Perioperative Tailored Treatments for Gastric Cancer: Times Are Changing

Abstract

Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. Unfortunately, nearly half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery). In this review, we summarize the evidence of potential tailored approaches in perioperative treatment of G/GEJ cancer, with a special focus on patients with human epidermal growth factor receptor-2(HER2)-positive and microsatellite instability-high (MSI-H) tumors. In patients with resectable MSI-H G/GEJ adenocarcinoma, the ongoing INFINITY trial introduces the concept of non-operative management for patients with complete clinical-pathological-molecular response, and this could be a novel and potential practice changing strategy. Other pathways involving vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), claudin18 isoform 2 (CLDN18.2), and DNA damage repair proteins are also described, with limited evidence until now. Although tailored therapy appears to be a promising strategy for resectable G/GEJ cancer, there are several methodological issues to address: inadequate sample size for pivotal trials, underestimation of subgroup effects, and choice of primary endpoint (tumor-centered vs. patient-centered endpoints). A better optimization of G/GEJ cancer treatment allows maximizing patient outcomes. In the perioperative phase, although caution is mandatory, times are changing and tailored strategies could introduce new treatment concepts. Overall, MSI-H G/GEJ cancer patients possess the characteristics to be the subgroup that could receive the most benefit from a tailored approach.

Case Report: Clinical application of continuous arterial infusion chemotherapy in neoadjuvant therapy for locally advanced gastric cancer

“…So, the treatment of gastric cancer in China is very challenging. Nearly 50% of patients still relapsed after surgery plus the standard regimen of perioperative platinum-based chemotherapy (24). Scholars attempted to get rid of the predicament of neoadjuvant chemotherapy for gastric cancer by adding new drugs.…”

Case Report: A rare case of recurrent ascites after anti-Claudin18.2 antibody therapy for metastatic gastric cancer while responding sustainingly

“…Gastric cancer remains one of the leading causes of cancer-related deaths worldwide, with more than 1.3 million deaths in 2020 (13% of all cancer deaths) ( 8 ). For patients with advanced stomach cancer who have no therapeutic target (e.g., Microsatellite Instability High, MSI-H, HER2 positive, CPS score≥5), the current treatment benefit is limited ( 9 ). Based on data from preclinical models and clinical samples, the anti-Claudin18.2 antibody emerged as a novel target therapy for stomach cancer ( 4 , 6 , 10 – 12 ).…”

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration

“…Even in resectable cases, the recurrence rates range from 14–80%, often exceeding 40% within the first years following surgery [ 126 , 127 ]. The addition of neoadjuvant therapy in surgical cases has slightly improved patient prognosis, but studies report recurrence rates exceeding 30% [ 128 , 129 , 130 ]. Unresectable cases present a dismal prognosis, with median overall survival rates ranging from 11 to 14 months, and 5-year survival rates of less than 30% [ 131 , 132 , 133 , 134 ].…”