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

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.

Keywords: RECIST; gastric cancer; tumor regression score; tumor response grade (TRG).

Figure 1

Representative histologic images of tumor regression grades assigned using schema in CAP Protocol Version 4.1.0.0, (hematoxylin–eosin staining) (a) Rare small groups of carcinoma cells (→) are present within a fibrotic tumor bed in an esophagogastrectomy specimen, corresponding to TRG 1; (b) residual foci of adenocarcinoma (→) persist in a gastrectomy that showed evident treatment effect in the form of ulcer, necrosis, inflammation, and calcifications, consistent with TRG 2; (c,d) extensive residual tumor is readily apparent, with no evidence of tumor regression, corresponding to TRG 3.