Perioperative Immune Checkpoint Inhibitors for the Treatment of Locally Advanced Gastric and Gastroesophageal Junction Cancer: Current Status and Future Prospects.

Opinion statement: Novel strategies utilizing immune checkpoint inhibitors (ICIs) have emerged over the past several years and substantially changed the treatment landscape of advanced gastric cancer (GC). Based on the encouraging results achieved, numerous clinical studies have been conducted to identify the feasibility and efficacy of integrating ICIs into the perioperative treatment of locally advanced gastric and gastroesophageal junction cancer (GC/GEJC). Initial clinical trials have indicated that the addition of immunotherapy to chemotherapy, concurrent chemoradiotherapy, or chemotherapy combined with anti-angiogenic therapy in the perioperative setting significantly improves the pathological remission of patients, thereby promising to improve the prognosis. However, in the absence of strong evidence from long-term follow-up data, these approaches have yet to be entirely translated into clinical practice. Therefore, it is recommended that the aforementioned patients be prioritized for participation in clinical trials. In addition, based on the negative results of ATTRACTION-05, current evidence does not support the use of adjuvant immunotherapy in patients without neoadjuvant immunotherapy. For patients with dMMR/MSI-H disease, neoadjuvant immunotherapy has demonstrated excellent pCR rates, and the 2024 NCCN guidelines have recommended neoadjuvant or perioperative ICIs for these patients. In HER2-positive locally advanced GC/GEJC, neoadjuvant dual PD-1 and HER2 inhibition combined with chemotherapy has also shown promising prospects. However, the development of perioperative ICIs has also posed formidable therapeutic challenges. Given the high heterogeneity of GC, there is an urgent need to select patients likely to benefit from ICIs with precision through microenvironment analysis, molecular biomarker screening, and clinical subgroup analysis. In parallel, the benefits of ICIs in locally advanced GC/GEJC should be carefully weighed against their associated adverse effects and significant financial toxicity.