Efficacy, safety, and cost of immediate versus on-demand endoscopic necrosectomy in infected necrotizing pancreatitis: a systematic review and meta-analysis

Background: Endoscopic ultrasound (EUS)-guided drainage is the standard of care for walled-off necrosis (WON); however, the optimal timing of subsequent endoscopic necrosectomy remains uncertain. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing immediate versus on-demand necrosectomy following EUS-guided drainage. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library through March 2026 for RCTs comparing immediate (≤ 72 h) versus on-demand necrosectomy in adults with necrotizing pancreatitis. Primary outcomes were technical success, clinical success, and the proportion of patients undergoing necrosectomy. Secondary outcomes included length of hospital stay, costs, need for percutaneous or multigate drainage, and adverse events. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Results: Four RCTs comprising 215 patients, of whom 192 (89.3%) had WON, were included. Immediate and on-demand approaches demonstrated similar technical success (RR 1.01, 95%CI 0.98–1.05) and clinical success (RR 1.17, 95%CI 0.98–1.40). Immediate necrosectomy was associated with a higher proportion of patients undergoing necrosectomy (RR 1.65, 95%CI 1.13–2.41). No significant differences were observed in length of hospital stay, costs, need for additional drainage, procedure- or disease-related adverse events, mortality, bleeding, stent migration, or pneumoperitoneum. Conclusions: Immediate endoscopic necrosectomy did not demonstrate a consistent clinical advantage over an on-demand approach. Low- to very-low-certainty evidence suggests little or no difference in clinical efficacy or safety outcomes, while very-low-certainty evidence suggests that immediate necrosectomy may increase the proportion of patients undergoing necrosectomy. However, the magnitude and clinical significance of this effect remain uncertain. These findings should be interpreted cautiously given the limited number of randomized trials, modest sample sizes, and low or very low certainty of evidence for several outcomes. Trial registration: This study was prospectively registered in PROSPERO (CRD420261366884).