Waku Hatta, MD, PhD and Takuji Gotoda, MD, PhD, FASGE, FACG, FRCP
Endoscopic resection is divided into endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR has been widely accepted as an effective, minimally invasive treatment for early gastric cancer (EGC), categorized as a T1a or T1b gastric cancer,1 with a negligible risk of lymph node metastasis (LNM). ESD is an alternate endoscopic technique that allows en bloc resection of lesions irrespective of size, thereby permitting precise histopathological assessment of the resected specimen. ESD has largely replaced EMR for the treatment of EGC in many Eastern countries. Indeed, in Japan, ESD was carried out in 93.1% (3673/3946) of EGC cases treated endoscopically as of June 2016.2 Given its potential advantages over EMR, this procedure has begun to gained traction in some Western countries as well.3
When ESD or EMR is selected for patients with EGC, it is necessary to evaluate its curability. In addition, when follow-up with no additional treatment is selected after ESD or EMR, it is important to know the risk for recurrence and that of secondary gastric cancer in such patients.
Since the incidence of gastric cancer is higher in Eastern countries, the majority of outcome data about ESD and EMR for EGC, including the absolute and expanded indications for endoscopic resection in the current Japanese Guidelines (Japan Gastric Cancer Association [JGCA] and Japan Gastroenterological Endoscopy Society), are based on data derived from Eastern cohort studies.4,5 More recently, based on the favorable results of a recent multicenter confirmatory trial in Japan,6 expanded indications in the differentiated-type EGC (differentiated, intramucosal cancer measuring ≥ 2 cm in diameter and without ulceration [scar] [UL], and differentiated, mucosal cancer measuring < 3 cm with UL) will become an absolute indication for ESD in the next version of JGCA guidelines. Furthermore, additional outcomes data on EGC are beginning to be compiled from Western countries. In this chapter, we will review ESD and EMR outcomes and surveillance after treatment of EGC.
Assessment of Curability After Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection
For assessing the curability after ESD or EMR, tumor size, invasion depth, histopathological type, lymphatic invasion, venous invasion, UL, horizontal margin (HM) and vertical margin (VM) need to be evaluated. According to the Japanese Classification of Gastric Carcinoma, 3rd English edition,1 the depth of submucosal invasion is subclassified into SM1 (tumor invasion into the submucosa < 500 µm from the muscularis mucosa) and SM2 (tumor invasion into the submucosa ≥ 500 µm from the muscularis mucosa). Histopathological subtypes are classified as differentiated or undifferentiated, the latter of which includes poorly differentiated adenocarcinoma and signet-ring cell carcinoma.1
According to the current Japanese Guidelines, the curability after ESD or EMR for EGC is classified into 3 groups: curative resection, curative resection for expanded indication, and noncurative resection4,5 (Figure 28-1). En bloc resection with no lymphovascular invasion and negative resection margins are required for curative resection or that for expanded indication.
Clinical Outcome of Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection
There are no randomized, controlled trials comparing ESD to EMR for the treatment of EGC. However, numerous retrospective studies, whose data were grouped in 3 meta-analyses, have compared the 2 techniques.7-9 According to these meta-analyses, when compared to EMR, ESD achieved a higher en bloc resection rate (92% vs 52%), complete (R0) resection (negative HMs and VMs) rate (82% to 92% vs 42% to 43%), and lower local recurrence rate (0.6% to 0.8% vs 5.0% to 6.4%), irrespective of the size of the tumor7–9 (Table 28-1). Although the current European Society for Medical Oncology (ESMO)10 Guidelines propose that EMR is acceptable for lesions smaller than 10 to 15 mm, data show that ESD is superior to EMR in terms of en bloc and complete resection rates even for smaller lesions (< 10 mm).
The main disadvantages of ESD over EMR include a lengthier procedure and higher risk for serious adverse events. Based on these meta-analyses, ESD was associated with a longer procedure time (59.4 minutes more when compared to EMR) and higher perforation rate (4.3% to 4.5% vs 0.9% to 1.0%)7,8 (see Table 28-1). There was no ESD- or EMR-related mortality reported, and all-cause mortality did not differ between the 2 techniques (0.9% vs 0.9%).7
Curative resection can be achieved for differentiated, intramucosal cancer measuring < 2 cm in diameter without UL, lymphovascular invasion, and when negative HM and VM are attained (see Figure 28-1). The risk of LNM in this group is virtually zero. In fact, a collaborative study from Japan showed that none (0/6456) of the patients with such lesions had metastatic recurrence after ESD.11 Based on these data and according to the current Japanese Guidelines,4,5 no additional treatment is needed after curative resection (Figure 28-2). Criteria for curative resection are expected to be updated based on new available data. For example, some of the expanded curative criteria will become “curative resection” in the next version of JGCA guidelines, as shown in the “curative resection for tumors of expanded indication” section (see Figure 28-1).
Similar to the Japanese Guidelines,4,5 the European (European Society of Gastrointestinal Endoscopy [ESGE], ESMO) guidelines3,10 do not recommend any additional treatment following curative resection. In the United States, the National Comprehensive Cancer Network Clinical Guidelines12 (NCCN guidelines) also regard EMR and ESD as potential therapeutic options for Tis or T1a cancers ≤ 2 cm.
Surveillance After Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection
After ESD or EMR for EGC, careful follow-up is necessary for surveillance for secondary gastric cancers. The 5-year and 10-year cumulative incidences of secondary gastric cancer have been estimated to be around 9.5% and 22.7%, respectively.13 Furthermore, a multicenter retrospective study revealed that 19% of synchronous gastric cancers were not detected until the initial ESD, and that almost all of these secondary lesions were treatable by ESD during scheduled endoscopic surveillance (6 to 12 months).14 The current Japanese Guidelines recommend endoscopic surveillance at intervals of 6 to 12 months,4,5 whereas ESGE and NCCN guidelines recommend annual endoscopy from 1 year after ESD or EMR.3,12 In summary, the following endoscopic surveillance is recommended after curative ESD or EMR of EGC (Figure 28-3):
- Intensive (every 6 months) surveillance is preferred in the first year after ESD or EMR to detect missed concomitant gastric cancers.
- Endoscopic surveillance at intervals of (6 to) 12 months should be performed for at least 10 years after ESD or EMR.
Curative Resection for Tumors of Expanded Indication
In Eastern countries, endoscopic treatment criteria are based on the Japanese Guidelines as previously shown.4,5 Curative resection for expanded indication is defined by the following findings (see Figure 28-1):
- Differentiated, intramucosal cancer measuring ≥ 2 cm in diameter without UL.
- Differentiated, mucosal cancer measuring < 3 cm with UL.
- Undifferentiated, mucosal cancer measuring < 2 cm without UL.
- Differentiated cancer measuring < 3 cm with a submucosal invasion depth of < 500 µm and without UL.