Opportunistic CT screening for osteosarcopenia predicts reduced overall survival in patients with gastric cancer: a retrospective cohort study

Introduction

Gastric cancer is the fifth most prevalent malignancy worldwide, drawing significant attention due to its persistently high incidence and mortality (1). Recent advancements in novel approaches, such as conversion therapy, have expanded treatment options and improved clinical outcomes for patients. Epidemiological studies indicate a gradual decline in gastric cancer incidence within China; however, its high mortality remains a challenge (2). Accumulating evidence highlights the critical role of treatment regimens, such as adjuvant chemotherapy, in influencing the survival outcomes of patients with gastric cancer (3). Concurrently, nutritional assessments, such as the patient-generated subjective global assessment (PG-SGA), and nutritional-inflammatory markers like the prognostic nutritional index (PNI), have been demonstrated to possess significant prognostic value in this patient population (4,5). Therefore, the selection of optimal treatment modalities is critical for determining patient prognosis and necessitates a comprehensive evaluation of patient characteristics, including cancer stage, histological type, nutritional status, and systemic comorbidities (6).

Sarcopenia, characterized by systemic loss of skeletal muscle mass, has been increasingly recognized in recent years as a predictor of poor prognosis in cancer patients (7). Similarly, emerging evidence suggests that osteoporosis may also affect clinical outcomes in this population (8). These associations may be attributed to malnutrition, cancer cachexia, and tumor-related inflammatory responses (9,10). Recently, a metabolic syndrome termed “osteosarcopenia” has garnered research interest, presenting concurrent reductions in both muscle mass and bone mineral density (BMD), potentially serving as a prognostic indicator (11). Current investigations have explored the prognostic implications of osteosarcopenia in various malignancies, including gastric cancer (12). Preliminary findings suggest that osteosarcopenia may predict unfavorable clinical outcomes (13). However, previous studies have been limited by small-scale cohorts or specific cancer stages. Furthermore, few studies have compared the prognostic value of osteosarcopenia against isolated sarcopenia or osteoporosis. Consequently, whether the assessment of bone offers additional prognostic value beyond muscle remains controversial. Notably, literature highlights the feasibility of sarcopenia and osteoporosis screening through routine computed tomography (CT) imaging (14,15).

Therefore, this study aims to utilize routine abdominal CT scans for osteosarcopenia identification and investigate its association with prognosis in gastric cancer patients across broader cancer stages. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-942/rc).

Methods

Patients

We retrospectively reviewed 1,394 patients diagnosed with gastric cancer at The First Affiliated Hospital of Guangxi Medical University between 2019 and 2024. The inclusion criteria for this study were: (I) age ≥18 years; (II) hospitalization for more than 48 hours; (III) histologically confirmed gastric cancer; (IV) received first surgical treatment for gastric cancer at The First Affiliated Hospital of Guangxi Medical University. Exclusion criteria included: (I) organ transplant recipients; (II) women during pregnancy; (III) diagnosed with human immunodeficiency virus infection or with acquired immunodeficiency syndrome; (IV) admitted to the intensive care unit on admission; (V) combination of cancers in other parts of the body; (VI) key information missing. A total of 137 patients were excluded due to histologically confirmed gastrointestinal stromal tumor, 1 patient was excluded due to confirmed as gastric stump cancer, 180 patients were excluded due to incomplete clinical data, 120 patients were excluded due to incomplete histological data, and 118 patients were excluded due to the unavailability of preoperative CT scans at our hospital. Finally, 838 patients were enrolled in this study (Figure 1). All patients underwent preoperative evaluations, including blood tests, gastroscopy, and routine abdominal CT scans. Cancer staging was determined according to the 8th edition of the American Joint Committee on Cancer’s Cancer Staging Manual. All patients were followed via telephone interview and hospital visit review.

Figure 1 Patients’ flowchart. Starting from 1,394 potential patients, subsequent exclusions due to diagnosis of gastrointestinal stromal tumor or gastric stump cancer, and unavailable data yielded the final analytical sample of 838 patients.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The First Affiliated Hospital of Guangxi Medical University (No. 2025-E0775). Informed consent was waived due to the nature of the retrospective study.

Definition of sarcopenia, osteoporosis, and osteosarcopenia

Preoperative non-contrast abdominal CT images were retrieved from the hospital’s digital imaging system in Digital Imaging and Communications in Medicine (DICOM) format and loaded into the 3D Slicer software (version 5.6, http://www.slicer.org) to assess body composition.

Sarcopenia was defined as a reduced skeletal muscle index (SMI) at the third lumbar vertebra (L3) level (Figure 2). Hounsfield unit (HU) window thresholds were set to −29 to 150 for skeletal muscle identification. Axial CT images at L3 were analyzed using semi-automatic segmentation. SMI was calculated using the formula: cross-sectional skeletal muscle area at L3 (cm²)/height squared (m²) (16). Due to the current lack of recognized L3-SMI cut-off values, the X-TILE (17,18) was used to determine the optimal gender-specific SMI cut-off values in this study. The gender-specific cutoff values of SMI were 48.2 cm²/m² for males and 37.6 cm²/m² for females according to X-tile software (version 3.6.1; Yale University).

Figure 2 CT images for (A) normal, (B) osteoporosis, (C) sarcopenia and (D) osteosarcopenia patients with gastric cancer. The red contour denotes the L3-level skeletal muscle area, while the green contour denotes the L1-level trabecular bone area used for bone mineral density measurement. CT, computed tomography.

Osteoporosis was defined as reduced BMD at the first lumbar vertebra (L1) level (Figure 2). An oval region of interest (ROI) was manually delineated in the L1 vertebral body on axial CT images, and BMD was assessed by examining the average HU within the oval ROI (19). The cutoff values of BMD were 160 for both males and females according to a published report (15).

Osteosarcopenia was defined as the coexistence of sarcopenia and osteoporosis (20).

Systemic inflammatory indices

The composite inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), PNI, and systemic immune-inflammation index (SII), were used to assess the systemic inflammatory response and nutritional status of the patients. The NLR was calculated as neutrophil count (×10⁹/L) divided by the lymphocyte count (×10⁹/L). The PNI was calculated as serum albumin level (g/L) + 5 × lymphocyte count (×10⁹/L). The SII was calculated as platelet count (×10⁹/L) × neutrophil count (×10⁹/L)/lymphocyte count (×10⁹/L). According to previous literature, the cutoff values for NLR, PNI, and SII were set at 3, 40, and 395, respectively (21-23).

Nutritional assessment

PG-SGA was utilized to evaluate the nutritional status of patients. PG-SGA assessments were completed within 24 hours of hospital admission. A total score of ≥4 was defined as malnutrition requiring clinical intervention, consistent with established criteria (24).

Statistical analysis

Categorical variables are presented as frequencies (percentages), and continuous variables are expressed as medians (interquartile ranges, IQR) or means ± standard deviations (SD) based on data distribution.

Associations between the osteosarcopenia and variables were analyzed using chi-square tests or Fisher’s exact tests for categorical variables, and the Shapiro-Wilk test or Mann-Whitney U tests for continuous variables.

Overall survival (OS) was defined as the interval from surgery to death or the final follow-up. Kaplan-Meier curves were generated to compare survival outcomes between subgroups, and prognostic differences were analyzed using the log-rank test.

Prognostic factors were determined using univariate Cox proportional hazards regression. Subsequently, a multivariate analysis for OS was performed using the forced entry method. The final model included all factors that were significant (P<0.05) in the univariate analysis, while also forcing the inclusion of clinically relevant factors for adjustment. Hazard ratio (HR) and 95% confidence interval (CI) were reported.

All analyses were performed using SPSS Statistics (version 26; IBM Corp.) and Python (version 3.13; Python Software Foundation), with a two-sided P<0.05 considered statistically significant.

Results

Clinical characteristics

The clinical characteristics of the 838 patients included in this study are summarized in Table 1. The study included 533 (63.8%) males and 303 (36.2%) females with a mean age of 57.08±11.30. Robotic, laparoscopic, and open surgeries were performed in 207 (24.7%), 564 (67.3%), and 67 (8.0%) patients, respectively. According to the postoperative pathology reports, 742 (88.5%) patients had adenocarcinomas, and 96 (11.5%) patients had other types of histopathology. In addition, 232 (27.7%), 197 (23.5%), 350 (41.8%), and 59 (7.0%) patients had cancer stages I, II, III, and IV, respectively. 493 (58.8%) patients received adjuvant chemotherapy. For tumor indicators, the median alpha fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) were 2.37 (quartiles, 1.73–3.28) ng/mL, 2.26 (quartiles, 1.41–3.87) ng/mL and 6.13 (quartiles, 2.35–16.46) U/mL, respectively. Regarding the composite inflammatory index, the median NLR was 1.96 (quartiles, 1.47–2.70), the mean of PNI was 45.46±5.48, and the median SII was 542.14 (quartiles, 360.82–821.08). In terms of nutritional status, the mean body mass index (BMI) was 22.21±3.18 kg/m², the mean PG-SGA score was 5.50±3.92, and the mean albumin (ALB) was 36.55±3.97 g/L; 142 (16.9%) patients were diagnosed as osteosarcopenia.

Association between osteosarcopenia and variables

Osteosarcopenia was significantly correlated with gender, age, chemotherapy, PNI, BMI, PG-SGA and ALB (P values of 0.03, <0.001, 0.002, <0.001, <0.001, <0.001 and 0.003, Table 2). In contrast, osteosarcopenia was not significantly correlated with surgical approach, histological type, cancer stage, AFP, CEA, CA199, NLR or SII (P values of 0.37, 0.35, 0.38, 0.41, 0.21, 0.90, 0.20 and 0.95, Table 2).

Univariate analysis

The median OS was 18 months for all 838 patients in this study cohort, with 20 months in the normal group, 17 months in the osteoporosis-only group, 15 months in the sarcopenia-only group, and 16 months in the osteosarcopenia group. Kaplan-Meier curves demonstrated that patients with osteoporosis, sarcopenia or osteosarcopenia had worse survival outcomes than the normal (P values of 0.006, 0.003 and <0.001, Figure 3). The osteosarcopenia group showed worse OS than the osteoporosis-only group (P=0.03), while there was no difference compared with the sarcopenia-only group (P=0.28). The univariate analysis indicated that gender (male vs. female), age (≥70 vs. <70, years), surgical approach (open surgery vs. robotic or laparoscopic surgery), cancer stage, CEA (>5 vs. ≤5, ng/mL), CA199 (>37 vs. ≤37, U/mL), PNI (<40 vs. ≥40), PG-SGA(≥4 vs. <4, points), osteoporosis, sarcopenia and osteosarcopenia were significantly correlated with OS (P values of 0.01, <0.001, 0.001, <0.001, 0.01, <0.001, 0.02, <0.001, 0.008, 0.005 and <0.001, Table 3).

Figure 3 Kaplan-Meier plot of overall survival by osteosarcopenia, sarcopenia and osteosarcopenia. Kaplan-Meier survival curves for the normal group (green line), the osteoporosis-only group (blue line), the sarcopenia-only group (orange line) and the osteosarcopenia group (red line). P values were calculated using the log-rank test.

Multivariable analysis

Based on the results of univariate COX regression analysis, gender, age, surgical approach, cancer stage, CEA, CA199, PNI, PG-SGA, osteoporosis, sarcopenia and osteosarcopenia were included in the multivariate COX regression analysis. Chemotherapy was included as a clinically relevant factor to adjust for potential bias. The multivariate analysis demonstrated that cancer stage (II: HR =2.973, 95% CI: 1.274–6.937, P=0.01; III: HR =7.133, 95% CI: 3.300–15.415, P<0.001; IV: HR =10.390, 95% CI: 3.641–29.651, P<0.001), chemotherapy (HR =0.491, 95% CI: 0.311–0.776, P=0.002), CA199 (HR =1.634, 95% CI: 1.020–2.617, P=0.041), PG-SGA (HR =1.939, 95% CI: 1.158–3.247, P=0.01), osteoporosis (HR =1.785, 95% CI: 1.019–3.126, P=0.043) and osteosarcopenia (HR =2.291, 95% CI: 1.238–4.239, P=0.008) were associated with patient prognosis (Table 3).

Discussion

In this study, we investigated body composition changes by routine abdominal CT to analyze the effect of osteosarcopenia on the prognosis of gastric cancer patients undergoing surgical treatment. We found that osteosarcopenia diagnosed by opportunistic screening was strongly associated with preoperative nutritional status and postoperative survival outcome in gastric cancer patients. This is a clinical prognostic study with a large sample covering multiple cancer stages, and this study suggests that routine abdominal CT used for other examination purposes can also be used to screen for osteosarcopenia as one of the markers of preoperative nutritional intervention in gastric cancer patients.

Gastric cancer patients often suffer malabsorption and malnutrition due to cancer load, which may lead to the development of osteosarcopenia. In this study, nutritional evaluation indicators such as PNI, BMI, PG-SGA and ALB in the osteosarcopenia group performed worse than those in the control group. Previously, it has been reported that patients with osteosarcopenia have worse BMI and PNI performance (25-27), which is consistent with the findings of the present study and suggests that nutritional therapy is necessary for patients diagnosed with osteosarcopenia. We also found that the osteosarcopenia group exhibited significantly poorer scores in the PG-SGA—a validated nutritional assessment tool for cancer patients—and lower ALB compared to the control group. These findings further suggest that gastric cancer patients with osteosarcopenia may require more urgent nutritional interventions. In addition, 16.9% of patients in our study cohort were diagnosed with osteosarcopenia. In other reports, the prevalence of osteosarcopenia ranged from 12–33% in multiple cancers (26,28,29). Those findings suggest that osteosarcopenia is prevalent in patients with malignant tumors; however, current studies of body composition have focused on sarcopenia, and therefore, attention should be paid to analyzing a broader range of body components, such as bone or fat. In this study, routine abdominal CT was utilized to identify patients with osteosarcopenia without increasing the burden of hospitalization, which we believe could be a convenient screening method.

The results of this study suggest that osteosarcopenia is strongly associated with poorer OS of gastric cancer patients. This is consistent with previous findings reported by Hirase et al., regarding studies on osteosarcopenia and prognosis of gastric cancer (12). In addition, researchers have also found that multiple malignant tumors patients with combined osteosarcopenia tend to have a worse prognosis (25,26), which is consistent with the main findings of this study, suggesting that screening for osteosarcopenia in patients with malignant tumors has potential value in improving the prognosis of patients. Crucially, after adjusting for confounding factors, multivariate analysis revealed that osteoporosis alone was associated with poor OS. When comparing the different body composition phenotypes, we found that the HR for osteosarcopenia was the highest, surpassing both sarcopenia and osteoporosis alone. This indicates that the combined phenotype exerts a more detrimental impact on prognosis than sarcopenia or osteoporosis alone. Therefore, our results suggest that bone assessment could provide additive prognostic value beyond muscle assessment alone.

The management of osteosarcopenia necessitates a multimodal approach integrating nutritional, exercise-based and pharmacological interventions (30). Although completely reversing muscle or bone loss in gastric cancer patients within a short timeframe remains challenging, opportunistic CT screening for osteosarcopenia provides benefits in clinical practice. First, this screening serves as a reference for risk stratification. Identifying patients with osteosarcopenia allows clinicians to adjust treatment plans, such as modifying chemotherapy plans and developing more rigorous fall prevention protocols for frail patients. Moreover, early screening and diagnosis act as a starting point for long-term rehabilitation. In the perioperative period, identifying osteosarcopenia allows for the immediate implementation of nutritional support to address muscle loss, while simultaneously initiating long-term pharmacological interventions for osteoporosis (31,32). This approach could help in improving postoperative recovery, survival outcomes, and quality of life. However, the efficacy of these interventions in oncological populations in the context of osteosarcopenia requires further validation through prospective clinical trials. Future research should focus on optimizing combined treatment protocols to target both sarcopenia and osteoporosis, thereby improving survival outcomes and quality of life in patients with malignancies.

There are several limitations to this study. First, it was a single-center study. In addition, a large population was excluded due to unavailable information. Therefore, larger, multicenter, high-quality randomized controlled studies are needed to validate our findings.

Conclusions

In conclusion, our study suggests that osteosarcopenia is a valuable predictor of prognosis in patients with gastric cancer, and routine abdominal CT, as a convenient means of opportunistic screening, should be promoted in clinical practice for osteosarcopenia identification.

Acknowledgments

We would like to thank Yitong Chen (Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China) for his valuable help.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-942/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-942/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-942/prf

Funding: This study was supported by the Pandeng Plan of The First Affiliated Hospital of Guangxi Medical University (No. YYZS2023007), and Natural Science Foundation of Guangxi (Nos. 2024JJA140624 and 2025JJA140026).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-942/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The First Affiliated Hospital of Guangxi Medical University (No. 2025-E0775). Informed consent was waived due to the nature of the retrospective study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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