Endoscopic resection for esophageal gastrointestinal stromal tumors: Balancing R0 resection and long-term outcomes

Abstract

Xu et al retrospectively assessed endoscopic resection (ER) for esophageal gastrointestinal stromal tumors (E-GISTs) and reported excellent 5-year survival rates. Although ER shows promise as a minimally invasive procedure, the 75% R0 resection rate with recurrence observed even after R0 resection warrants further discussion. We highlight the need for careful patient selection based on tumor size, location, and risk, considering endoscopic and thoracoscopic approaches. Future studies should refine ER techniques, optimize patient selection, and establish long-term follow-up to guide E-GIST management.

Key Words: Endoscopic resection; Esophagus; Gastrointestinal stromal tumors; Recurrence; R0 resection

Core Tip: Xu et al highlighted the potential of performing endoscopic resection (ER) for esophageal gastrointestinal stromal tumors (E-GISTs). However, the 75% R0 resection rate raises concerns. Although ER offers a minimally invasive access, recurrence after R0 resection underscores the need for careful patient selection. Future studies should refine ER techniques; identify optimal candidates based on tumor size, location, risk, and genetics; and develop algorithms for treatment selection. Long-term follow-up is essential for assessing recurrence and ultimately guiding evidence-based E-GIST management.

TO THE EDITOR

We read with great interest the article by Xu et al, published in the World Journal of Gastroenterology, which retrospectively evaluated the outcomes of endoscopic resection (ER) for esophageal gastrointestinal stromal tumors (E-GISTs)[1]. This study reported a 5-year overall survival rate of 100% and a disease-free survival rate of 90.6% after ER, highlighting the potential of this minimally invasive approach for managing E-GISTs. However, the reported R0 resection rate of 75% raises important concerns regarding the long-term risk of recurrence and emphasizes the need for well-defined selection criteria to optimize endoscopic treatment outcomes.

Indications for endoscopic treatment

Based on the findings of Xu et al[1], careful consideration of the appropriate indications for endoscopic treatment of E-GISTs is warranted. Factors such as tumor size, tumor location, and risk stratification are critical for guiding treatment selection. For smaller tumors (typically ≤ 40 mm), endoscopic approaches such as endoscopic submucosal tunneling dissection (ESTD)[2], per-oral endoscopic tumor resection (POET)[3], submucosal tunneling ER (STER)[4,5], and ligation-assisted endoscopic enucleation (EE-L)[6] may offer advantages owing to their minimally invasive nature and potential for expedited recovery[7-9]. The ESTD and STER procedures involve creation of a submucosal tunnel to access and resect tumors originating from the muscularis propria, allowing En bloc resection while preserving the mucosal layer. The approach for POET is similar, but it was initially adapted from procedures developed for achalasia and focuses on full-thickness resection through the submucosal tunnel. EE-L is generally reserved for small lesions and involves unroofing the mucosa, followed by snare resection and ligation of the tumor base. Careful selection of patients is of paramount importance in clinical practice. Tumors smaller than 40 mm, located in the mid-to-lower esophagus, and exhibiting low-risk features on imaging and EUS, are generally considered suitable for ER. For tumors abutting critical structures or those with signs of muscularis propria invasion, a thoracoscopic or hybrid approach may be safer. Intraoperative complications such as bleeding or perforation, although rare, require immediate recognition and endoscopic or surgical management. Procedural modifications, including tunnel creation techniques, traction methods, and closure strategies continue to evolve and contribute to safer and more complete resections. However, for larger tumors or those located in anatomically challenging areas, a thoracoscopic approach, potentially with robotic assistance, may be a safer and more effective option[10-13]. Hybrid approaches such as combined thoracoscopic and endoscopic surgery may also be considered for tumors in anatomically complex locations[14,15]. Although enucleation is traditionally considered a surgical technique, it remains a viable option for smaller E-GISTs. Compared with surgical resection, endoscopic treatment is attributed to shorter hospital stays, faster recovery, and lower procedural costs. However, surgical approaches, such as enucleation or esophagectomy, may offer more consistent oncologic margins, especially for larger or high-risk tumors. Although quality-of-life assessments generally favor endoscopic methods owing to their less invasive nature, prospective studies directly comparing the long-term outcomes, recurrence rates, and cost-effectiveness between endoscopic and surgical treatments are still limited and warranted.

Operator experience is an important determinant of successful ER. Studies have shown that proficiency in techniques, such as ESTD or STER, often requires a considerable number of supervised procedures. Institutions aiming to implement ER for E-GISTs should ensure structured training programs and volume-based credentialing to maintain high safety and efficacy standards.

ER margins and long-term recurrence risk

Despite achieving R0 resection in low- or very low-risk GISTs, recurrence was observed in two of three cases, raising concerns about the limitations of current risk stratification systems and the interpretation of R0 resection in E-GISTs. R0 resection, defined histologically as the absence of tumor cells at the margin, is the goal of surgical management of GISTs and typically indicates curative resection[16]. However, the clinical significance of the resection margin width remains controversial, although a 1-mm margin is generally accepted under United Kingdom guidelines[17].

Interestingly, a large retrospective multicenter European study reported a significantly higher rate of R1 resections following enucleation (45.5%) compared with that for esophagectomy (7.7% R1/R2)[13]. R1 resection, defined as the microscopic presence of tumor cells at the margin, is often considered non-curative and is associated with an increased risk of recurrence[18]. However, several studies have also reported lower recurrence rates after enucleation, despite the higher R1 rate attributed to the selection of smaller lower-risk tumors for this approach[13,19]. This highlights a potential bias in interpreting the R0 resection status without accounting for tumor biology and clinical context. Furthermore, the European Society for Medical Oncology guidelines allow the acceptance of R1 margins in low-risk GISTs located in anatomically unfavorable areas after consultation with the patient[20].

Furthermore, the two recurrences observed in R0-resected, low-risk, and very low-risk GISTs in the present study suggest that factors beyond margin status may influence recurrence. These may include the inherent biological aggressiveness of the tumor, which is not always fully captured by current risk stratification systems that rely primarily on tumor size and mitotic count[21]. Current systems primarily rely on tumor size and mitotic index but may not adequately reflect the underlying biological behavior or aggressiveness of the tumor. Future models should consider incorporating molecular and genetic features, such as KIT and PDGFRA mutations, to improve predictive accuracy. To improve clinical decision-making, pathological reports should consistently include tumor size, location, mitotic index, and resection margin status. Furthermore, the identification of KIT and PDGFRA mutations may aid in assessing tumor behavior and guide the intensity of postoperative surveillance or consideration of adjuvant therapy. The precision and thoroughness of the surgical technique, particularly in achieving complete removal of the tumor pseudocapsule, may also affect recurrence. Additionally, the potential for sampling error during pathological assessment, leading to underestimation of the mitotic count or failure to identify microscopic extension beyond the apparent tumor margin, cannot be excluded.

Given these considerations, the high R0 resection rate observed in this study should be interpreted with caution. Although ER offers a minimally invasive approach for E-GISTs, achieving true oncologic clearance as reflected by long-term recurrence-free survival remains paramount. A standardized follow-up protocol may include endoscopic and/or cross-sectional imaging [e.g., computed tomography (CT) or endoscopy] every 6–12 months during the first 5 years, followed by annual monitoring up to 10 years, depending on the tumor risk profile. Criteria for recurrence should include tumor regrowth at the resection site, new submucosal lesions, or progressive changes in regional lymph nodes.

This study had several limitations. The conclusions are partly constrained by the limitations of existing literature, including small sample sizes in some studies and limited availability of long-term follow-up data. Standardized long-term surveillance protocols, including recommended intervals, imaging modalities, and criteria for recurrence detection, should be developed to improve consistency across studies and guide post-treatment monitoring. Furthermore, the current risk stratification systems may not fully capture the biological aggressiveness of E-GISTs, and the interpretation of R0 resection remains complex. Endoscopic techniques are constantly evolving, making long-term technical assessment challenging. Although this letter provides a general overview of endoscopic techniques, it does not provide detailed technical descriptions. Future research should address these limitations by including larger studies, refining risk assessment models, and incorporating more in-depth statistical analyses. Because this letter is based on a narrative review of the existing literature, no original statistical analysis was conducted. Future prospective studies applying standardized data collection and multivariate analyses are crucial to validate the current hypotheses and improve clinical decision making.

CONCLUSION

Xu et al[1] demonstrated that ER is a safe and effective alternative treatment for low-risk E-GISTs, emphasizing the importance of early detection. The limited case numbers may reduce the generalizability of the findings, and further multi-center research involving larger sample sizes is warranted. Although ER is promising, recurrence after R0 resection highlights the need for meticulous patient selection. Future research should focus on refining ER techniques (ESTD, POET, etc.); identifying optimal candidates based on tumor size, location, risk, and genetics; and creating algorithms for treatment selection. Moreover, long-term follow-up is crucial for assessing recurrence and evaluating the potential role of adjuvant therapy following R1 resection in guiding E-GIST management. Future studies should also establish standardized post-ER surveillance protocols, including follow-up intervals (e.g., every 6–12 months), imaging modalities (endoscopy or CT), and recurrence criteria. Comparative analyses of endoscopic and surgical resection and incorporating survival rates, complication rates, quality of life, and cost-effectiveness will provide essential guidance for clinical decision making.