Is salvage treatment necessary after incomplete resection of rectal neuroendocrine tumors: A systematic review and meta-analysis

Abstract

Background: Incomplete resection of rectal neuroendocrine tumors (NETs), defined by positive or indeterminate margins or lymphovascular invasion, raises concerns regarding residual disease and recurrence. However, the benefits of salvage treatment in these cases remain unclear.

Aim: To evaluate the oncologic impact of salvage treatment compared with observation after incomplete endoscopic resection of rectal NETs through a systematic review and meta-analysis.

Methods: We conducted a systematic review and meta-analysis in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. MEDLINE, EMBASE, and the Cochrane Library were searched from their inception until May 2025. Eligible studies included patients with incompletely resected rectal NETs managed with salvage treatment or observation, reporting outcomes of residual tumors or recurrence. Pooled estimates were calculated using random-effects models with Hartung-Knapp adjustments.

Results: Thirty-four studies with 2279 cases of incomplete endoscopic resection met the inclusion criteria. The incomplete resection rates differed markedly according to the initial resection method (17 studies): 73.1% for cold snare polypectomy, 29.8% for conventional endoscopic mucosal resection (EMR), 28.4% for modified EMR, and 14.7% for endoscopic submucosal dissection. Among the 19 studies that evaluated salvage treatment, the pooled residual tumor rate was 25.0% [95% confidence interval (CI): 12.0%-40.0%]. The crude recurrence rates from 31 studies favored salvage treatment over observation (0.96% vs 2.96%, P = 0.003). However, a meta-analysis of nine comparative studies found no statistically significant difference in recurrence risk (odds ratio = 0.89; 95%CI: 0.40-2.02).

Conclusion: Given the relatively high residual tumor rate and low incidence of recurrence, salvage treatment may be justified as both a diagnostic and therapeutic approach after incomplete resection of rectal NETs. Although its benefits in preventing recurrence remain unclear, clinical decisions should be individualized, as these findings are based on low-certainty evidence.

Keywords: Neuroendocrine tumors; Observation; Rectum; Residual neoplasm; Salvage therapy.