Neoadjuvant Chemoradiotherapy versus Chemotherapy for Gastroesophageal Junction Adenocarcinoma; Which Is the Optimal Treatment Option?

SIMPLE SUMMARY: The optimal neoadjuvant treatment modality for locally advanced gastroesophageal junction (GEJ) adenocarcinoma is still debated. Although chemoradiotherapy is set as the standard of treatment for squamous cell cancer, offering high rates of complete clinical and histologic response, the optimal treatment for adenocarcinoma remains a matter of debate. This study retrospectively compared 94 patients with locally advanced adenocarcinoma of the esophago-gastric junction treated with neoadjuvant chemoradiotherapy (n = 27) versus chemotherapy (n = 67) followed by curative surgery. Chemoradiotherapy offered better histological response of the primary tumor, but no benefit in terms of negative resection margins or long-term survival or recurrence. Patients undergoing chemoradiation were shown to have higher rates of cardiovascular complications after surgery. Based on these findings, the added benefit of external beam radiation in the neoadjuvant treatment of locally advanced esophageal adenocarcinoma remains unclear. ABSTRACT: Background: Locally advanced gastroesophageal junction adenocarcinoma (GEJ) is treated with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. The aim of this study was to compare pathologic response and long-term outcomes in junction adenocarcinoma treated with neoadjuvant RCT versus CT. Methods: All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 were retrospectively analyzed. Results: A total of 94 patients were included, 67 (71.2%) RCT and 27 (28.8%) CT. Complete pathologic response was more frequent in RCT patients (13.4% vs. 7.4%, p = 0.009) with a trend to better lymph node control (ypN0) (55.2% vs. 33.3%; p = 0.057). RCT offered no benefit in R0 resection (66.7% vs. 72.1% CT, p = 0.628) and was related to higher postoperative cardiovascular complications (35.8% vs. 11.1%; p = 0.017). Long-term overall and disease-free survival were similar (5-year OS 61.1% RCT vs. 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs. 22.8% CT; p = 0.763). NAT type was neither independently associated with pathologic response nor long-term survival. Discussion: Patients with locally advanced GEJ adenocarcinoma treated with RCT had more postoperative cardiovascular complications but higher rates of complete pathologic response and a trend to superior locoregional lymph node control. This did not translate in a survival or recurrence benefit.