Role of adjuvant chemoradiotherapy after endoscopic treatment of early-stage esophageal cancer: a systematic review

IN TRODUCTION: Esophagectomy combined with lymphadenectomy is currently recommended for patients with high-risk early-stage esophageal cancer after endoscopic treatment (i.e. submucosal tumor invasion [sm2-3], presence of lymphovascular invasion and/or poor tumor differentiation) given the high risk of lymph node metastases. Unfortunately, some patients do not have the physiologic capability to endure surgery. For these patients chemoradiotherapy (CRT) following endoscopic treatment could be an alternative. The aim of this systematic review was to evaluate the evidence on the safety and efficacy of endoscopic treatment combined with CRT in patients with high-risk early-stage esophageal cancer. EVI DEN CE ACQUI SITION: A systematic literature search was performed to identify studies reporting on the safety and efficacy of CRT following endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in patients with esophageal cancer invading the muscularis mucosae or submucosa. Primary outcomes were locoregional recurrence (LRR), disease-free survival (DFS) and overall survival (OS). The secondary outcome was the occurrence of treatment-related adverse events. EVI DEN CE SYNTHE SIS: Six studies were included, comprising a total of 168 patients with early-stage esophageal cancer that underwent endoscopic treatment followed by CRT. Most studies were retrospective case series and included small numbers of patients (11 to 66). All patients had T1a(m3) or T1b(sm1-3) esophageal squamous cell carcinoma. Adjuvant treatment consisted of cisplatin and 5-fluorouracil with concurrent radiotherapy; doses ranging from 40 to 60 Gy. The overall LRR rate ranged between 0-9%. Reported 3-year DFS and OS rates ranged between 69-100% and 87-100%, respectively. In all studies ESD and/or EMR was safely performed without serious complications. The observed CRT treatment-related toxicity (grade ≥3) ranged between 0% and 32%. CONCLUSIONS: This review demonstrates that the current available literature lacks large prospective adequately powered studies and does not allow any firm conclusion regarding the role of endoscopic treatment combined with adjuvant CRT for patients with high-risk early-stage esophageal cancer.