Endoscopic submucosal dissection for early gastric cancer: A major challenge for the west

Abstract

Gastric cancer (GC) is the 5^th most common cancer and the 3^rd most common cause of cancer mortality worldwide. Two main endoscopic resective techniques exist for early GC (EGC): Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). ESD has been widely embraced in the last decade because it allows radical en bloc resections and is associated with better outcomes, as compared to EMR. However, the lack of training opportunities and flat learning curve due to low volume of EGC cases represent major obstacles to obtain proficiency on ESD in the West. As this procedure is highly efficient for the treatment of EGC, dedicated training programs with a stepwise approach and updated guidelines for ESD embracement are needed in Western countries.

Core Tip: Endoscopic submucosal dissection (ESD) is a highly efficient treatment modality for early gastric cancer. However, the adoption of ESD in Western countries poses two main challenges: Low prevalence of early gastric cancer and lack of expertise in such advanced endoscopic technique. Dedicated training programs are needed to safely embrace ESD in Western countries.

INTRODUCTION

Gastric cancer (GC) is the 5^th most common cancer and the 3^rd most common cause of cancer mortality worldwide[1]. However, Eastern countries such as China, Korea or Japan have significantly higher incidence of the disease, and GC represents one of the leading causes of cancer-related mortality[2]. Although systemic therapies with chemotherapy and immunotherapy have evolved overtime, resective treatment (endoscopically or surgically) remains the cornerstone of curative treatment[3].

Gastrectomy for cancer is a procedure associated with relatively high morbidity, especially in low volume centers[4]. For instance, in two previous European randomized trials mortality rates after D2 gastrectomy reached up to 10.0% and 13.0%[5,6]. A recent study analyzed 67389 patients undergoing oncologic gastric resection in Germany between 2008 and 2018; 5.2% of patients had anastomotic leakage and mortality occurred in 6.7% of cases after total gastrectomy[7]. An Asian trial conducted by experienced surgeons in 24 specialized centers with high volume of cases also showed high morbidity after D2 gastrectomy (overall incidence of surgery-related complications was 20.9%)[8]. Therefore, adopting less invasive resective therapies avoiding a major surgery should be prioritized whenever possible.

Early GC (EGC) includes tumors confined to the mucosa (T1a) or submucosa (T1b). Intramucosal tumors with a size less than 2 cm, well differentiated, without ulceration, and without lymphovascular invasion have very low risk of lymph node metastasis (1%-5%). For this reason, current guidelines recommend endoscopic resection as first line treatment for early tumors meeting these criteria[9,10]. Two main endoscopic resective techniques exist: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is a relatively simple procedure which is widely adopted and allows for both pathologic diagnosis and treatment by complete resection. ESD has been embraced in the last decade as one of the main therapies for EGC because it allows dissection of the entire lesion along with radical en bloc resections. However, this technique is considered technically more difficult and is potentially associated with higher complication rates.

ESD: CHALLENGES FOR THE WEST

A recent study has compared efficacy and safety between EMR (n = 39) and ESD (n = 39) for the treatment of EGC and precancerous lesions in elderly patients (> 65 years old). The curative resection rates (74% vs 51%) and en bloc resection rates (97% vs 71%) were significantly higher with ESD (P = 0.001). Intraoperative bleeding was higher and operative time longer with ESD, as compared to EMR. Oncological outcomes (1-year postoperative recurrence rates and 3-year survival rates) were significantly better after ESD[11]. Other studies have also shown the superiority of ESD over EMR for EGC[12-14]. For instance, a previous meta-analysis comprising 10 studies with 4328 Lesions (1916 ESD and 2412 EMR) confirmed that en bloc [odds ratio (OR): 9.69] and histological complete (OR: 5.66) resection rates were significantly higher after ESD, as compared to EMR[14].

Based on the current evidence, ESD should be the selected endoscopic procedure for resection of EGC. However, the adoption of ESD in Western countries poses two main challenges: Low prevalence of EGC and lack of training/expertise in such advanced endoscopic techniques. Current population-based screening guidelines in Japan recommend biennial GC screening via upper gastrointestinal series or upper endoscopy for individuals older than 50 years old[15]. Nationwide organized GC screening programs in South Korea have shown to significantly reduce mortality of the disease on the population[16]. Screening policies increment the detection of early-stage tumors, increase public awareness, and strengthen infrastructure and workforce. Despite such effective screening and surveillance measures, GC screening programs have been implemented in few countries and the disease remains burdened with poor prognosis, particularly in Western countries[17]. Unfortunately, the high number needed to screen and the low expected mortality rate reduction in most Western countries still challenge the execution of population-based endoscopic screening programs for GC[18].

The low number of patients with EGC in most Occidental countries ultimately precludes the appropriate training and expertise on ESD. A previous study evaluated the learning curve for ESD performed by a single operator at a high-volume referral center in the United States. Proficiency benchmarks included > 90% en bloc resection, > 80% histologic negative margins and resection speed > 9 cm² /h. The authors found that proficiency was obtained after approximately 250 cases and concluded that ESD requires significantly more time to learn in the West than in Asia[19]. Another multicenter study in Germany also found that the learning curve for ESD required a high number of cases (proficiency level with around 120 procedures)[20]. A survey-based study inquired 58 endoscopists on how ESD for gastrointestinal lesions was implemented in Western countries; 30 (52%) and 45 (78%) performed ESD in the esophagus and stomach, respectively. Interestingly, the median total number of lesions ever treated per endoscopist in one year was very low: 7 and 6 in the esophagus and stomach, respectively[21]. A French study analyzing data from 16 centers with expert endoscopists also showed that R0 resection and complication rates after ESD did not match those reported by Asian studies, suggesting that further improvement by extended practice was needed[22]. Therefore, it is clear that implementation of effective and safe ESD programs remain a major challenge in Occident.

Overall, ESD is a less invasive alternative to surgery for the treatment of EGC. However, a deficient ESD poses higher risks of procedure-related complications, as well as higher risk of incomplete oncologic resections. This complex endoscopic procedure requires systematic training under the mentorship of expert endoscopists. The lack of training opportunities and flat learning curve due to low volume of cases represent major obstacles to obtain proficiency in the West. Therefore, an ESD formal training program should be encouraged for Western endoscopists.

An Italian center described their training strategy for adopting skills before performing ESD. The learning process included: visiting a high-volume center in Tokyo for 3 months observing at least 3-5 complete procedures per day, initial practice on isolated pig stomachs, and finally performing ESD in 3 patients with EGC under direct and strict supervision of the expert[23]. The European Society of Gastrointestinal Endoscopy guidelines also propose an ESD training algorithm for Western endoscopists which includes: Knowledge acquisition of techniques, instrumentation and electrosurgical endoscopic equipment by self-study, practice on animal models (explanted organs and live animal models), observing experts performing ESD (4-5 wk) in referral centers, hands-on workshops with expert guidance, and starting with ESD in humans on very selected cases (e.g., small lesion in the lower part of the stomach)[24]. Novel gastric ESD non-animal training models have been recently described that appear to significantly improve skills of inexperienced ESD trainees[25]. Finally, the development of flexible robotic systems for ESD will potentially help reducing the technical challenges of ESD and shortening the learning curve of inexperienced endoscopists[26].

CONCLUSION

ESD is a complex endoscopic procedure that requires extensive training and considerable endoscopic skills. As this procedure is highly efficient for the treatment of EGC, dedicated training programs with a stepwise approach and updated guidelines for ESD embracement are needed in Western countries.