C-reactive protein/albumin ratio in immunochemotherapy for advanced gastric cancer: Prognostic value, clinical challenges, and future directions

Abstract

The C-reactive protein/albumin ratio (CAR) has emerged as a practical host-derived biomarker that has attracted increasing attention in advanced gastric cancer in recent years. Its main strength lies in integrating two clinically important dimensions - systemic inflammation and nutritional reserve - into a low-cost, readily available indicator. In the era of Immunochemotherapy, although programmed death-1-based first-line regimens have improved outcomes for some patients with advanced gastric or gastroesophageal junction adenocarcinoma, treatment benefit remains markedly heterogeneous, and current decision-making tools still rely largely on tumor-centric variables. Against this background, CAR, as an indicator of overall host status, deserves further investigation. CAR may capture biological states related to cancer-associated inflammation, metabolic stress, cachexia, impaired treatment tolerance, and immune dysfunction, aspects that are often not fully reflected by programmed death ligand 1 expression, mismatch repair status, or anatomic features alone. However, current evidence on CAR is derived mainly from retrospective studies, and many studies have used data-driven approaches to define cut-off values, leaving the boundary between its prognostic value and true predictive value unclear. In addition, CAR is susceptible to confounding by infection, liver dysfunction, coexisting inflammatory conditions, and differences in supportive care. On this basis, we argue that CAR should not currently be regarded as an independent basis for Immunochemotherapy decision-making. Rather, its more reliable near-term role is as a complementary biomarker of host status that can help refine baseline risk stratification, support the assessment of nutritional and inflammatory status, and contribute to dynamic monitoring during treatment when integrated with molecular and clinical biomarkers. Future studies should focus on prospective multicenter validation, standardized threshold setting, longitudinal dynamic analyses, biological links with the tumor immune microenvironment, and whether CAR-guided supportive care strategies can truly improve patient outcomes.

Keywords: Gastric cancer; C-reactive protein-to-albumin ratio; Immunochemotherapy; Prognosis; Inflammation; Nutrition

Core Tip: C-reactive protein/albumin ratio (CAR) has attracted attention because it is easy to obtain, highly reproducible in clinical practice, and biologically linked to systemic inflammation, malnutrition, cachexia, treatment tolerance, and immune competence. We argue that, in Immunochemotherapy for advanced gastric cancer, the greatest value of CAR is not as an independent determinant of treatment selection, but as a complementary host-state biomarker that should be interpreted alongside programmed death ligand 1, mismatch repair status, metastatic burden, and performance status. The field now needs prospective validation, dynamic monitoring of CAR, and clinical trials testing whether CAR-guided nutritional or anti-inflammatory interventions can improve clinically meaningful outcomes.