Geriatric Nutritional Risk Index is an effective prognostic predictor for metastatic/recurrent or unresectable esophageal cancer receiving immunotherapy.

Background: Immune checkpoint inhibitors (ICIs) have been extensively utilized in the treatment of esophageal squamous cell carcinoma (ESCC); however, patient responses to these therapies exhibit significant variability. This study aimed to investigate the prognostic value of Geriatric Nutritional Risk Index (GNRI) in patients with ESCC undergoing immunotherapy. Methods: A retrospective study was conducted on 677 patients with metastatic/recurrent or unresectable ESCC who received immunotherapy. Kaplan-Meier analysis and Log-rank test compared survival differences between high and low GNRI groups, while Cox proportional hazards models analyzed the impact of GNRI on survival in various subgroups and identified independent prognostic factors. Furthermore, immunohistochemistry (IHC) was performed on endoscopic biopsy tissues from 45 patients with unresectable disease who received immune ICIs as first-line treatments to investigate the predictive performance of GNRI combined with programmed cell death ligand 1 (PD-L1) for tumor response and overall survival (OS). Results: Regardless of metastatic/recurrent disease or unresectable status, patients with high GNRI levels had significantly longer OS time (P<0.001). Moreover, the protective role of GNRI was observed in various subgroups. Eastern Cooperative Oncology Group performance status (ECOG PS) score, distant organ metastasis, previous treatments, ICI modalities and GNRI were identified as independent prognostic factors for OS. Furthermore, the predictive performance of GNRI for OS may surpass that of PD-L1 expression (P=0.009 Conclusions: The GNRI serves as a robust prognostic indicator in patients with ESCC who are treated with ICIs. The integration of PD-L1 expression and GNRI demonstrates significant predictive value for tumor response and OS.