Prognostic significance of baseline C-reactive protein/albumin ratio for long-term outcomes in advanced gastric cancer under immunochemotherapy

Abstract

BACKGROUND

Patients with advanced gastric cancer typically exhibit a dismal prognosis. Although combined immunotherapy and chemotherapy have been shown to improve survival in a subset of patients, substantial interindividual heterogeneity in therapeutic response persists, and reliable, easily obtainable prognostic biomarkers remain limited. The C-reactive protein/albumin ratio (CAR), a composite indicator of systemic inflammation and nutritional status, has demonstrated prognostic relevance across multiple malignancies. Nevertheless, its long-term prognostic significance in advanced gastric cancer patients receiving combined immunochemotherapy has not yet been clearly defined.

AIM

To assess baseline CAR’s prognostic value and develop a model for guiding personalized immunochemotherapy in advanced gastric cancer.

METHODS

Retrospectively, we collected clinical data from 200 advanced gastric cancer patients treated with first-line immunochemotherapy at the Affiliated Hospital of Xuzhou Medical University. The optimal CAR cutoff was determined by receiver operating characteristic curve (ROC) analysis, stratifying patients into high and low CAR groups. Survival was assessed using the Kaplan-Meier method and compared with the log-rank test. Cox regression evaluated CAR’s association with progression-free survival (PFS) and overall survival (OS). A prognostic nomogram was then constructed based on significant factors.

RESULTS

ROC curve analysis showed that the baseline CAR had an area under the curve of 0.80 [95% confidence intervals (CI): 0.76-0.85] for predicting OS, with an optimal cutoff value of 0.21. Based on this threshold, patients were stratified into a low CAR group (CAR < 0.21; n = 120) and a high CAR group (CAR ≥ 0.21; n = 80). The low CAR group exhibited a significantly longer median PFS of 12.3 months (95%CI: 9.5-21.0) compared with 7.2 months (95%CI: 6.2-9.8) in the high CAR group (P = 0.0023). Similarly, the median OS was markedly prolonged in the low CAR group (20.4 months; 95%CI: 18.5-25.1) relative to the high CAR group (14.3 months; 95%CI: 13.4-16.1; P < 0.001). The low CAR group also demonstrated superior objective response rate (ORR) and disease control rate (DCR), at 59.17% and 79.17%, respectively, compared with 45.00% and 66.25% in the high CAR group (P = 0.049; P = 0.041). Multivariate Cox regression analysis identified baseline CAR, programmed death-ligand 1 expression, mismatch repair status, tumor stage, and peritoneal metastasis as independent prognostic factors for both PFS and OS. A prognostic column-plot model integrating these variables exhibited robust discriminative ability and calibration in both the training and validation cohorts, with C-indices of 0.80 and 0.82 for PFS, and 0.78 and 0.73 for OS, respectively.

CONCLUSION

The baseline CAR index is an independent prognostic factor for long-term outcomes in advanced gastric cancer patients treated with combination immunotherapy and chemotherapy. Lower CAR levels correlate with improved PFS, OS, and higher ORR and DCR. The calibration curve model, incorporating CAR and clinical-pathological factors, demonstrates strong predictive performance, providing valuable insights for prognosis and personalized treatment.

Keywords: Gastric cancer; C-reactive protein/albumin ratio; Programmed death-1 inhibitor; Predictive model; Efficacy; Safety

Core Tip: The baseline C-reactive protein/albumin ratio (CAR) is a significant independent prognostic factor for advanced gastric cancer patients receiving combination immunotherapy and chemotherapy, with lower CAR levels associated with improved progression-free survival, overall survival, and higher objective response and disease control rates. By incorporating both inflammatory and nutritional status, the CAR index provides a more comprehensive evaluation of the immune microenvironment compared to traditional single inflammatory biomarkers. The CAR-integrated nomogram shows strong predictive accuracy, guiding personalized immunotherapy strategies. However, prospective, multi-center studies are needed to validate and refine its clinical applicability.