Tumor regression grade (TRG) for gastric cancer and radiological methods on predicting response to perioperative chemotherapy. a narrative review

Background and Objective: Perioperative chemotherapy has been increasingly practiced on gastric cancer (GC) in Western Countries where two third of the patients have locally advanced disease at diagnosis. The histological and radiological evaluation of the tumor response to chemotherapy are both cornerstones of this multimodal therapy to predict the oncological outcomes. This article aims to review the current tumor regression grade (TRG) classification systems available and give an overview regarding radiological methods on predicting response to therapy. Methods: A literature search was performed in MEDLINE (PubMed) and Scopus. The terms tumor regression grade, pathologic response, gastric cancer, gastric adenocarcinoma, RECIST 1.1, radiological prediction of response, perioperative, preoperative and neoadjuvant chemotherapy were included. English papers published until December 2021 were reviewed. Key Content and Findings: Several TRG systems (Dworak, Mandard, Ryan, Becker, and Japanese Gastric Cancer Association-TRG) are available in literature, but none has been widely accepted and indicated by the international guidelines for GC. The response evaluation criteria in solid tumors (RECIST) 1.1 are still the most widely used radiological criteria in clinical trials despite their limitations regarding GC. In fact, the stomach is not a solid organ and its lesions are often not measurables. In order to discriminate responders from non-responders patients to perioperative chemotherapy for GC, all imaging techniques have been evaluated in terms of prediction of tumor response to chemotherapy. Indeed, there is still no clear evidence of superiority of one imaging technique over the others. Conclusions: An effective histopathological evaluation method of TRG with an independent prognostic role for GC is urgently needed in clinical practice. A 4-tiered system for grading the regression of the primary tumor, associated with a 3-tiered system for the metastatic lymph nodes achieved a good consensus among experienced pathologists. To date, one of the most promising techniques for prediction of TRG is the diffusion weighted imaging (DWI) magnetic resonance imaging (MRI). As futures perspectives, molecular subgroups analysis and radiomics are spreading widely for the evaluation of their predictive prognostic role.