Safety and Efficacy of Fluoroscopy-Free Technique During Retrograde Intrarenal Surgery for Renal Stones: A Prospective, Randomized, Controlled, Noninferiority Trial

<b><i>Purpose:</i></b> Fluoroscopy-free (FF) retrograde intrarenal surgery (RIRS) presents a promising alternative to fluoroscopy-guided (FG) RIRS to reduce radiation exposure in endourology. This study aimed to assess the noninferiority of FF-RIRS compared with FG-RIRS regarding safety and efficacy. <b><i>Patients and Methods:</i></b> A prospective, randomized trial was conducted at a tertiary care center from November 2021 to June 2024. Adult patients with renal stones (10-30 mm) eligible for RIRS were randomized to either the FF-RIRS group (direct endoscopic visualization) or the FG-RIRS group. The primary endpoint was the stone-free rate (SFR), with secondary outcomes including stone size reduction, fluoroscopy use in FF-RIRS, operative time, hospital stay, reintervention, and complication rates. <b><i>Results:</i></b> The final analysis included 253 patients in the FF-RIRS group and 249 in the FG-RIRS group. The mean age was 41.3 ± 12.3 years, and the mean stone size was 16.5 ± 3.2 mm. In the FF-RIRS group, 214 procedures (84.6%) were performed without fluoroscopy, whereas 39 (15.4%) required fluoroscopy because of intraoperative challenges. Regression analysis identified multiple stones and congenital renal anomalies as predictors for fluoroscopy use. SFRs were comparable between groups (zero residual fragments [RF]: 54.9% vs. 51.0%, no RF >2 mm: 70.4% vs. 69.1%, no RF >4 mm: 79.4% vs. 82.3%) (<i>p</i> > 0.05). For SFR defined as no RF >4 mm, FF-RIRS demonstrated noninferiority with a -10% margin (p = 0.021). Furthermore, per-protocol analysis confirmed noninferiority (<i>p</i> = 0.002), with nearly equal SFRs (82.7% vs. 82.3%, <i>p</i> = 0.914). Stone size reduction, operative time, hospital stay, reintervention, and complication rates were similar between groups, with no serious adverse events. <b><i>Conclusions:</i></b> FF-RIRS is a safe and effective alternative to FG-RIRS for selected patients. Its safety and efficacy are noninferior to FG-RIRS in direct comparison. However, fluoroscopy should remain available as a backup, especially in complex cases, to ensure optimal outcomes and patient safety.