Diffuse-Type Histology Is Prognostic for All Siewert Types of Gastroesophageal Adenocarcinoma

Abstract

Purpose: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type.

Materials and methods: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications.

Results: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months.

Conclusions: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

Keywords: Esophageal cancer; Esophagogastric junction adenocarcinoma; Gastric cancer; Histology evaluation; Siewert-Stein classification.

Fig. 1. CONSORT diagram of the study cohort. Classification of patients with locally advanced GEJA who underwent curative intent surgical resection.

GEJA = gastroesophageal junction adenocarcinoma.

Fig. 2. Kaplan-Meier survival curves. Curves for OS (A), with and without positive pathologic LNs (B), and treatment response by tumor regression grade (C) diffuse- vs. intestinal-type histology.

OS = overall survival; LN = lymph node; HR = hazard ratio.

Fig. 3. Flowchart depicting the elements required for a comprehensive GEJA work-up including: 1) EGD/EUS for anatomic localization (Siewert classification and extent of proximal esophageal and distal gastric involvement), evaluation of tumor depth and regional LNs for TNM staging, and pretreatment biopsies; 2) evaluation of preoperative biopsies for Lauren histologic type, PD-L1 (CPS), MSI, and HER2 overexpression status; 3) CT scan ± PET scan of the chest, abdomen, and pelvis for evaluation of regional LN basins and metastatic disease for TMN staging, tumor invasion into adjacent organs, and gastric wall thickening indicating possible involvement; 4) evaluation by a multidisciplinary team; and 5) assessment of patient fitness and nutritional status for pretreatment optimization and determination of treatment candidacy.

GEJA = gastroesophageal junction adenocarcinoma; EGD = esophagogastroduodenoscopy; EUS = endoscopic ultrasonography; LN = lymph node; TNM = tumor, node, metastasis; PD-L1 = programmed cell death ligand 1; CPS = combined positive score; MSI = microsatellite instable; HER2 = human epidermal growth factor receptor 2; CT = computed tomography; PET = positron emission tomography; GEJ = gastroesophageal junction.