Table of Contents
- Key Points
- Background: Why This Research Matters
- What Is Sarcopenia?
- How the Research Was Conducted
- How Study Quality Was Assessed
- Key Finding: How Common Is Sarcopenia in Stomach Cancer?
- Risk Factor: Age
- Risk Factor: Gender
- Risk Factor: Body Mass Index
- Risk Factor: Tumor Diameter
- Risk Factor: Nutritional Risk
- Factors With No Significant Link
- Understanding the Differences Between Studies
- What This Means for Patients
- Limitations of This Research
- Recommendations
- Frequently Asked Questions
- Source Information
Key Points
- In a combined analysis of 20 studies with 4,782 gastric cancer patients, about 26.6% also had sarcopenia, meaning roughly 1 in 4.
- The strongest risk factor was an NRS2002 nutritional risk score above 3, which raised the odds of sarcopenia nearly fourfold.
- Age over 65, male sex, low body mass index, and tumors larger than 3 centimeters were also linked to higher sarcopenia risk.
- Tumor stage, type of surgery, tumor differentiation, and severe chemotherapy side effects showed no statistically significant connection to sarcopenia.
- The analysis focused mainly on Asian populations, and the researchers recommend screening all gastric cancer patients, especially those over 65.
Background: Why This Research Matters
Sarcopenia (severe loss of muscle mass and muscle function) is a progressive, whole-body muscle disease. It is most often linked to aging. However, many other conditions can also cause it, including cancer, organ failure, chronic infections, and the aging process itself. These conditions can severely damage the structure and function of skeletal muscle.
When sarcopenia is caused by another disease rather than by aging alone, doctors call it secondary sarcopenia. The incidence of secondary sarcopenia is much higher than that of primary sarcopenia. This is especially true for patients with gastrointestinal tumors (cancers of the digestive system).
Gastric cancer (stomach cancer) is one of the most common gastrointestinal tumors worldwide. It ranks fifth in global incidence and fourth in global mortality. This means it poses a serious threat to human health. Gastric cancer develops from a combination of genetic, environmental, and biological factors.
Muscle mass plays an extremely important role in the treatment of gastric cancer. One study found that the main cause of death in gastric cancer patients is postoperative sarcopenia (muscle loss after surgery), not the cancer itself. This finding highlights how critical muscle health is for these patients.
The reported incidence of sarcopenia in gastric cancer patients varies widely depending on which diagnostic criteria are used. According to the European Working Group on Sarcopenia in Old People (EWGSOP) criteria published in 2010 and 2019, the incidence was 17% and 19%, respectively. Another study reported a prevalence of 30.5%.
As the number of gastric cancer cases rises, sarcopenia in these patients is receiving much more attention. However, the exact causes of sarcopenia in gastric cancer are complicated. The incidence differs across tumor stages and tumor sizes. This variation may be due to differences in how patients are selected, which evaluation criteria are used, and the baseline characteristics of the patients.
Many studies have investigated how sarcopenia affects the prognosis (likely outcome) of gastric cancer patients. However, there is a lack of evidence to predict which patients will develop sarcopenia. This gap has become an important clinical issue. This paper reviews the incidence and risk factors of sarcopenia in gastric cancer patients.
What Is Sarcopenia?
Sarcopenia is now officially recognized as a muscle disease in the International Classification of Diseases (ICD-10: M62). Multiple biological mechanisms may be involved in its onset and progression.
In patients with sarcopenia, muscle wasting is thought to interact with systemic inflammation (widespread inflammation throughout the body), immune dysfunction, and nutritional deficiencies. Muscle loss changes over time. The measurable variables are muscle mass, muscle strength, and physical performance.
Because these variables change over time, diagnostic criteria are still lacking. The most commonly used definitions come from three groups:
- The European Working Group on Sarcopenia in Old People, 2010 version (EWGSOP2010)
- The revised European Working Group criteria, 2019 version (EWGSOP2)
- The Asian Working Group on Sarcopenia (AWGS)
According to the AWGS 2010 version, sarcopenia is defined only by low muscle mass. This definition does not reflect muscle function. The 2019 version is now commonly used and has different thresholds for Asian populations.
One meta-analysis found that the prevalence of sarcopenia was 10% in individuals over 60 years old. That figure increased to 20% when the diagnosis was made using bioelectrical impedance analysis (BIA, a method that measures body composition by passing a small electrical current through the body). Another study reported that the prevalence of sarcopenia in gastric cancer patients ranged from 12.5% to 69.8%.
However, another meta-analysis of 58,404 community residents aged 60 years and older estimated that the overall prevalence of sarcopenia was 10%. Compared to dual-energy X-ray absorptiometry (DXA, a scan that measures bone and muscle density), the overall prevalence was slightly higher when muscle mass was measured using BIA.
How the Research Was Conducted
This systematic review and meta-analysis followed the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The study was registered with the International Prospective Register of Systematic Reviews (registration number CRD42023446996).
The researchers searched seven databases: PubMed, Embase, Cochrane, Web of Science, CNKI, Wanfang, and VIP. The search was limited to studies published in Chinese or English. The search covered case-control studies and cohort studies published up to September 1, 2023.
The search used medical subject headings (MeSH terms) for gastric cancer, sarcopenia, and risk factors. Two researchers, Fu Mingyue and Zhou Jing, performed the literature search independently. Any disagreements were resolved through discussion with Wang Xuehong. The researchers also reviewed the reference lists of relevant articles to find additional eligible studies.
The inclusion criteria were formulated according to the PICOS principle (Population, Intervention, Comparison, Outcomes, Study design). The included studies analyzed risk factors and clinical effects of sarcopenia on the prognosis of gastric cancer patients. Patients in the studies had gastric cancer with or without sarcopenia.
The exposure factors examined were population characteristics such as sex, age, and other health conditions. The outcome measure was the association of these risk factors with sarcopenia in gastric cancer patients, reported with 95% confidence intervals (CI).
The types of studies included were retrospective studies (looking back at existing records) and randomized clinical trials (RCTs). The researchers excluded studies for the following reasons:
- The full text could not be obtained or the original research data could not be extracted
- Case report abstracts, conference papers, reviews, and meta-analyses
- Repeatedly published literature
- Animal experiments
Two investigators independently reviewed the titles and abstracts of all retrieved studies. Studies that met the inclusion criteria were selected for full-text assessment. All data were recorded on a pre-designed table.
The extracted information included the first author, date and country of publication, and study design. It also included number of participants, median age, and median body mass index (BMI, measured in kg/m²). The extracted information also included clinical stage of gastric cancer, diagnostic indicators of sarcopenia, and outcome indicators.
The researchers also extracted the diagnostic criteria used, including skeletal muscle index (SMI), hand grip strength, and 6-meter gait speed. They recorded the measurement methods for muscle mass, which included CT (computed tomography), MRI (magnetic resonance imaging), DXA, and BIA. They also recorded the cut-off points used for diagnosis.
The cut-off points for diagnosing sarcopenia varied by country:
- China: less than 34.9 cm²/m² for women and less than 40.8 cm²/m² for men
- Japan: less than 38 cm²/m² for women and less than 42 cm²/m² for men
- South Korea: less than 38.5 cm²/m² for women and less than 52.4 cm²/m² for men
The definition criteria were different across countries. The studies covered gastric cancer from early to advanced stages. Age and body weight were mostly recorded as continuous data.
When heterogeneity (differences between study results) was present, the researchers used a random-effects model for analysis. Egger's test was used to detect publication bias (the tendency for studies with positive results to be published more often).
Heterogeneity was analyzed using the Q test and the I² test. The fixed-effects model was used when P > 0.05 or I² < 50%. This model assumes that different results across studies are due to chance. The random-effects model was used when P < 0.05 or I² > 50%. This model assumes that results genuinely vary across studies.
When heterogeneity was present, the random-effects model was considered more appropriate. This model leads to wider confidence intervals and more conservative effect estimates. Publication bias was assessed by visual inspection of funnel plots. Begg's and Egger's tests were also used. Sensitivity analyses, meta-regression, and subgroup analyses were performed to further investigate heterogeneity. STATA 15.0 software was used for all statistical analyses.
How Study Quality Was Assessed
The researchers used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of each included study. This scale assesses three dimensions: selection, comparability, and exposure for case-control studies.
The quality score ranges from 0 to 9. A score of 6 or higher represents high quality. Each of the 8 items was rated as "yes," "no," "unclear," or "not applicable." Whether a study should be included or excluded was determined through group discussion.
The quality scores for all included studies were 6 or higher. Specifically:
- 1 article scored 6 points
- 11 articles scored 7 points
- 5 articles scored 8 points
- 3 articles scored 9 points
Key Finding: How Common Is Sarcopenia in Stomach Cancer?
The researchers retrieved 1,244 studies from the databases. After removing 526 duplicates, 698 reports were excluded for various reasons. These reasons included being guidelines, case reports, reviews, having ineligible control groups, incomplete presentation, or irrelevant endpoints. Finally, 20 articles were included in the analysis.
All included articles were observational studies. Nine were retrospective studies and 11 were prospective studies. The studies were conducted in China, Japan, Korea, India, Ireland, and Turkey.
Across the 20 studies, there were 4,782 cases. Of these, 1,098 cases were gastric cancer combined with sarcopenia. This gives an incidence of 26.6% (95% CI: 0.215 to 0.318). In other words, about 1 in 4 gastric cancer patients in these studies also had sarcopenia.
Risk Factor: Age
Twelve papers investigated the correlation between gastric cancer combined with sarcopenia and age. There was substantial heterogeneity among these studies (I² = 72.9%, P < 0.001). A random-effects model was used for the meta-analysis.
The results showed that gastric cancer patients over 65 years old had an increased risk of sarcopenia (OR = 1.128, 95% CI: 1.056 to 1.204, P < 0.001). An odds ratio (OR) of 1.128 means that the odds of sarcopenia were about 13% higher for each unit increase in age. The result was statistically significant, meaning there is less than a 0.1% probability that this finding was due to chance.
The multivariate analysis (which adjusts for other factors) gave similar results (OR = 1.453, 95% CI: 0.887 to 2.381). The univariate analysis (which looks at one factor at a time) also gave similar results (OR = 1.116, 95% CI: 1.035 to 1.202).
Subgroup analysis showed a risk in patients over 65 years old (OR = 1.133, 95% CI: 1.060 to 1.212, P < 0.001). The risk was even higher in patients over 75 years old (OR = 1.958, 95% CI: 1.278 to 3.001, P < 0.01).
The researchers concluded that the likelihood of sarcopenia in gastric cancer patients increased with age over 65 years, but not over 70 years.
Risk Factor: Gender
Five papers examined the association between gastric cancer combined with sarcopenia and gender. There was significant heterogeneity among these studies (I² = 68.9%, P < 0.01). A random-effects model was used for the meta-analysis.
The results indicated that the risk of sarcopenia was increased in male gastric cancer patients (OR = 1.054, 95% CI: 0.620 to 1.791, P < 0.01). The multivariate analysis (OR = 1.150, 95% CI: 0.150 to 8.827) and univariate analysis (OR = 1.105, 95% CI: 0.625 to 1.952) gave consistent results.
One study found that the prevalence of sarcopenia was 19.2% in men and 8.6% in women. The researchers noted that the Asian Working Group on Sarcopenia criteria are more suitable for Asian populations. The prevalence of sarcopenia increases with age, and males are more likely to develop it.
Potential mechanisms for sex differences in sarcopenia prevalence include the following: muscle mass decreases progressively with age in males, and this decrease is not significant or only minimal in females.
Risk Factor: Body Mass Index
Six papers investigated the correlation between gastric cancer combined with sarcopenia and body mass index (BMI). There was notable heterogeneity among these studies (I² = 71.6%, P < 0.01).
The results of the meta-analysis using a random-effects model showed that the risk of sarcopenia was greatly increased in gastric cancer patients with low BMI (OR = 1.117, 95% CI: 0.881 to 1.414, P < 0.01).
The univariate analysis suggested an increase in the risk of sarcopenia in gastric cancer patients with low BMI (OR = 1.139, 95% CI: 0.897 to 1.447). However, only 1 paper conducted a multivariate analysis (OR = 0.403, 95% CI: 0.078 to 2.082, P < 0.01). This analysis suggested that BMI is a continuous variable, and the risk of sarcopenia increases as BMI decreases.
Risk Factor: Tumor Diameter
Four papers examined the association between gastric cancer combined with sarcopenia and tumor diameter. There was marked heterogeneity among these studies (I² = 68.9%, P < 0.01). A random-effects model was used for the meta-analysis.
The results showed that the risk of sarcopenia was increased in gastric cancer patients with a tumor diameter greater than 3 cm (OR = 1.515, 95% CI: 1.021 to 2.248, P < 0.01).
The multivariate analysis (OR = 2.090, 95% CI: 1.230 to 3.551) and univariate analysis (OR = 1.344, 95% CI: 0.920 to 1.962) suggested that gastric cancer patients with larger tumors had an increased risk of sarcopenia. This suggests that a larger tumor is a risk factor for sarcopenia.
Risk Factor: Nutritional Risk
Nutritional risk screening using the NRS2002 tool was used as the scoring standard. Four papers investigated the association between gastric cancer combined with sarcopenia and nutritional risk. There was notable heterogeneity among these studies (I² = 76.2%, P < 0.01).
Using the random-effects model, the meta-analysis showed that the overall risk of sarcopenia was visibly enhanced in gastric cancer patients with an NRS score greater than 3 (OR = 3.953, 95% CI: 2.038 to 7.668, P < 0.001). This means that patients with a nutritional risk score above 3 had nearly four times the odds of having sarcopenia. This was the strongest risk factor identified in the analysis.
The multivariate analysis (OR = 3.441, 95% CI: 1.623 to 7.295) and univariate analysis (OR = 4.199, 95% CI: 1.673 to 10.540) found that the risk of sarcopenia was greatly elevated in those with higher NRS scores. This indicates that an NRS2002 score greater than 3 is a risk factor for gastric cancer combined with sarcopenia.
Factors With No Significant Link
The researchers also examined several other potential risk factors. These factors did not show a statistically significant correlation with sarcopenia in gastric cancer patients.
Tumor stage: The correlation analysis showed that a higher tumor stage was correlated with a risk of sarcopenia in gastric cancer patients (OR = 1.907, 95% CI: 0.967 to 3.763, P = 0.953). However, this result was not statistically significant.
Gastrectomy approach (type of stomach surgery): Both multivariate analysis (OR = 1.837, 95% CI: 1.237 to 2.727) and univariate analysis (OR = 1.702, 95% CI: 1.125 to 2.574) showed that the risk of sarcopenia was higher in patients undergoing total gastrectomy (complete stomach removal) than partial gastrectomy (removal of part of the stomach). However, the overall result was not statistically significant (P > 0.05).
Tumor differentiation level: The correlation analysis indicated that gastric cancer differentiation level (how abnormal the cancer cells look under a microscope) was not significantly associated with sarcopenia (OR = 0.586, 95% CI: 0.325 to 1.059, P > 0.05).
Severe adverse reactions after chemotherapy: Inflammatory indicators including NLR (neutrophil-to-lymphocyte ratio), HB (hemoglobin), and ALB (albumin) after chemotherapy were not significantly associated with sarcopenia (OR = 0.926, 95% CI: 0.793 to 1.082, P = 0.054).
The researchers noted that all these indexes with P > 0.05 (not statistically significant) should be further verified in future studies.
Understanding the Differences Between Studies
Given the high heterogeneity in the analyses, the researchers tried to find the source of the differences. Sensitivity analysis could not identify the source. The pooled risk estimates were calculated again for each study, and the results were stable.
Subgroup analysis based on regional distribution also did not find the source of heterogeneity. Egger's test confirmed that the meta-analysis results were reliable for the 20 included papers, without noticeable publication bias (P < 0.05).
Meta-regression was performed on age, sex, NRS, BMI, tumor size, tumor stage, gastrectomy method, tumor differentiation, and inflammatory indicators (NLR, HB, ALB) of adverse reactions after chemotherapy. The results showed that advanced age, high NRS score, male sex, and low BMI (P < 0.005) were positively correlated with the risk of sarcopenia in gastric cancer patients. These were significant risk factors.
The researchers discussed possible reasons for the heterogeneity. These reasons may be related to the underlying mechanisms of gastric cancer-associated sarcopenia. These mechanisms include:
- Abnormal nutrition metabolism
- Muscle atrophy caused by decreased exercise
- Mitochondrial dysfunction (problems with the energy-producing parts of cells)
- Oxidative damage
- Cytokine levels (signaling molecules of the immune system)
- Chemotherapy-induced sarcopenia, possibly due to mitochondrial damage
- Age-related hormonal changes (previous investigations found that the median age was 70 years)
- Cell apoptosis (programmed cell death)
- Ferroptosis (a type of cell death linked to iron)
Due to individual differences, the source of heterogeneity could not be clarified through the literature. The primary studies used relatively consistent definitions of sarcopenia. These definitions included BIA, DXA, and a combination of muscle mass, muscle strength, and gait speed. There are still differences in prevalence across studies. These differences may result from different methodologies, thresholds, and diagnostic approaches, leading to clinical heterogeneity.
In addition to the mechanisms above, regional differences between Asian and European populations are also a source of heterogeneity. The literature has found that genetics play a role.
What This Means for Patients
This meta-analysis shows an increased prevalence of sarcopenia in gastric cancer patients. The overall prevalence was 26.6%, meaning about 1 in 4 patients with gastric cancer also have sarcopenia.
This analysis focused on Asian populations. It suggested that high nutritional risk was a risk factor for sarcopenia in gastric cancer patients. Age over 65 years and tumor diameter over 3 cm may also be risk factors. Men may be prone to sarcopenia.
Targeting these risk factors may be beneficial in the prevention of sarcopenia in gastric cancer patients. The findings suggest that doctors should pay close attention to muscle health in gastric cancer patients, especially those who are older, male, have larger tumors, or have poor nutritional status.
The researchers emphasized that the main cause of death in gastric cancer patients may be postoperative sarcopenia rather than the cancer itself. This makes prevention and management of muscle loss a critical part of gastric cancer care.
Limitations of This Research
The researchers identified several limitations of this meta-analysis.
First, there was high heterogeneity across the included studies. The researchers could not identify the source of this heterogeneity through sensitivity analysis or subgroup analysis based on regional distribution.
Second, the definition criteria for sarcopenia were different across countries. China, Japan, and South Korea each used different cut-off points for diagnosing sarcopenia. This variation may have affected the results.
Third, the analysis focused primarily on Asian populations. The findings may not apply equally to European or other populations.
Fourth, some risk factors showed a correlation with sarcopenia in individual analyses but were not statistically significant overall. These factors include tumor stage, gastrectomy approach, tumor differentiation, and severe adverse reactions after chemotherapy. The researchers noted that these factors with P > 0.05 should be further verified in future studies.
Fifth, the mechanisms behind gastric cancer-associated sarcopenia are complex and involve many biological pathways. The researchers could not fully clarify these mechanisms from the available literature.
Recommendations
Based on the findings of this meta-analysis, the following recommendations may help patients and healthcare providers:
- Screen for sarcopenia in all gastric cancer patients, especially those over 65 years old.
- Pay special attention to male patients, who appear to have a higher risk.
- Monitor body mass index, since low BMI is associated with increased risk.
- Use the NRS2002 nutritional risk screening tool to identify patients with high nutritional risk (score greater than 3). These patients have nearly four times the odds of sarcopenia.
- Consider tumor diameter when assessing risk, since tumors larger than 3 cm are linked to higher sarcopenia risk.
- Target these risk factors in prevention strategies to reduce the burden of sarcopenia in gastric cancer patients.
The researchers concluded that targeting these risk factors may be beneficial in the prevention of sarcopenia in gastric cancer patients. Early identification of high-risk patients could allow for timely nutritional support and muscle-preserving interventions.
Frequently Asked Questions
What is sarcopenia?
Sarcopenia is a progressive muscle disease involving severe loss of muscle mass and strength. It is most often linked to aging, but can also be caused by cancer and other conditions. When another disease causes it, it is called secondary sarcopenia. It is recognized in the International Classification of Diseases (ICD-10: M62).
Who is at higher risk of sarcopenia with stomach cancer?
In this analysis, the strongest risk factor was high nutritional risk, measured by an NRS2002 score above 3, which raised the odds about fourfold. Other linked factors were age over 65, male sex, low body mass index, and tumors larger than 3 centimeters. Tumor stage, surgery type, tumor differentiation, and severe chemotherapy side effects showed no significant link.
What does a nutritional risk score above 3 mean?
A score above 3 on the NRS2002 nutritional risk screening tool was the strongest risk factor in this analysis. Patients with this score had nearly four times the odds of having sarcopenia compared with those below that threshold. This suggests that nutritional screening can help identify patients who may need closer monitoring.
Does age affect the risk of sarcopenia in stomach cancer?
Yes. In this analysis, patients over 65 had an increased risk of sarcopenia. The risk was even higher in those over 75. The researchers concluded that the likelihood of sarcopenia increased with age over 65, but not over 70. Age was one of several factors linked to higher risk.
Are men with stomach cancer more likely to develop sarcopenia?
In this analysis, male sex was linked to a higher risk of sarcopenia. One included study found the prevalence was 19.2% in men and 8.6% in women. The researchers noted that muscle mass decreases progressively with age in males, and this decrease is not significant or only minimal in females.
What can patients and doctors do about sarcopenia risk in stomach cancer?
The researchers recommend screening all gastric cancer patients for sarcopenia, especially those over 65. They suggest paying attention to male patients, monitoring body mass index, using the NRS2002 tool to identify high nutritional risk, and considering tumor diameter. Targeting these factors may help prevent sarcopenia and allow timely nutritional support.
When should a patient with gastric cancer and possible sarcopenia seek a second opinion?
A second opinion can be useful when muscle loss is suspected alongside gastric cancer, since about 1 in 4 patients with gastric cancer also have sarcopenia. It may help to review risk factors such as age over 65, male sex, low body mass index, tumors larger than 3 cm, and a nutritional risk score above 3, which raises the odds roughly fourfold. A second review can also address whether muscle health is being monitored as part of the treatment plan. Diagnostic Detectives Network provides independent expert second opinions.
Source Information
Original article title: Incidence and risk factors of sarcopenia in gastric cancer patients: a meta-analysis and systematic review.
Authors: Fu M, Wang X, Zhou J, Wang J.
Author affiliations: Qinghai University Affiliated Hospital (School of Clinical Medicine), Qinghai University, Qinghai Xining, China; Department of Gastroenterology, Qinghai University Affiliated Hospital, Qinghai Xining, China
Journal: BMC Cancer (2025) 25:711
DOI: https://doi.org/10.1186/s12885-025-13766-0
Registration: International Prospective Register of Systematic Reviews (No. CRD42023446996)
This patient-friendly article is based on peer-reviewed research.
