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.

Key Words: 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.

INTRODUCTION

With the incorporation of immune checkpoint inhibitors into first-line treatment, the therapeutic landscape of advanced gastric adenocarcinoma has changed substantially. Studies such as CheckMate 649, ATTRACTION-4, KEYNOTE-859, and ORIENT-16 have confirmed that, in selected populations, programmed death-1 (PD-1) blockade combined with chemotherapy can improve survival outcomes; however, the magnitude of benefit still varies across subgroups defined by different clinical and biomarker characteristics[1-4]. Early studies of pembrolizumab also showed that the benefit of immunotherapy in gastric cancer is conditional, context-dependent, and strongly influenced by biological heterogeneity, particularly programmed death ligand 1 (PD-L1) expression and mismatch repair status[5-8]. Even though Immunochemotherapy has become part of standard treatment, primary and acquired resistance remain common, and many patients still experience early progression or only limited durable benefit[9].

Against this background, host-derived biomarkers are becoming increasingly important. Although tumor-centered predictive markers remain essential for treatment selection, they are still insufficient to fully explain why patients with apparently similar PD-L1 status, stage, or treatment exposure may ultimately experience markedly different clinical outcomes. Advanced gastric cancer is not merely a metastatic disease confined to the tumor itself, but a complex systemic disease deeply shaped by host responses. Inflammation, nutritional depletion, cachexia, sarcopenia, activation of hepatic acute-phase response pathways, and impaired immune competence may all jointly influence disease progression and further affect the balance between benefit and risk during Immunochemotherapy[10-15].

Within this context, the recent study by Mei et al[16] has brought the CAR to the forefront. They reported that baseline CAR is independently associated with progression-free survival, overall survival, and treatment response in patients with advanced gastric cancer receiving first-line immunochemotherapy[16]. This finding not only suggests a statistical association, but also gives CAR broader clinical and biological relevance: In the immunotherapy era, prognostic assessment should no longer be viewed simply as a binary contrast between tumor biomarkers and host biomarkers. Rather, the real challenge is to build integrated models that combine tumor biology with host biology, thereby providing a more accurate explanation for interpatient differences in treatment benefit and thereby improving individualized treatment decision-making in the context of rapid clinical deterioration and a compressed therapeutic window.

BIOLOGICAL RATIONALE OF CAR IN IMMUNOCHEMOTHERAPY

CAR integrates two laboratory parameters, C-reactive protein (CRP) and serum albumin, and therefore has considerable clinical interpretability. Unlike an isolated laboratory abnormality, an elevated CAR usually indicates that the patient is experiencing both inflammatory activation and nutritional impairment at the same time[10-12]. This feature makes it more than a simple biochemical ratio; it may instead reflect a broader imbalance in the overall physiological state of the host. CRP is not merely a passive marker of inflammation. Experimental and translational studies have shown that elevated CRP is often associated with impaired adaptive immunity, T-cell dysfunction, and a systemic immunosuppressive state, all of which could theoretically weaken the therapeutic effect of immune checkpoint blockade[10,11]. Albumin, meanwhile, should not be regarded solely as a surrogate marker of nutrition. Low albumin often indicates persistent chronic inflammation and may accompany increased capillary permeability, altered protein turnover, reduced intake, and cachexia-related metabolic remodeling[12-15].

This biological phenomenon is particularly relevant in gastric cancer. Patients with gastric cancer often face multiple overlapping problems, including appetite loss, obstructive gastrointestinal symptoms, prior gastrectomy or bypass surgery, peritoneal metastasis, ascites, chronic blood loss, and treatment-related toxicity. Together, these factors may converge to produce a complex syndrome of inflammation and malnutrition. Modern clinical nutrition frameworks, such as the ESPEN recommendations and the Global Leadership Initiative on Malnutrition (GLIM) criteria, also emphasize that inflammation and malnutrition are biologically intertwined rather than analytically separable processes[15-20]. From this perspective, the importance of CAR lies not in its simplicity alone, but in its ability to condense a clinically real and complex host condition into a usable biomarker.

Evidence from other malignancies also supports the biological plausibility of CAR. Before it was widely studied in gastric cancer, CAR had already been evaluated as an inflammation-based prognostic marker in hepatocellular carcinoma, palliative care populations, and other solid tumor cohorts[21-23]. Although these studies do not prove that CAR is specific to gastric cancer, they suggest that CAR may represent a broader phenotype of host vulnerability. In diseases such as advanced gastric cancer, where inflammatory burden and nutritional deterioration are both prominent, this phenotype may be further amplified, making CAR more likely to serve as a clinically relevant host-related indicator of prognosis and Immunochemotherapy outcomes.

CLINICAL EVIDENCE FOR CAR OUTSIDE IMMUNOCHEMOTHERAPY

The use of CAR in gastric cancer did not begin in the era of Immunochemotherapy. Earlier studies consistently showed that elevated baseline CAR was associated with poorer survival outcomes across several settings, including patients undergoing curative resection, patients with metastatic disease treated with cytotoxic chemotherapy, and patients with upper gastric or gastroesophageal junction tumors that differ anatomically but share related biological features[24-30]. Although these studies varied in terms of patient populations, disease stage, treatment modality, and cut-off definitions, the overall direction of their findings was highly consistent: Patients with higher CAR generally had more unfavorable clinicopathological characteristics, poorer treatment tolerance, and shorter survival.

Meta-analyses have further strengthened this association. Studies by Yang et al[31] and Yue et al[33] both showed that elevated baseline CAR was significantly associated with worse overall survival and disease-free survival in patients with gastric cancer. A clinicopathological study by Yue et al[33] in 2021 further suggested that CAR was associated with tumor burden and retained prognostic value beyond conventional staging information[32]. In addition, other retrospective studies indicated that CAR may remain clinically relevant at different points along the disease course, including in patients with stage II/III disease, in those receiving later-line trifluridine/tipiracil treatment, and in the assessment of dynamic changes in CAR before and after treatment[34-36].

The pre-immunochemotherapy literature remains highly informative. On the one hand, these studies suggest that the association between CAR and prognosis is not an incidental finding limited to a particular treatment era, but rather a relatively stable phenomenon across different therapeutic contexts. On the other hand, they also remind us to remain cautious when interpreting CAR and not to regard it directly as an immunotherapy-specific biomarker. Current evidence more strongly supports the idea that CAR reflects a broader disturbance in host condition, including systemic inflammation, nutritional decline, cancer-related catabolism, and overall frailty. This does not diminish the clinical relevance of CAR; rather, it suggests that its value may lie precisely in capturing the host factors that influence treatment outcomes. At the same time, however, any claim that CAR has true treatment-specific predictive value will require stronger and higher-level evidence than is currently available from most retrospective studies.

INTERACTION BETWEEN CAR AND IMMUNOCHEMOTHERAPY

With the increasing use of PD-1 inhibitor-based combination therapy, the clinical meaning of CAR needs to be reconsidered within this new treatment context. In the setting of Immunochemotherapy, an elevated CAR may reflect several overlapping processes. It may indicate a more pronounced state of systemic inflammation and immune dysregulation, a host environment that may be unfavorable for mounting an effective antitumor immune response. It may also reflect poorer physiological reserve and nutritional status, thereby reducing tolerance to combination therapy and limiting the ability to complete a sufficient duration of treatment to achieve cumulative benefit. In addition, CAR may partly capture the combined effect of aggressive tumor biology and host metabolic imbalance, a state that is often associated with more rapid clinical deterioration. Meta-analyses in solid tumors treated with immune checkpoint inhibitors have likewise shown a stable association between elevated CAR and poorer survival outcomes, suggesting that this host-derived signal is not restricted to gastric cancer[37,38].

In gastric cancer, relevant evidence is beginning to accumulate, but the field remains at an early stage. Recent retrospective analyses by Mei et al[16] suggest that baseline CAR and other related inflammatory markers may help stratify outcomes in patients receiving first-line PD-1 inhibitor-based therapy[1,39,40]. At the same time, parallel studies of the neutrophil-to-lymphocyte ratio (NLR) in metastatic gastric cancer and upper gastrointestinal cancers, as well as meta-analyses in gastric cancer cohorts treated with immunotherapy, further support the prognostic relevance of systemic inflammatory indices in this treatment context (Figure 1)[41-44].

Figure 1 Schematic of the implications of elevated C-reactive protein/albumin ratio in advanced gastric cancer receiving immunochemotherapy. The figure included in this manuscript was created by the authors using BioRender. An elevated C-reactive protein/albumin ratio reflects increased systemic inflammation and reduced albumin levels, and is associated with immune dysregulation, poor physiological and nutritional status, and aggressive tumor and metabolic features. These changes may contribute to reduced treatment tolerance, rapid clinical deterioration, and poor prognosis. C-reactive protein/albumin ratio should be interpreted primarily as a prognostic marker rather than a treatment-specific predictive marker, highlighting the need for further validation in immunochemotherapy settings. CAR: C-reactive protein/albumin ratio; PD-1: Programmed death-1.

Even so, caution remains necessary when defining the role of CAR at present. Based on current evidence, it is more appropriate to view CAR as a prognostic marker rather than a predictive marker. Most available studies lack a rigorous chemotherapy-only control group, and sample sizes are generally limited. As a result, it is still unclear whether elevated CAR indicates reduced benefit from immunotherapy specifically, or simply reflects poorer baseline condition, which itself would be associated with worse outcomes regardless of whether immunotherapy is given. This distinction is methodologically important. A biomarker associated with poor prognosis is not necessarily a biomarker that predicts lack of benefit from PD-1 blockade. These concepts should therefore not be used interchangeably when interpreting the current evidence.

An elevated CAR reflects increased systemic inflammation and reduced albumin levels, and is associated with immune dysregulation, poor physiological and nutritional status, and aggressive tumor and metabolic features. These changes may contribute to reduced treatment tolerance, rapid clinical deterioration, and poor prognosis. CAR should be interpreted primarily as a prognostic marker rather than a treatment-specific predictive marker, highlighting the need for further validation in immunochemotherapy settings.

INTERACTION BETWEEN CAR AND OTHER BIOMARKERS

In clinical practice, the more relevant question is not whether CAR has value in absolute terms, but whether it can provide additional information beyond existing biomarkers. At present, tumor-centered biomarkers such as PD-L1, deficient mismatch repair/microsatellite instability, HER2, Epstein-Barr virus status, and Claudin 18.2 remain critically important because they are more directly linked to treatment selection and are increasingly tied to approved targeted or immunotherapeutic agents[48-52]. However, these biomarkers mainly reflect the biological characteristics of the tumor itself and often fail to capture the patient’s overall condition, including malnutrition, systemic inflammation, risk of sarcopenia, cachexia, and treatment tolerance. This gap helps explain the continued interest in host-derived inflammatory and nutritional indices such as CAR, the Glasgow Prognostic Score, NLR, and the platelet-to-lymphocyte ratio[45-47].

Compared with these markers, CAR has several practical advantages. It is simple to calculate, easy to obtain, inexpensive, and applicable in almost any clinical setting. At the same time, it combines inflammatory and nutritional status into a single index, making its clinical interpretation relatively intuitive. The Glasgow Prognostic Score is also based on CRP and albumin, but uses a categorical scoring system; while this increases simplicity, it also sacrifices some granularity[45]. NLR is similarly easy to obtain and widely used in oncology research, but it is more susceptible to short-term hematologic fluctuations and is less direct than CAR in reflecting nutritional vulnerability. By contrast, more comprehensive nutritional assessment frameworks such as GLIM provide richer clinical information, but they usually require data on weight change, body composition, or more structured phenotypic assessment, which are difficult to standardize in large retrospective datasets[16-20].

For these reasons, CAR is best viewed not as a replacement for other biomarkers, but as a complementary marker that bridges tumor characteristics and host status. Its value lies in helping identify patients whose biological condition is shaped by both inflammation and malnutrition, thereby prompting clinicians to further evaluate overall host status before or during treatment. In an ideal assessment model, CAR should be interpreted alongside PD-L1, mismatch repair status, metastatic pattern, performance status, and, where available, body composition measures, rather than competing with them. The distinct but complementary roles of CAR and other representative biomarkers relevant to advanced gastric cancer Immunochemotherapy are summarized in Table 1. This comparison further supports the view that CAR should be integrated with, rather than substituted for, tumor-centered biomarkers in clinical decision-making.

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.

LIMITATIONS OF CAR APPLICATION

Although CAR is attractive because it is easy to obtain, inexpensive, and straightforward to interpret, its application still has several important limitations. Most existing evidence comes from retrospective, single-center studies and is therefore vulnerable to selection bias, insufficient control of confounding factors, and variation in supportive care exposure. In addition, different studies often use data-driven approaches to define cut-off values, resulting in substantial variation in thresholds across studies and weakening reproducibility across populations. For this reason, CAR is not yet suitable to be used directly as a universal clinical decision-making standard[31-40]. From a biological standpoint, CAR also lacks specificity. Elevated CRP may be caused not only by tumor-related inflammation, but also by infection, biliary inflammation, treatment toxicity, postoperative complications, or autoimmune disease. Likewise, low albumin may be influenced by liver dysfunction, renal disease, protein loss, fluid overload, and systemic catabolism. In routine gastric cancer practice, these conditions are common rather than exceptional. As a result, an elevated CAR should be interpreted as a clinical signal that warrants further assessment, rather than as a marker that can be applied mechanically. At the same time, CAR itself combines multiple layers of information: It may reflect tumor burden, reduced host reserve, and systemic inflammatory activation all at once. This contributes to its prognostic sensitivity, but also makes its biological meaning less clear. In other words, it is often difficult at present to determine whether a high CAR mainly reflects more aggressive tumor biology, poorer host condition, or both[10,53-56]. Furthermore, most current studies assess CAR only at a single pretreatment time point, whereas Immunochemotherapy is inherently dynamic. A patient’s inflammatory and nutritional state may change continuously with treatment response, disease progression, and supportive care, meaning that a single baseline measurement is unlikely to fully capture the evolving host–tumor interaction. Taken together, CAR is best regarded as a potentially valuable but cautiously interpretable adjunctive marker, rather than a decisive biomarker that can be used independently of clinical context.

A PERSPECTIVE-BASED CLINICAL FRAMEWORK FOR CAR APPLICATION

In current clinical practice, CAR should not be used as a reason to withhold standard Immunochemotherapy from otherwise eligible patients. The available evidence is still insufficient to support its use as a treatment entry or exclusion criterion. A more reasonable approach is to view a clearly elevated CAR as a warning signal that should prompt a more comprehensive baseline assessment before treatment begins. At a minimum, this assessment should include renewed evaluation for infection or occult inflammatory processes, performance status, recent weight change, oral intake, metastatic burden, ascites, and baseline nutritional risk. In centers with greater resources, this may be complemented by assessment of sarcopenia, GLIM-based nutritional evaluation, or pretreatment optimization involving dietitians, allowing a more complete understanding of host status[17-20]. To make this clinical interpretation more practical, the potential implications of an elevated CAR and the corresponding complementary assessments are summarized in Table 2.

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.

The practical value of CAR is also reflected in patient management and follow-up. Existing evidence suggests that patients with higher CAR are more likely to experience early progression, poorer treatment tolerance, or limited durable benefit. In such patients, clinicians may consider closer monitoring, including earlier imaging reassessment, more proactive symptom surveillance, and earlier incorporation of supportive care, rehabilitation, and nutritional intervention. Importantly, this does not mean reducing treatment simply because CAR is high; rather, it suggests that these patients may require more intensive supportive care. In other words, a high CAR should trigger more active management, not a more nihilistic treatment attitude. At the same time, from a developmental perspective, CAR may ultimately prove more useful as a dynamic monitoring tool than as a one-time pretreatment measure. Immunochemotherapy is a continuously evolving process, and inflammatory and nutritional states may shift with treatment response, disease progression, and supportive intervention. Compared with a single baseline value, early changes in CAR during treatment may better reflect the patient’s real-time response. Long-term follow-up from pivotal clinical trials and emerging real-world analyses have shown that not all patients derive durable benefit from PD-1-based combination therapy, further underscoring the need for simple dynamic biomarkers that can identify early divergence in outcome trajectories[57-60]. Accordingly, if interpreted in conjunction with serial measurements and overall clinical status, CAR may eventually be more useful as a treatment-monitoring tool than as a pretreatment decision threshold.

FUTURE DIRECTIONS

Future research on CAR should move beyond simply demonstrating an association with outcomes and instead focus more closely on how CAR can be used clinically and whether it can guide meaningful interventions. One of the most important current priorities is to validate prespecified CAR thresholds in prospective multicenter studies, rather than redefining the “optimal” cut-off in each dataset, because only then will the findings be more reproducible and more relevant to real-world clinical practice. At the same time, future study designs should pay greater attention to distinguishing the prognostic value of CAR from its predictive value. By including appropriate comparison groups, such as chemotherapy-only control cohorts or stratified randomized datasets, investigators may be able to clarify whether CAR simply identifies patients with poorer overall outcomes or truly identifies those who derive less benefit from immunotherapy.

In addition, CAR should not be studied only as a static pretreatment marker. Greater attention should be directed toward its dynamic changes during therapy. Evaluating serial CAR changes in relation to radiologic response, immune-related adverse events, nutritional interventions, treatment tolerance, and long-term survival outcomes may provide a more meaningful understanding of its clinical role. In parallel, translational research is needed to further clarify the biology underlying CAR, including its relationship with circulating cytokines, myeloid inflammation, cachexia pathways, sarcopenia, and the tumor immune microenvironment in gastric cancer[53-56,61,62]. Only by clarifying these mechanistic links can CAR evolve from an empirical index into a more interpretable clinical tool.

An even more important, yet still underexplored, next step is interventional research. If CAR is clinically relevant because it reflects host inflammatory activation and nutritional impairment, future work should not stop at risk stratification alone. It should also determine whether interventions targeting these abnormalities can improve clinical outcomes. Multimodal supportive care, immunonutrition, exercise-based prehabilitation or rehabilitation, early dietitian involvement, and rational anti-inflammatory strategies all represent plausible approaches; however, these interventions remain insufficiently evaluated in biomarker-stratified gastric cancer populations[18-20,63,64]. In this context, the most promising future role of CAR may lie not merely in serving as another prognostic variable in a nomogram, but in functioning as an actionable entry point that links systemic anticancer therapy with supportive care, thereby enabling earlier identification of high-risk patients and more timely implementation of individualized, comprehensive management.

Recent literature also suggests that the next phase of CAR research should be embedded within broader host- and systems-level assessment. Gastric cancer-specific reviews increasingly emphasize longitudinal nutritional evaluation, proactive dietitian involvement, and peri-treatment optimization across both perioperative and advanced-disease settings[65-72]. In parallel, sarcopenia- and body-composition-based studies indicate that host fitness markers may complement inflammatory indices when estimating treatment tolerance, toxicity risk, and immunotherapy outcomes[73-79]. Emerging work on ctDNA, Epstein-Barr virus-associated biology, and biomarker-testing frameworks further suggests that future prediction models will need to combine host-derived markers such as CAR with dynamic molecular monitoring rather than rely on any single variable in isolation[80-84].

CONCLUSION

CAR is one of the most clinically plausible host-derived biomarkers currently under discussion in the field of Immunochemotherapy for advanced gastric cancer. Its appeal lies in its simplicity, low cost, biological plausibility, and ability to capture a dimension of cancer treatment that is often underrecognized: The host inflammatory-nutritional state. We believe that the current literature supports CAR as a complementary prognostic tool, but not yet as an independent predictive biomarker or a decision threshold for treatment selection. The most credible next step is the integrative use of CAR in combination with molecular biomarkers, metastatic pattern, and structured nutritional assessment, while the field moves toward prospective validation and intervention-based research. If these efforts are pursued rigorously, CAR may help shift gastric cancer treatment from a narrow tumor-only model toward a more clinically realistic tumor-host model.