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

Table 1 Comparison of representative biomarkers relevant to advanced gastric cancer

Biomarker	Main strength	Main limitation	Most appropriate clinical role at present	Ref.
PD-L1 CPS	Most widely used immunotherapy-enrichment marker	Heterogeneity, assay variability, imperfect negative predictive value	Treatment selection and contextual risk interpretation	[1,3,48,49,51]
MMR/MSI status	Strong biologic rationale and clinically actionable for a small subset	Low prevalence in advanced gastric cancer	Identification of highly immunotherapy-sensitive disease	[4,5,8]
HER2/claudin 18.2	Direct linkage to targeted treatment pathways	Does not capture host reserve or inflammatory state	Drug selection and sequencing	[50-52]
NLR/PLR	Simple inflammatory markers with extensive literature	Sensitive to transient hematologic fluctuations; limited nutritional context	Adjunctive prognostication and dynamic monitoring	[41-47]
Glasgow Prognostic Score	Established inflammation-based score	Categorical rather than continuous; less granular than CAR	Broad risk stratification	[45]
CAR	Integrates inflammation and nutrition in a cheap, universally available index	Nonspecific; threshold inconsistency; largely retrospective evidence	Complementary host-state biomarker integrated with tumor and clinical variables	[16,31,33,37-40]

PD-L1: Programmed death ligand 1; CPS: Combined positive score; MMR: Mismatch repair; MSI: Microsatellite instability; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; CAR: C-reactive protein/albumin ratio.

Table 2 Clinical interpretation of an elevated C-reactive protein/albumin ratio in advanced gastric cancer

Domain	What a high CAR may reflect	Potential implication during immunochemotherapy	Suggested complementary assessment	Ref.
Systemic inflammation	Tumor-promoted acute-phase response, cytokine activation, infection, or treatment-related inflammatory stress	Inferior immune fitness, greater risk of early progression, more difficult response interpretation	Clinical evaluation for infection, inflammatory comorbidity review, CRP trend rather than single value	[10,11,38,60,61]
Nutritional depletion	Reduced intake, gastric outlet dysfunction, weight loss, hypoalbuminemia, impaired hepatic protein synthesis	Lower treatment tolerance, greater dose intensity reduction risk, slower recovery from adverse events	Dietitian referral, body-weight history, oral intake assessment, GLIM or equivalent nutrition screening	[12,17-20]
Cachexia/catabolism	Persistent inflammation with muscle and functional decline	Reduced resilience, fatigue, poorer quality of life, shortened survival	Body composition review, handgrip or gait assessment where available, early supportive care	[13-15]
High tumor burden/aggressive disease	Extensive metastatic burden, peritoneal disease, biologically active tumor-host interaction	Rapid clinical deterioration and compressed therapeutic window	Metastatic pattern review, symptom burden assessment, early restaging planning	[9,39,53-56]
Dynamic treatment state	Failure of inflammation to improve or progressive albumin decline during therapy	Possible early treatment failure or clinically meaningful toxicity	Serial CAR measurement together with symptoms, imaging, and treatment exposure	[39,40,57-60]

CAR: C-reactive protein/albumin ratio; CRP: C-reactive protein; GLIM: Global Leadership Initiative on Malnutrition.