Endoscopic necrosectomy has emerged as the preferred method for managing walled-off pancreatic necrosis. Despite the growing adoption of endoscopic techniques, there are limited comparative data with large sample sizes to guide the optimal timing and sequencing of interventions. This systematic review evaluated the efficacy and safety of upfront endoscopic necrosectomy (UEN) compared with step-up endoscopic necrosectomy (SUEN) in patients with walled-off pancreatic necrosis.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive search on MEDLINE, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov , for articles published from the inception of the databases to February 20, 2025. Random-effects meta-analytic models were used to calculate pooled relative risks (RRs) or standardized mean differences (SMDs) and their 95% CIs for dichotomous and numerical variables, respectively. Heterogeneity across studies was assessed using the I ² statistic and Cochran's Q test.

We included 5 studies with a total sample size of 548 participants (55.9% male and 44.1% female). Most of the included studies were retrospective comparative cohort analyses (4 of 5) and were conducted in the United States (4 of 5). The mean age of participants was 51.74 ± 15.4 years in the UEN group and 53.2 ± 18.0 years in the SUEN group. In terms of efficacy outcomes, we found no significant differences in clinical success (RR, 1.04; 95% CI, 0.98-1.11), technical success (RR, 1.27; 95% CI, 0.86-1.870), length of hospital stay (SMD, −0.03; 95% CI, −0.61 to 0.54), and number of interventions required to achieve clinical success (SMD, −0.04; 95% CI, −0.65 to 0.57), in patients receiving UEN compared with the SUEN group. Similarly, there were no significant differences in safety outcomes such as postprocedural bleeding (RR, 0.66; 95% CI, 0.34-1.30), postprocedural infection (RR, 1.06; 95% CI, 0.40-2.85), stent migration (RR, 0.46; 95% CI, 0.14-1.54), stent occlusion (RR, 0.42; 95% CI, 0.17-1.04), recurrence (RR, 0.71; 95% CI, 0.31-1.62), or postprocedure mortality (RR, 1.19; 95% CI, 0.48-2.97) between the 2 groups.

Our study demonstrates that UEN and SUEN perform similarly in terms of commonly measured efficacy and safety end points. This finding underscores the importance of an individualized approach in the treatment of patients with walled-off pancreatic necrosis.