Independent Stage Classification for Gastroesophageal Junction Adenocarcinoma

SIMPLE SUMMARY: In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. In this study, we investigated 11,340 patients with GEJ adenocarcinoma who received preoperative therapy followed by curative-intent surgery and examined the clinicopathologic factors associated with overall survival (OS). We found that median OS durations in patients with GEJ adenocarcinoma, when sorted by stage, were substantially different from those of patients with adenocarcinoma of the upper or middle esophagus or of the non-cardia stomach. Additionally, preoperative chemoradiotherapy (CXRT) was associated with lower OS rates than chemotherapy after adjustment for the ypT and ypN categories. These results indicate that we should develop an independent GEJ staging system, rather than separating GEJ cancers into either esophageal or gastric cancers and using those staging systems, for better OS prediction. The OS prediction nomogram developed in this study, which included a preoperative therapy regimen, provided reasonable OS prediction. ABSTRACT: In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. Patients with esophageal adenocarcinoma and gastric adenocarcinoma who underwent preoperative therapy followed by surgical resection from 2006 through 2017 were identified in the National Cancer Database. To enable stage-by-stage OS comparisons, tumors were classified into four gross ypTNM groups: ypT1/2, N-negative; ypT1/2, N-positive; ypT3/4, N-negative; and ypT3/4, N-positive. Prognostic factors were examined, and an OS prediction nomogram was developed for patients with abdominal/lower esophageal and gastric cardia adenocarcinoma, representing GEJ cancers. We examined 25,463 patient records. When compared by gross ypTNM group, the abdominal/lower esophageal and gastric cardia adenocarcinoma groups had similar OS rates, differing from those of other esophageal or gastric cancers. Cox regression analysis of patients with GEJ cancers showed that preoperative chemoradiotherapy was associated with shorter OS than preoperative chemotherapy after adjustment for the ypTNM group (hazard ratio 1.31, 95% CI 1.24–1.39, p < 0.001), likely owing to downstaging effects. The nomogram had a concordance index of 0.833 and a time-dependent area under the curve of 0.669. OS prediction in GEJ adenocarcinoma cases should include preoperative therapy regimens. Our OS prediction nomogram provided reasonable OS prediction for patients with GEJ adenocarcinoma, and future validation is needed.