Novel Histologic Categorization Based on Lauren Histotypes Conveys Prognostic Information for Gastroesophageal Junction Cancers—Analysis from a Large Single Center Cohort in Germany

SIMPLE SUMMARY: The incidence of adenocarcinomas of the GE-junction (AEG) increases evermore over the recent decades in the Western world. The postoperative tumor stage with or without multimodal treatment provides important information with regard to post-therapeutic survival. However, this tumor staging may be influenced by the histologic tumor subtype. These subtypes were described by Lauren before and provide substantial prognostic information in gastric cancer patients. The Lauren classification, however, was not yet evaluated in AEG before the purpose of the present retrospective analysis. It was confirmed in a cohort of 1153 AEG patients that Lauren subtypes convey substantial prognostic information after surgical resection. Furthermore, a simplified sub-classification into differentiated and undifferentiated histotypes was developed and evaluated. This newly proposed sub-classification system requires further confirmation by multicentric re-evaluation analyses. ABSTRACT: Adenocarcinoma of the gastroesophageal junction (AEG) ranks among the most common cancers in the Western world with increasing incidence. However, the prognostic influence and applicability of the Lauren classification was not examined in detail before. The purpose of this analysis was to analyze the oncologic outcomes of GE-junction cancer related to the Lauren histotype in a large single center cohort. Data from the prospectively documented database of the Klinikum Rechts der Isar (TUM School of Medicine) for patients undergoing curatively intended oncologic resection for GE-junction cancer between 1984 and 2018 were extracted. Univariate and multivariate regression analyses were performed to identify predictors for overall survival. Kaplan-Meier analyses were done to investigate the survival rates according to the Lauren histotype. After identification of two distinct histologic categories with prognostic implications, propensity score matching (PSM) was performed to balance for confounders and evaluate its oncologic outcomes retrospectively. In the time period indicated, 1710 patients were treated for GE-junction cancer. Exclusion criteria were: R2-resections (n = 134), metastatic disease (n = 296), 30-day mortality (n = 45), Siewert type I (n = 21), and missing/incomplete data (n = 61). Finally, 1153 patients were analyzed. In a multiple variable analysis, age, UICC-stage, all Lauren histotypes, R-stage, and postoperative complications were significant predictors of overall survival. Kaplan Meier analysis demonstrated significant survival differences between intestinal, diffuse, and mixed Lauren-histotypes (p = 0.001 and p = 0.029). Survival rates were comparable between non-classifiable and intestinal Lauren-types (p = 0.16) and between diffuse and mixed types (p = 0.56). When combining non-classifiable, well, and moderately differentiated Lauren-types and combining poorly differentiated intestinal, diffuse, and mixed types, two highly prognostic groups were identified (p < 0.0001). This was confirmed after PSM for possible confounders. The Lauren histotypes demonstrate highly prognostic value after oncologic resection of GE-junction cancer (Siewert type II and type III) in a single center Western patient cohort. A simplified histotype classification based on Lauren subtypes revealed a clear distinction of prognostic groups and should be considered for further evaluation.