Immediate versus Step-Up Endoscopic Necrosectomy after EUS-Guided Drainage of Walled-Off Pancreatic Necrosis: A Meta-Analysis of Randomized Trials

Abstract Endoscopic ultrasound (EUS)-guided drainage is now the preferred first-line treatment for walled-off pancreatic necrosis (WON). Necrotic tissue can be removed either at the time of initial drainage (immediate necrosectomy) or later, using a step-up approach if patients fail to improve. However, the optimal timing of necrosectomy remains unclear. We performed a systematic review and meta-analysis of randomized controlled trials to compare immediate versus step-up necrosectomy following EUS-guided drainage of WON. We systematically searched PubMed/MEDLINE, Embase, and Cochrane CENTRAL from inception through March 2026 for randomized controlled trials comparing immediate necrosectomy during index drainage with a step-up (on-demand) approach. The primary outcome was reintervention-free clinical success (RFCS), defined as resolution of the collection without the need for additional procedures. Secondary outcomes included overall treatment success, adverse events (disease- and procedure-related), number of necrosectomy sessions, length of hospital stay, and mortality. A random-effects meta-analysis was performed using risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs). Four randomized controlled trials, including 215 patients, were analyzed. Reintervention-free clinical success was significantly lower in the immediate necrosectomy group compared with the step-up approach (RR 0.07, 95% CI 0.02–0.25; I 2 = 0%). Overall treatment success, adverse events, and mortality were similar between the two strategies. However, immediate necrosectomy was associated with a substantially higher procedural burden, reflected by a greater number of necrosectomy sessions. These findings were consistent across sensitivity analyses. Performing necrosectomy at the time of initial EUS-guided drainage does not improve clinical outcomes and significantly reduces the likelihood of achieving success without additional interventions. A step-up approach, reserving necrosectomy for selected patients who do not improve after drainage, appears to be the more appropriate strategy. Future research should focus on identifying predictors of necrosectomy requirement to support a more individualized treatment approach.