Kohei Takizawa1,2, Hiroyuki Ono3, Noriaki Hasuike4, Atsuo Takashima5, Keiko Minashi6, Narikazu Boku7, Ryoji Kushima8, Hiroshi Katayama5, Gakuto Ogawa5, Haruhiko Fukuda5, Junko Fujisaki9, Ichiro Oda10, Tomonori Yano11, Shinichiro Hori12, Hisashi Doyama13, Kingo Hirasawa14, Yoshinobu Yamamoto15, Ryu Ishihara16, Satoshi Tanabe17, Yasumasa Niwa18, Masahiro Nakagawa19, Masanori Terashima20, Manabu Muto21. 1. Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumicho, Suntougun, Shizuoka, 411-8777, Japan. k.takizawa@scchr.jp. 2. Department of Surgery, School of Medicine, Keio University, Minato City, Japan. k.takizawa@scchr.jp. 3. Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumicho, Suntougun, Shizuoka, 411-8777, Japan. 4. Hasuike Clinic, Kobe, Japan. 5. Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan. 6. Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan. 7. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 8. Department of Pathology, Shiga University of Medical Science, Otsu, Japan. 9. Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 10. Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan. 11. Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan. 12. Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 13. Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan. 14. Division of Endoscopy, Yokohama City University Medical Center, Yokohama, Japan. 15. Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Japan. 16. Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan. 17. Department of Advanced Medicine Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan. 18. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan. 19. Department of Endoscopy, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan. 20. Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan. 21. Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Abstract
BACKGROUND: While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. METHODS: The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. RESULTS: Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1-99.8). CONCLUSIONS: ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.
BACKGROUND: While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. METHODS: The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. RESULTS: Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1-99.8). CONCLUSIONS: ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.