Endoscopic submucosal dissection for early gastric cancer: A review of comparative perspectives on treatment outcomes vs gastrectomy

Abstract

Endoscopic submucosal dissection is a key technique for the minimally invasive treatment of early-stage gastric cancer. Offering the advantages of minimal trauma, high safety and the ability to resect tumours intact, it has been incorporated into standard treatment protocols in many countries. This article systematically reviews the clinical value, recent developments and controversies surrounding endoscopic submucosal dissection, drawing on relevant research and clinical guidelines. It compares its efficacy with that of surgical procedures, clarifies the criteria for indications, analyses the bottlenecks in its application and proposes future research directions, thereby providing a reference for its standardised clinical application.

Key Words: Early gastric cancer; Endoscopic submucosal dissection; Gastrectomy; Minimally invasive treatment; Review

Core Tip: Drawing on a retrospective cohort study of 206 cases, as well as relevant guidelines and controlled trials, this article provides a systematic review of the application of endoscopic submucosal dissection in the treatment of early-stage gastric cancer. It highlights the procedure’s minimally invasive and safe advantages, as well as its status as a standard treatment in multiple countries. Furthermore, the article summarises recent developments, ongoing debates, comparative efficacy data and indications, whilst proposing future research directions, identifying application bottlenecks and offering recommendations for wider adoption.

INTRODUCTION

Stomach cancer is one of the most common types of cancer worldwide. In 2022, there were 968350 new cases of stomach cancer worldwide, with 659853 deaths[1,2]. Helicobacter pylori infection is the primary risk factor, with Asia and Eastern Europe being high-prevalence regions[3]. Endoscopic resection encompasses widely practised techniques such as endoscopic mucosal resection and endoscopic submucosal dissection (ESD), with ESD being the treatment method most strongly recommended in current guidelines for early gastric cancer (EGC)[4]. ESD is a minimally invasive treatment for early-stage gastric cancer. ESD enables the en bloc, intact resection of early-stage gastric tumours, facilitating accurate pathological assessment[5-7]. Compared with patients undergoing open surgery, those undergoing ESD undoubtedly experience less surgical trauma and enjoy an improved quality of life[8,9]. The value of ESD is further enhanced when endoscopy can easily detect early-stage gastrointestinal cancer[10,11]. ESD has become a well-established treatment option for early-stage gastric cancer and precancerous lesions, offering good efficacy and a favourable safety profile[12]. It has been incorporated into standard treatment protocols in Japan, South Korea, the United States and other regions, ushering in an era of organ-preserving treatment and rapid recovery for gastric cancer[13,14]. However, there is currently insufficient evidence from direct comparisons between ESD and conventional gastrectomy, and its clinical adoption is hampered by limited understanding. This review is based on a retrospective cohort study of 206 cases conducted by Ling et al[15] at the Affiliated Hospital of North China Medical University in Sichuan, and combines this with controlled studies and clinical guidelines in the field to systematically evaluate the clinical utility, quality of evidence, indications, and potential for wider adoption of ESD.

ADVANCES IN THE FIELD AND KEY CONTROVERSIES

Recent advances in the field

Technological innovations: A range of modified techniques for conventional ESD have become widely adopted, including the pocket-forming method, the tunnel method, the traction-assisted method and the saline-infused therapeutic endoscopy method[16-18].

Local haemostasis: Purastat, TC-325 haemostatic powder and Nexpowder have demonstrated high haemostatic efficacy in acute gastrointestinal bleeding[19-21]. Artificial intelligence and machine learning models were used to predict delayed bleeding; there was a significant difference in area under the receiver operating characteristics curve between the BEST-J score and the newly developed predictive model (area under the receiver operating characteristics curve difference = 0.125, P = 0.012). The new predictive model is better able to assess the risk of bleeding following ESD in Chinese patients with EGC, outperforming the BEST-J score[22].

Key controversies in the field

Controversy regarding long-term efficacy: Whilst the short-term benefits of ESD are clear, there is a lack of high-quality comparative evidence regarding long-term recurrence rates and survival rates compared with conventional gastrectomy[23,24].

Disputes regarding the scope of indications; strict indications limit its use; relaxing these indications may increase the risk of residual disease or recurrence[25,26]. Controversy surrounding the widespread adoption of the technology, a steep learning curve, high demands on equipment and staff, and poor accessibility at the grassroots level[27-29]. Evaluation of endpoint controversies: Whether mucosal barrier biomarkers can replace hard oncological endpoints such as recurrence, metastasis, and survival[30,31]. There is controversy regarding the level of evidence; the majority of studies are retrospective in design, with significant selection bias, limiting the generalisability of their conclusions.

THE AUTHOR’S MAIN ARGUMENT

Equivalent short-term efficacy, with superior safety

A retrospective study by Ling et al[15] showed that there was no statistically significant difference in the overall treatment efficacy between ESD and conventional gastrectomy (92.86%, χ² = 2.293, P > 0.05); The complication rate for ESD was only 5.56%, significantly lower than the 13.27% for conventional surgery; there was also less intraoperative blood loss, shorter operative time and faster recovery of oral intake (2.43 days), demonstrating clear benefits of the minimally invasive approach (Table 1)[15].

Table 1 Comparison of key perioperative indicators between endoscopic submucosal dissection and conventional gastrectomy.

Key performance indicators	ESD group	Conventional gastrectomy group	Statistical results	Conclusion
Overall treatment success rate	92.86%	Slightly lower	χ² = 2.293, P > 0.05	There was no statistically significant difference between the two groups
Incidence of complications	5.56%	13.27%	P < 0.05	The ESD group offers superior safety
Intraoperative blood loss	Less	More	-	The ESD group is superior
Duration of the operation	Shorter	Longer	-	The ESD group is superior
Recovery time after oral administration	2.43 days	Longer	-	The ESD group is superior

ESD: Endoscopic submucosal dissection.

Strict adherence to the criteria for curative resection

According to the “Japanese Guidelines for the Treatment of Gastric Cancer 2021”, curative resection by ESD must meet the following criteria: Tumour depth of invasion ≤ T1a, moderately to well-differentiated, no ulceration, no lymphovascular invasion, and negative surgical margins (R0 resection). Cases where resection is not curative should be promptly assessed for additional surgery or adjuvant therapy[32].

Protection of the mucosal barrier as an additional benefit

Following ESD, there was a more significant improvement in markers of intestinal barrier damage, such as diamine oxidase and endotoxins, suggesting that minimally invasive surgery causes less disruption to gastrointestinal physiology. However, biomarkers cannot replace core oncological endpoints such as recurrence, metastasis and survival rates; they can only serve as supplementary assessment indicators[15].

The evidence has clear limitations

The core study was a single-centre retrospective cohort study, which suffered from selection bias, baseline imbalance and a lack of long-term follow-up data. It was therefore unable to establish that ESD is definitively superior to conventional gastrectomy, and the generalisability of its conclusions is limited (Table 2).

Table 2 Assessment of the quality and limitations of the research evidence.

Evaluation criteria	Features	Level of evidence
Research design	Single-centre retrospective cohort	Below average
Sample size	206 cases of early-stage gastric cancer	Intermediate
Follow-up interval	Short-term perioperative period; no long-term survival	The evidence is incomplete
Bias risk	Selection bias, baseline imbalance	Limited generalisability
Strength of the conclusion	Short-term benefits are certain, but long-term efficacy is uncertain	This requires validation through prospective studies

COMPARISON OF ESD AND SURGICAL OUTCOMES

Short-term efficacy

Retrospective studies conducted by Ling et al[15] and Hahn et al[33] both indicate that, in the treatment of early-stage gastric cancer, the ESD group achieved better short-term therapeutic outcomes than the conventional surgical group. While both studies found no statistically significant difference in the overall treatment response rates between the two groups, the study by Hahn et al[33] reported that the ESD group performed better in terms of safety indicators, such as the incidence of acute complications and surgery-related mortality.

Long-term outcomes

The Japanese Clinical Oncology Group 0607 and Japanese Clinical Oncology Group 1009/1010 multicentre prospective studies demonstrated that the 5-year overall survival rate for ESD is comparable to that of surgical gastrectomy[34]. Retrospective propensity score matching studies by Fukunaga et al[35] and Lim et al[36] indicated that the 5-year surgical outcomes for surgical resection (SR) were superior to those of ESD and that SR had a broader range of indications. A meta-analysis of data by Xu et al[37] evaluating long-term outcomes also showed no significant advantage for SR treatment; however, the 5-year disease-free survival rate for SR patients was superior to that of patients receiving ESD under extended indications. The poor prognosis associated with ESD is primarily linked to synchronous or metachronous gastric cancer remaining in the residual stomach post-procedure; whether ESD is a reasonable treatment option for patients meeting the absolute indications for EGC in such cases requires further investigation[37-41]. Endoscopic surveillance is required post-ESD to detect synchronous or metachronous lesions. A multicentre retrospective cohort study by Kato et al[42] demonstrated that the incidence of metachronous cancer following ESD remains stable, and that standardised endoscopic surveillance allows for the endoscopic resection of almost all recurrent lesions. Takizawa et al[34] also confirmed that ESD-related complications are clinically manageable; among 275 patients histologically diagnosed with UD-EGC and without radiological evidence of metastasis, the 5-year overall survival rate reached 99.3% (95%CI: 97.1%-99.8%)[43]. In summary, ESD for EGC offers the advantages of minimally invasive surgery and favourable long-term survival outcomes. Although some studies indicate that its recurrence and disease-free survival rates are slightly inferior to those of SR, its safety and efficacy have been confirmed by numerous studies. Standardised post-operative endoscopic surveillance is key to improving prognosis and managing synchronous or metachronous lesions (Table 3)[15,33-37,42].

Table 3 Summary table of clinical studies on endoscopic submucosal dissection for early-stage gastric cancer.

Research level	Type of research	Key findings	Ref.
Short-term efficacy and safety	Retrospective study	The short-term efficacy of the ESD group was comparable to that of the conventional surgery group, with no statistically significant difference in the overall response rate	Ling et al[15]
	Retrospective study	The ESD group demonstrated superior safety in terms of short-term efficacy	Hahn et al[33]
Long-term outcome	Multicentre prospective study	The 5-year OS rate for ESD is comparable to that of surgical gastrectomy	Takizawa et al[34]
	Propensity score matching retrospective study	The five-year recurrence-free survival rate for SR is superior to that of ESD, and it has a broader range of indications	Fukunaga et al[35], Lim et al[36]
	Integration of research data	SR shows no clear advantage, but patients with SR have a better 5-year disease-free survival than those with ESD in the expanded indication	Xu et al[37]
Prognosis and monitoring	Multicentre retrospective cohort study	The incidence of post-ESD synchronous cancer remains stable, and standardised monitoring allows for the management of almost all recurrent lesions	Kato et al[42]
	Related research	Complications associated with ESD are manageable, with a 5-year OS rate of 99.3% in specific patients (95%CI: 97.1%-99.8%)	Takizawa et al[34]
Summary		ESD is a minimally invasive, safe and effective treatment for early-stage gastric cancer, although some outcomes are inferior to those of surgical resection; synchronous or metachronous gastric cancer following the procedure affects prognosis and requires standardised endoscopic monitoring

ESD: Endoscopic submucosal dissection; OS: Overall survival; SR: Surgical resection.

INDICATIONS FOR ESD

The indications for ESD have moved beyond the classic absolute criteria to encompass larger, well-differentiated lesions, as summarised by Lee et al[23] in his review of the guidelines issued by the Korean Gastric Cancer Association (2024), the Japanese Society of Gastrointestinal Endoscopy (2021) and the European Society of Gastrointestinal Endoscopy (particularly regarding precancerous lesions and lesion management) (MAPS III 2025) (Table 4)[32,44-46].

Table 4 Comparison table of regional guidelines on indications for endoscopic submucosal dissection in early-stage gastric cancer by subtype (Korean Gastric Cancer Association/Japanese Society of Gastrointestinal Endoscopy/MAPS III).

Tumour classification and characteristics	South Korea (Korean Gastric Cancer Association 2024)	Japan (Japanese Society of Gastrointestinal Endoscopy 2021)	Europe (MAPS III 2025)
Differentiated intraepithelial carcinoma	-	-	-
No ulceration; diameter ≤ 2 cm	Standard indications	Absolute indications	Recommended for use
No ulceration, diameter > 2 cm	Provided that the criteria for curative resection are met	Absolute indications	Recommended for use
Accompanied by ulcer formation, diameter ≤ 3 cm	Provided that the criteria for curative resection are met	Absolute indications	Recommended for use
Associated with ulcer formation, diameter > 3 cm	Endoscopic submucosal dissection resection is not recommended	Relative indications	Not recommended
Undifferentiated intraepithelial carcinoma	-	-	-
No ulceration; diameter ≤ 2 cm	This should be chosen with due care following careful consideration	Absolute indications	This could be considered for implementation
Submucosal invasive carcinoma (SM1, depth of invasion ≤ 500 μm)	-	-	-
Differentiated, longest diameter ≤ 3 cm	Following pathological assessment, the patient is deemed eligible for curative resection	Relative indications	This could be considered for implementation

FUTURE RESEARCH DIRECTIONS

Conduct high-level evidence-based research: Carry out multicentre, large-sample, prospective randomised controlled trials to provide data on recurrence rates and survival rates over a period of five years or more, thereby establishing the long-term oncological value of ESD.

Develop a precise system for stratifying indications: Establish individualised eligibility criteria by combining tumour differentiation, depth of invasion, molecular subtyping and ctDNA minimal residual disease[47-49]. Promote standardisation of techniques and training: (1) Optimise instruments; (2) Streamline procedures; and (3) Establish a unified quality control system[3,50]. Clarify the association between biomarkers and prognosis: Elucidate the relationship between the mucosal barrier, tumour markers and long-term prognosis[51,52].

Explore new models of combination therapy: Investigate the application of ESD in combination with targeted therapy, immunotherapy, novel mucosal injectables and endoscopic sealing techniques in high-risk early-stage gastric cancer[53-56].

CONCLUSION

ESD is a landmark technique for the minimally invasive treatment of early-stage gastric cancer. It offers proven short-term efficacy, superior safety and outstanding organ preservation, whilst achieving curative outcomes comparable to those of conventional gastrectomy. The current key challenges in this field include a lack of high-quality long-term evidence, uneven dissemination of the technique, and the need to refine the precision of its indications. Clinicians should strictly adhere to guidelines and ensure that ESD is performed in a standardised manner at experienced centres[57]. Moving forward, a focus on prospective studies, precise patient stratification and standardisation of techniques will further promote the standardised adoption of ESD, reduce mortality from early-stage gastric cancer and improve long-term patient outcomes[58]. The eCura scoring system may provide valuable insights for future research into patient management strategies and corresponding follow-up outcomes[59,60]. Ultimately, these innovations are expected to further optimise treatment strategies for early-stage gastric tumours, improve patient prognosis and make early-stage gastric cancer a more manageable and treatable disease[61].