Minimally invasive approaches to small gastric stromal tumors: The less with the more

Abstract

In this paper, we comment on the article by Gu et al published in 2024, investigating whether there were differences in the clinical/perioperative outcomes of endoscopic and laparoscopic resections of gastric stromal tumors. Compared with most carcinomas, gastrointestinal stromal tumors are quite common worldwide and have a better prognosis. However, they respond to specific chemotherapies and do not routinely require standard lymphadenectomy. The gastric origin is known to be the most represented. Survival after proven radical surgery is excellent, with recurrences being extremely infrequent. Currently, induction/perioperative chemotherapy for high-risk tumors larger than 5 cm can downstage neoplasia and maintain good survival. Therefore, the standard of care for nonmetastatic, resectable tumors is surgical excision (avoiding formal lymphadenectomy) with or without chemotherapy. In the case of small- (2 cm) to medium- (5 cm) sized tumors, minimally invasive surgical approaches (laparoscopic or robotic) have been advocated, and more recently, a purely endoscopic technique has also been proposed. All these interventions are feasible and effective, although no definitive results have been published to prove the superiority of one over another; however, further investigation of its associated oncologic outcomes is still needed. Unfortunately, rigorous, prospective, randomized controlled trials are challenging to conduct, develop, and receive ethical approval for, whereas the final decision of the surgical route is often related to the availability of instrumentation and local expertise.

Key Words: Gastrointestinal stromal tumor; Gastric stromal tumor; Endoscopic resection; Laparoscopic resection; Robotic resection

Core Tip: Survival after surgery for small, low-risk, gastric stromal tumors is excellent, with few perioperative complications and infrequent recurrences. Minimally invasive surgical approaches, such as laparoscopy, robotics, and endoscopy, should provide optimal clinical outcomes while maintaining oncologic adequacy. Although all of these methods have several strengths and limitations, instrument availability, clinical expertise, and need to preserve oncologic parameters play a crucial role in the choice of one over another.

INTRODUCTION

Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial tumors arising from the gastrointestinal tract, with the gastric location being the most represented. The age-standardized incidence rate of gastric GISTs is 0.93 per 100000 persons, according to a large American database, with a steady increase over the last 20 years[1]. The reason for their increased incidence is related to the optimization of the pathological classification, including the advent of biomolecular and genetic confirmations, while the widespread utilization of radiological imaging (i.e., computed tomography) has also played a role[1]. The overall survival of patients with localized gastric GIST is more than good, ranging from 95% after 5 years, although the application of some oncologic principles of surgery, including the avoidance of ruptures, is mandatory[2-4]. The international guidelines report similar algorithms for the management of gastric GISTs, with surgical excision considered the first choice for resectable, low-risk neoplasms. In this framework, the smallest (< 5 cm), low-risk tumors, without expected sequelae, can be managed by upfront surgery, whereas the largest (> 5 cm), risky tumors should undergo careful multidisciplinary evaluation and be treated within more complex pathways. In these cases, histopathological confirmation with molecular assessment, deeper imaging studies, and perioperative targeted chemotherapy are mandatory[5-7].

Patients who require surgical excision, which is usually achieved without formal prophylactic lymphadenectomy, undergo limited resections with immediate reconstruction, good postoperative outcomes, and scarce impact on physical activity. To optimize these outcomes, some centers are increasing the proportion of gastric GISTs treated by minimally invasive surgery because of the proven efficacy in reducing complications and hospital stays without increasing the rate of tumor rupture[8].

Laparoscopic surgery offers well-known advantages over open surgery in terms of less bleeding, reduced postoperative pain, faster recovery, and shorter hospitalization, and it may be selected for smaller GISTs in favorable anatomical locations, such as the anterior wall of the stomach or the greater curve[9-11]. Since the first comparisons between open surgery and laparoscopy were published, the latter has shown substantial superiority, although few randomized controlled trials (RCTs) are available[12-14]. Interestingly, even the laparoscopic approach to larger gastric GISTs (> 5 cm) seems to be as safe as traditional open surgery[15-17]. Recently, to overcome some of the technical limitations of laparoscopy, in the presence of challenging sites (i.e., smaller curves, or gastric cardia) or larger tumors, the robotic approach has been proposed[18]. The greater dexterity, stable 3-dimensional view and easy application of sutures or picture-in-picture sonography are largely increasing the application of minimally invasive surgery[19,20]. Interestingly, there has been an exponential increase in the use of robotic surgery[2], including in the field of oncological gastric resection[21], although few studies have directly compared the robotic vs laparoscopic approach in RCTs[22-24]. Almost all of them reported some advantages over conventional laparoscopy, such as increased costs and reduced operative times[22-25].

An alternative to (minimally invasive) surgery is endoscopic resection (ER), which includes endoscopic mucosal resection, endoscopic tunneled submucosal resection and endoscopic submucosal dissection[26], with the possibility of effectively treating small (2-5 cm) GISTs located in the esophagus and stomach[9,27,28]. Compared with surgical excision, endoscopic treatment of GISTs offers additional benefits, such as preservation of gastric integrity and function, reduced trauma, less intraoperative bleeding and a lower incidence of complications, even in the presence of larger tumors[29]. Nevertheless, a major concern is the greater difficulty of obtaining R0 resections and the need for surgery in cases of iatrogenic perforation or hemorrhage[27].

To date, no codified selection criteria for the specific applications of surgery, rather than endoscopic treatment, have been published, and the local availability of instruments and expertise drive the final decision[30]. Conversely, the diameter and location of the tumor, together with the performance status, age, and presence of comorbidities, should play the sole pivotal role in the determination of the most suitable surgical approach[31]. Interestingly, some authors have proposed a hybrid approach to combine the advantages of laparoscopic and endoscopic techniques and minimize their risk of complications[32]. All of these issues should also be balanced with the need to preserve oncologic parameters, which is better if data from clinical trials are reviewed. This debate can be resolved using data from a prospective RCT including four arms of study (endoscopic, laparoscopic, robotic and open) with long-term follow-up, although these types of studies would be difficult to conduct due to the large number of patients required and ethical concerns. Therefore, the best available literature reports several retrospective trials, with no more than two arms of comparison or comprehensive reviews[18].

Gu et al[33] reported that both ER and laparoscopy are safe and effective treatments for gastric GISTs. This retrospective study included 206 patients (135 in the ER group and 71 in the laparoscopic group), matched according to the propensity score system, to minimize selection bias, with the covariates being age, sex, tumor size, and tumor location. ER was achieved via endoscopic submucosal dissection, endoscopic full-thickness resection, endoscopic submucosal excavation, or endoscopic tunneled submucosal resection. Laparoscopy includes several different interventions, such as wedge resection, subtotal gastrectomy (including proximal and distal gastrectomy), and total gastrectomy. After the propensity score system, the covariates and baseline characteristics of 59 pairs of patients were balanced. The main findings of this study were that the ER group experienced faster recovery from diet and fewer postoperative symptoms. However, laparoscopy achieved a higher complete resection rate and shorter operative time, with no significant differences in hospital stay, hospital costs, complication rates, pathological features, recurrences, or mortality rates. The results of this study support the idea that patients with smaller gastric GISTs (< 5 cm) benefit from ER, although they should be carefully balanced with risks of incomplete, single-stage, complete resection. Some of the limitations of this study, including the limited experience of endoscopists and the relatively large size of the tumors treated, are clearly highlighted. However, it remains to be proven whether these drawbacks (i.e., incomplete single-stage resections) have real negative predictive power in long-term follow-up. Further similar studies are needed for prospective validation of the ER in clinical practice, especially when dealing with larger tumors.

CLINICAL IMPLICATIONS

Minimally invasive treatment of gastric GISTs has several advantages over open surgery with respect to textbook outcomes and patient recovery. Endoscopy, laparoscopy, and robotic-assisted procedures seem to be feasible and lead to good oncologic outcomes according to preliminary reports, although definitive proof of the superiority of one over another is still lacking.

CONCLUSION

Most fit-for-surgery patients with gastric stromal tumors are candidates for ablative surgery to achieve optimal cancer eradication and the best survival, with the minimum risk of relapses. This decision, together with the choice of the correct timing, should be driven by a dedicated multidisciplinary team with great experience in digestive soft tissue neoplasms. However, in the ongoing era of “precision” medicine, the surgical approach should be personalized, while the local availability of technical resources and expertise is also important. Pure ER, laparoscopy, and robot-assisted procedures are reported to be safe, feasible, and effective, facilitating prompt patient recovery. Endoscopic techniques, whenever possible (depending on lesion location and size), could represent the best option, although more rigorous studies to confirm their efficacy for achieving good oncologic outcomes are needed.