI -0.4 to 4.0); therefore, demonstrating non-inferiority.