UICC Staging after Neoadjuvant/Perioperative Chemotherapy Reveals No Significant Survival Differences Compared to Primary Surgery for Locally Advanced Gastric Cancer.

Background: The applicability of UICC TNM staging for gastric cancer (GC) patients treated with neoadjuvant chemotherapy (nCTX) and surgery was not yet analyzed in comparison to patients undergoing primary surgery (PS). The purpose of this analysis was to analyze if the prognostic impact of TNM staging after nCTx is comparable with PS. Methods: Data for patients having been treated for GC with or without nCTx between 1990 and 2016 were analyzed. Uni-(URA) and multivariable regression analyses (MRA) were performed to identify predictors. Survival according to the UICC 8th edition stages was analyzed by the Kaplan−Meier method and cox regression analysis. Propensity score matching (PSM) was performed to balance for confounders. Results: 1149 patients with GC were eligible for primary analysis. URA demonstrated age (p < 0.0001), tumor localization (p < 0.0001), clinical UICC-stage, complications, UICC stage 0, IIB-IIIC, Lauren subtype, grading, and R-stage to be significantly associated with OS. MRA revealed that age, distal tumor localization, more than 25 dissected lymph nodes, UICC stage 0, IIB-IIIC, and Lauren subtype were significantly and independently related to OS. After PSM, survival analyses revealed only a significant difference for pN2/ypN2 (p = 0.03), while all other T and N stages were comparable. Conclusion: UICC dependent survival stages do not change significantly after nCTx treatment for GC. Therefore, UICC staging in its present version is applicable to patients undergoing nCTx.

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

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.

Significance of Lauren Classification in Patients Undergoing Neoadjuvant/Perioperative Chemotherapy for Locally Advanced Gastric or Gastroesophageal Junction Cancers-Analysis from a Large Single Center Cohort in Germany.

BACKGROUND: the purpose of this analysis was to analyze the outcomes of multimodal treatment that are related to Lauren histotypes in gastro-esophageal cancer (GEC). METHODS: patients with GEC between 1986 and 2013 were analyzed. Uni- and multivariate regression analysis were performed to identify predictors for overall survival. Lauren histotype stratified overall survival (OS)-rates were analyzed by the Kaplan-Meier method. Further, propensity score matching (PSM) was performed to balance for confounders. RESULTS: 1290 patients were analyzed. After PSM, the median survival was 32 months for patients undergoing primary surgery (PS) and 43 months for patients undergoing neoadjuvant chemotherapy (nCTx) ahead of surgery. For intestinal types, median survival time was 34 months (PS) vs. 52 months (nCTx+surgery) p = 0.07, 36 months (PS) vs. (31) months (nCTx+surgery) in diffuse types (p = 0.44) and 31 months (PS) vs. 62 months (nCTx+surgery) for mixed types (p = 0.28). Five-/Ten-year survival rates for intestinal, diffuse, and mixed types were 44/29%, 36/17%, and 43/33%, respectively. After PSM, Kaplan-Meier showed a survival benefit for patients undergoing nCTx+surgery in intestinal and mixed types. CONCLUSION: the Lauren histotype might be predictive for survival outcome in GEC-patients after neoadjuvant/perioperative chemotherapy.

Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype.

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15-140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24-3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.

Clinical impact of molecular classifications in gastric cancer.

Treatment options to gastric cancer (GC) have been changing in recent years from a standard to a tailored approach. Different individualized procedures can range from endoscopic resection, D2 with open or minimally invasive approach, to neo-adjuvant therapy followed by extended surgery. In more advanced stages, a combined approach with the inclusion of intraperitoneal chemo-hyperthermia (HIPEC) may represent a new advanced option. The inclusion of histological type according to Laurén classification in the flowchart of treatment could increase both accuracy and effectiveness of such tailored approach. New molecular classifications of GC have been introduced recently and translational clinical studies are ongoing. These classifications are expected to be included in multidisciplinary treatment of GC. In particular, in the group with microsatellite instability a less extended lymphadenectomy may be proposed. Also tailored neo-adjuvant treatment may be proposed according to molecular classifications. The group of patients with epithelial-to-mesenchymal transition shows very high propensity to peritoneal dissemination, as well as N-metastases, and may benefit from prophylactic HIPEC and extended lymphadenectomy when confirmed in prospective trials.