Prognostic Classification of Histopathologic Response to Neoadjuvant Therapy in Esophageal Adenocarcinoma

To evaluate the histopathologic response to neoadjuvant therapy in esophageal adenocarcinoma according to impact on prognosis and to suggest a classification for clinical routine. Measures of histopathologic response to neoadjuvant treatment of esophageal cancer such as Mandard tumor regression grading focus on the effect on the primary tumor. Although lymph node infiltration is of significant prognostic importance, this criterion is mostly not included in the response classifications. A total of 370 patients (89% males, median age: 61 years) with neoadjuvant radiochemotherapy (40 Gy, 5-FU, cisplatin) or chemotherapy (MAGIC or FLOT) for cT3, Nx, M0 esophageal adenocarcinoma were included in the analysis. All patients had undergone transthoracic en bloc esophagectomy, with a median of 27 resected lymph nodes and a R0-resection rate of 92%. Histopathologic regression grading differentiated major or minor response according to less or more than 10% vital cells in the primary tumor. The lymph nodes were classified as ypN0 or ypN+. From the patients with R0 resection and M0 category, 3 groups with significantly different 5-year survival rates (5-YSR) could be differentiated: 1. Major response and ypN0 (n=100) with 5-YSR of 64% 2. Either major response and ypN+ (n=34) 5-YSR 42% or minor response and ypN0 (n=84) 5-YSR 44%, together 42% 5-YSR 3. Minor response and ypN+ (n=111) and 5-YSR of 18%. A combined classification of primary tumor regression and lymph node status in 3 grades represents a simple and reproducible prognostic classification of the effect of neoadjuvant treatment in esophageal adenocarcinoma.