Endoscopic and Hybrid Approaches for Gastric Subepithelial Tumors: Expanding the Frontiers of Minimally Invasive Therapy

Per-oral flexible endoscopy has expanded minimally invasive options for the management of gastric subepithelial tumors (G-SETs). This narrative review appraises conventional and advanced endoscopic resections alongside hybrid laparoscopic–endoscopic procedures, within a size- and layer-based clinical framework. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) achieve high en bloc resection rates for small, intraluminal tumors arising from mucosa or submucosa. Traction strategies and dedicated traction devices may improve submucosal exposure, shorten procedure time, and reduce adverse events. Submucosal tunneling endoscopic resection (STER) has been developed to enucleate tumors originating from the muscularis propria while preserving mucosal integrity. However, tunnel creation and specimen retrieval become challenging for large tumors or for those located in the cardia or fundus. Endoscopic full-thickness resection (EFTR) enables controlled transmural excision of G-SETs arising from deeper wall layers. Exposed EFTR, combined with secure endoscopic closure, provides high en bloc and complete (R0) resection rates. Closure options range from through-the-scope clips—for small defects—to over-the-scope clips, endoloop-clip purse-string methods, reopenable-clip over-the-line techniques and endoscopic suturing systems—for larger defects. Non-exposed EFTR and device-assisted systems reduce the risk of peritoneal contamination, although complete resection rates are more variable. Hybrid approaches, including classical laparoscopic–endoscopic cooperative surgery (LECS) and non-exposure variants, combine endoscopic precision with the safety and closure capabilities of laparoscopic surgery, minimizing the amount of resected gastric wall. They are particularly suited to larger, awkwardly located or ulcerated G-SETs. Emerging traction platforms, flexible robotic systems, and AI-based tools may further broaden the role of per-oral flexible endoscopy for the treatment of G-SETs. However, evidence remains preliminary, and surgery continues to play a key role for large, extraluminal or anatomically prohibitive G-SETs.