Interpretation of Tumor Response Grade following Preoperative Therapy for Gastric Cancer: An Overview

SIMPLE SUMMARY: The tumor response grade (TRG) of gastric cancer following neoadjuvant therapy is used to quantify therapeutic response. Multiple grading systems exist, with different cut-off values and variable reproducibility. Studies have attempted to associate TRG with survival to assist with prognostication, with inconsistent results, likely secondary to the use of different grading systems between studies and interobserver variability. Radiographic and endoscopic response have also been evaluated as markers of treatment response, but their use in gastric cancer is challenging. This review provides an overview of the current literature regarding the use of TRG in gastric cancer, discussing the interpretation of radiographic and endoscopic response following preoperative treatment, as well as outlining future directions regarding aims to develop, implement, and validate a widely accepted TRG system. ABSTRACT: Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. A pathologic response to preoperative therapies, called the Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, the literature has demonstrated inconsistent results for TRG systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic responses to preoperative therapies using RECIST 1.1 criteria and endoscopically assessed tumor response have demonstrated association with survival; however, their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy, where treatment-related changes can obscure the gastric wall layers. While the response to preoperative therapies with positron emission tomography (PET) has shown promising results in esophageal and esophagogastric junction (EGJ) malignancies, its role in gastric cancer is still under investigation. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview of the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.