In locally advanced esophageal squamous cell carcinoma patients, neoadjuvant therapy has become a standard therapeutic strategy and been widely administered. Neoadjuvant therapy drastically reduces the metastatic lymph nodes rate as verified in numerous studies including CROSS (Netherlands), JCOG9907/1109 (Japan), NEOCRTEC5010 and CMISG1701 (China) trials, which entails a study to characterize the distribution of lymph node metastasis, and to identify the optimal extent of lymphadenectomy in ESCC patients who received neoadjuvant therapy.~This study aims to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy will improve survival over two-field (thoracic-abdominal) lymphadenectomy for ESCC patients after neoadjuvant therapy.~An estimated 323 patients will be enrolled. Eligible patients will undergo right recurrent laryngeal nerve lymph node dissection (106recR), which will be subjected to intra-operative frozen resection pathological evaluation. If 106recR lymph node reports POSITIVE, patients will undergo esophagectomy with Three-Field lymphadenectomy (n=75). If 106recR lymph node reports NEGATIVE, patients will be randomized at 1:1 ratio into two groups: A) Esophagectomy with Two-Field lymphadenectomy (n=124) or B) Esophagectomy with Three-Field lymphadenectomy (n=124). Analyses will be done according to the intention-to-treat principle.~The primary end point is overall survival (OS), calculated from the date of randomization to the date of death from any cause. Secondary end point is Disease-free survival. Other exploratory end points include tumor recurrence pattern, quality of life, peri-operative complications, and the correlation between metastases of 106recR and cervical lymph nodes.
Comparison of esophagectomy with Two-field Versus Three-field lymphadenectomy in locally advanced ESCC patients after neoadjuvant therapy