Although EFTR has expanded therapeutic options for complex subepithelial and early neoplastic lesions, a significant unmet clinical need remains in European practice: achieving a safer, more reproducible, and standardized resection technique that is less dependent on operator experience and variability in center equipment. Current limitations and complication risks demonstrate that the existing EFTR model requires technological reinforcement.

The innovative contribution of this work is positioning hybrid EFTR approaches as a conceptual foundation for a “next-generation EFTR”- a technologically enhanced and methodologically standardized procedural model.

Full-thickness resection (EFTR) has expanded endoscopic options for complex subepithelial and early neoplastic gastrointestinal lesions. However, significant limitations remain in European practice: variability of technique between centers, differences in equipment availability, high dependence on operator experience, risk of perforation, and the need for surgical intervention in some cases.

ESGE Strategy 2025 highlights the need to improve safety, reproducibility, and standardization of advanced procedures.

These limitations emphasize the need for a technologically enhanced and methodologically standardized next-generation EFTR model.

Hybrid EFTR approaches combine full-thickness resection with additional endoscopic technologies, such as:

• advanced hemostasis modalities (advanced coagulation devices, vessel-sealing tools);

• enhanced defect closure systems (over-the-scope clips, full-thickness suturing systems, combined clipping);

• visual assist tools (optical magnification, digital filters, image stabilization);

• traction-assisted methods (suture-traction, clip-line traction);

• integration of EFTR with ESD- or STER-based elements to improve control of the resection layer.

These hybrid technologies are considered a pathway toward a safer, more standardized, and more reproducible EFTR model.

A structured review of PubMed, Embase, and Scopus literature (2018-2025) was performed, assessing EFTR for subepithelial and early neoplastic lesions of the stomach, small intestine, and colon.

Evidence shows that hybrid EFTR approaches contribute to:

    1.    Improved safety: Enhanced visualization, hemostasis, and closure tools provide more stable control of the resection field and reduce complications.

   2.    Higher R0 resection rates: Hybrid series report R0 rates consistently above 90%, comparable to or higher than standard EFTR.

   3.    Reduced inter-operator variability: Hybrid tools provide more predictable resection trajectories and easier defect closure.

    4.    Better reproducibility and training potential: Combined technologies support modular education following the ESGE “train-to-standard” concept.

   5.    Foundations for EFTR 2.0 registries: Several studies highlight the need for multicenter registries as a basis for future guideline development.

Hybrid endoscopic solutions have the potential to form the concept of EFTR 2.0 - a safer, more standardized, and more reproducible model for full-thickness resection in the gastrointestinal tract. They align with ESGE priorities by improving safety, visual control, complication reduction, and training standardization.

Contemporary evidence underscores the need for further prospective, multicenter studies aimed at establishing registries and developing standardized protocols under ESGE guidance.