Emotional distress and pathological response to neoadjuvant immunotherapy in locally advanced gastric cancer: a multicentre retrospective cohort study

To investigate the association between emotional distress (ED) and pathological response to neoadjuvant immune checkpoint inhibitor (ICI)-based therapy in patients with locally advanced gastric cancer (GC). In this retrospective cohort study (April 2022–December 2024), 129 advanced GC patients receiving neoadjuvant anti-PD-1 therapy were included from two Chinese hospitals. ED was assessed using validated scales (PHQ-9 and GAD-7). ED was defined as a PHQ-9 score ≥ 5 or a GAD-7 score ≥ 5. Outcomes included pathological response (assessed by CAP-TRG) and its correlation with perineural invasion (PNI). Statistical analyses comprised chi-square tests for categorical comparisons and logistic regression to identify independent factors associated with treatment response. Among 129 patients, 38.0% (49/129) exhibited ED. ED patients showed significantly lower immunotherapy response rates than non-ED patients (36.7% vs. 81.3%; P < 0.001). Multivariate logistic regression confirmed ED as an independent negative predictor of response (adjusted OR = 0.252, 95% CI: 0.076–0.809, P = 0.021). ED correlated with higher PNI prevalence (77.8% vs. 26.5%; P < 0.001). Furthermore, within the PD-L1 CPS ≥ 5 subgroup, non-ED patients maintained superior treatment response compared to ED patients. ED is associated with poorer pathological response to neoadjuvant ICI-based therapy in locally advanced GC, potentially through its correlation with PNI. These findings suggest that ED is a potential host-related factor associated with ICI response and highlight the need for psychological support in this population. Prospective studies are warranted to validate the underlying mechanisms and clinical utility.